Requirement for Parp-1 and DNA ligases 1 or 3 but not of Xrcc1 in chromosomal translocation formation by backup end joining

PubMed Central

Soni, Aashish; Siemann, Maria; Grabos, Martha; Murmann, Tamara; Pantelias, Gabriel E.; Iliakis, George

2014-01-01

In mammalian cells, ionizing radiation (IR)-induced DNA double-strand breaks (DSBs) are repaired in all phases of the cell cycle predominantly by classical, DNA-PK-dependent nonhomologous end joining (D-NHEJ). Homologous recombination repair (HRR) is functional during the S- and G2-phases, when a sister chromatid becomes available. An error-prone, alternative form of end joining, operating as backup (B-NHEJ) functions robustly throughout the cell cycle and particularly in the G2-phase and is thought to backup predominantly D-NHEJ. Parp-1, DNA-ligases 1 (Lig1) and 3 (Lig3), and Xrcc1 are implicated in B-NHEJ. Chromosome and chromatid translocations are manifestations of erroneous DSB repair and are crucial culprits in malignant transformation and IR-induced cell lethality. We analyzed shifts in translocation formation deriving from defects in D-NHEJ or HRR in cells irradiated in the G2-phase and identify B-NHEJ as the main DSB repair pathway backing up both of these defects at the cost of a large increase in translocation formation. Our results identify Parp-1 and Lig1 and 3 as factors involved in translocation formation and show that Xrcc1 reinforces the function of Lig3 in the process without being required for it. Finally, we demonstrate intriguing connections between B-NHEJ and DNA end resection in translocation formation and show that, as for D-NHEJ and HRR, the function of B-NHEJ facilitates the recovery from the G2-checkpoint. These observations advance our understanding of chromosome aberration formation and have implications for the mechanism of action of Parp inhibitors. PMID:24748665

Requirement for Parp-1 and DNA ligases 1 or 3 but not of Xrcc1 in chromosomal translocation formation by backup end joining.

PubMed

Soni, Aashish; Siemann, Maria; Grabos, Martha; Murmann, Tamara; Pantelias, Gabriel E; Iliakis, George

2014-06-01

In mammalian cells, ionizing radiation (IR)-induced DNA double-strand breaks (DSBs) are repaired in all phases of the cell cycle predominantly by classical, DNA-PK-dependent nonhomologous end joining (D-NHEJ). Homologous recombination repair (HRR) is functional during the S- and G2-phases, when a sister chromatid becomes available. An error-prone, alternative form of end joining, operating as backup (B-NHEJ) functions robustly throughout the cell cycle and particularly in the G2-phase and is thought to backup predominantly D-NHEJ. Parp-1, DNA-ligases 1 (Lig1) and 3 (Lig3), and Xrcc1 are implicated in B-NHEJ. Chromosome and chromatid translocations are manifestations of erroneous DSB repair and are crucial culprits in malignant transformation and IR-induced cell lethality. We analyzed shifts in translocation formation deriving from defects in D-NHEJ or HRR in cells irradiated in the G2-phase and identify B-NHEJ as the main DSB repair pathway backing up both of these defects at the cost of a large increase in translocation formation. Our results identify Parp-1 and Lig1 and 3 as factors involved in translocation formation and show that Xrcc1 reinforces the function of Lig3 in the process without being required for it. Finally, we demonstrate intriguing connections between B-NHEJ and DNA end resection in translocation formation and show that, as for D-NHEJ and HRR, the function of B-NHEJ facilitates the recovery from the G2-checkpoint. These observations advance our understanding of chromosome aberration formation and have implications for the mechanism of action of Parp inhibitors. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Immunoprotective properties of recombinant LigA and LigB in a hamster model of acute leptospirosis

PubMed Central

Lourdault, Kristel; Matsunaga, James; Haake, David A.

2017-01-01

Leptospirosis is the most widespread zoonosis and is considered a major public health problem worldwide. Currently, there is no widely available vaccine against leptospirosis for use in humans. A purified, recombinant subunit vaccine that includes the last six immunoglobulin-like (Ig-like) domains of the leptospiral protein LigA (LigA7’-13) protects against lethal infection but not renal colonization after challenge by Leptospira interrogans. In this study, we examined whether the addition of the first seven Ig-like domains of LigB (LigB0-7) to LigA7’-13, can enhance immune protection and confer sterilizing immunity in the Golden Syrian hamster model of acute leptospirosis. Hamsters were subcutaneously immunized with soluble, recombinant LigA7’-13, LigB0-7, or a combination of LigA7’-13 and LigB0-7 in Freund’s adjuvant. Immunization with Lig proteins generated a strong humoral immune response with high titers of IgG that recognized homologous protein, and cross-reacted with the heterologous protein as assessed by ELISA. LigA7’-13 alone, or in combination with LigB0-7, protected all hamsters from intraperitoneal challenge with a lethal dose of L. interrogans serovar Copenhageni strain Fiocruz L1-130. However, bacteria were recovered from the kidneys of all animals. Of eight animals immunized with LigB0-7, only three survived Leptospira challenge, one of which lacked renal colonization and had antibodies to native LigB by immunoblot. In addition, sera from two of the three LigB0-7 immunized survivors cross-reacted with LigA11-13, a region of LigA that is sufficient for protection. In summary, we confirmed that LigA7’-13 protects hamsters from death but not infection, and immunization with LigB0-7, either alone or in combination with LigA7’-13, did not confer sterilizing immunity. PMID:28704385

Low levels of endogenous or X-ray-induced DNA double-strand breaks activate apoptosis in adult neural stem cells.

PubMed

Barazzuol, Lara; Rickett, Nicole; Ju, Limei; Jeggo, Penny A

2015-10-01

The embryonic neural stem cell compartment is characterised by rapid proliferation from embryonic day (E)11 to E16.5, high endogenous DNA double-strand break (DSB) formation and sensitive activation of apoptosis. Here, we ask whether DSBs arise in the adult neural stem cell compartments, the sub-ventricular zone (SVZ) of the lateral ventricles and the sub-granular zone (SGZ) of the hippocampal dentate gyrus, and whether they activate apoptosis. We used mice with a hypomorphic mutation in DNA ligase IV (Lig4(Y288C)), ataxia telangiectasia mutated (Atm(-/-)) and double mutant Atm(-/-)/Lig4(Y288C) mice. We demonstrate that, although DSBs do not arise at a high frequency in adult neural stem cells, the low numbers of DSBs that persist endogenously in Lig4(Y288C) mice or that are induced by low radiation doses can activate apoptosis. A temporal analysis shows that DSB levels in Lig4(Y288C) mice diminish gradually from the embryo to a steady state level in adult mice. The neonatal SVZ compartment of Lig4(Y288C) mice harbours diminished DSBs compared to its differentiated counterpart, suggesting a process selecting against unfit stem cells. Finally, we reveal high endogenous apoptosis in the developing SVZ of wild-type newborn mice. © 2015. Published by The Company of Biologists Ltd.

Comparative evaluation of recombinant LigB protein and heat-killed antigen-based latex agglutination test with microscopic agglutination test for diagnosis of bovine leptospirosis.

PubMed

Nagalingam, Mohandoss; Thirumalesh, Sushma Rahim Assadi; Kalleshamurthy, Triveni; Niharika, Nakkala; Balamurugan, Vinayagamurthy; Shome, Rajeswari; Sengupta, Pinaki Prasad; Shome, Bibek Ranjan; Prabhudas, Krishnamsetty; Rahman, Habibur

2015-10-01

This study aimed to develop latex agglutination test (LAT) using recombinant leptospiral immunoglobulin-like protein (LigB) (rLigB) antigen and compare its diagnostic efficacy with LAT using conventional heat-killed leptospiral antigen and microscopic agglutination test (MAT) in diagnosing bovine leptospirosis. The PCR-amplified 1053-bp ligB gene sequences from Leptospira borgpetersenii Hardjo serovar were cloned in pET 32 (a) vector at EcoRI and NotI sites and expressed in BL21 E. coli cells as fusion protein with thioredoxin (-57 kDa) and characterized by SDS-PAGE and immunoblot. Out of 390 serum samples [cattle (n = 214), buffaloes (n = 176)] subjected to MAT, 115 samples showed reciprocal titre≥100 up to 1600 against one or more serovars. For recombinant LigB protein/antigen-based LAT, agglutination was observed in the positive sample, while no agglutination was observed in the negative sample. Similarly, heat-killed leptospiral antigen was prepared from and used in LAT for comparison with MAT. A two-sided contingency table was used for analysis of LAT using both the antigens separately against MAT for 390 serum samples. The sensitivity, specificity and positive and negative predictive values of recombinant LigB LAT were found to be 75.65, 91.27, 78.38 and 89.96 %, respectively, and that of heat-killed antigen-based LAT were 72.17, 89.82, 74.77 and 88.53 %, respectively, in comparison with MAT. This developed test will be an alternative/complementary to the existing battery of diagnostic assays/tests for specific detection of pathogenic Leptospira infection in bovine population.

Pathogenic Leptospira species express surface-exposed proteins belonging to the bacterial immunoglobulin superfamily

PubMed Central

Matsunaga, James; Barocchi, Michele A.; Croda, Julio; Young, Tracy A.; Sanchez, Yolanda; Siqueira, Isadora; Bolin, Carole A.; Reis, Mitermayer G.; Riley, Lee W.; Haake, David A.; Ko, Albert I.

2005-01-01

Summary Proteins with bacterial immunoglobulin-like (Big) domains, such as the Yersinia pseudotuberculosis invasin and Escherichia coli intimin, are surface-expressed proteins that mediate host mammalian cell invasion or attachment. Here, we report the identification and characterization of a new family of Big domain proteins, referred to as Lig (leptospiral Ig-like) proteins, in pathogenic Leptospira. Screening of L. interrogans and L. kirschneri expression libraries with sera from leptospirosis patients identified 13 lambda phage clones that encode tandem repeats of the 90 amino acid Big domain. Two lig genes, designated ligA and ligB, and one pseudo-gene, ligC, were identified. The ligA and ligB genes encode amino-terminal lipoprotein signal peptides followed by 10 or 11 Big domain repeats and, in the case of ligB, a unique carboxy-terminal non-repeat domain. The organization of ligC is similar to that of ligB but contains mutations that disrupt the reading frame. The lig sequences are present in pathogenic but not saprophytic Leptospira species. LigA and LigB are expressed by a variety of virulent leptospiral strains. Loss of Lig protein and RNA transcript expression is correlated with the observed loss of virulence during culture attenuation of pathogenic strains. High-pressure freeze substitution followed by immunocytochemical electron microscopy confirmed that the Lig proteins were localized to the bacterial surface. Immunoblot studies with patient sera found that the Lig proteins are a major antigen recognized during the acute host infection. These observations demonstrate that the Lig proteins are a newly identified surface protein of pathogenic Leptospira, which by analogy to other bacterial immunoglobulin superfamily virulence factors, may play a role in host cell attachment and invasion during leptospiral pathogenesis. PMID:12890019

Pathogenic Leptospira species express surface-exposed proteins belonging to the bacterial immunoglobulin superfamily.

PubMed

Matsunaga, James; Barocchi, Michele A; Croda, Julio; Young, Tracy A; Sanchez, Yolanda; Siqueira, Isadora; Bolin, Carole A; Reis, Mitermayer G; Riley, Lee W; Haake, David A; Ko, Albert I

2003-08-01

Proteins with bacterial immunoglobulin-like (Big) domains, such as the Yersinia pseudotuberculosis invasin and Escherichia coli intimin, are surface-expressed proteins that mediate host mammalian cell invasion or attachment. Here, we report the identification and characterization of a new family of Big domain proteins, referred to as Lig (leptospiral Ig-like) proteins, in pathogenic Leptospira. Screening of L. interrogans and L. kirschneri expression libraries with sera from leptospirosis patients identified 13 lambda phage clones that encode tandem repeats of the 90 amino acid Big domain. Two lig genes, designated ligA and ligB, and one pseudogene, ligC, were identified. The ligA and ligB genes encode amino-terminal lipoprotein signal peptides followed by 10 or 11 Big domain repeats and, in the case of ligB, a unique carboxy-terminal non-repeat domain. The organization of ligC is similar to that of ligB but contains mutations that disrupt the reading frame. The lig sequences are present in pathogenic but not saprophytic Leptospira species. LigA and LigB are expressed by a variety of virulent leptospiral strains. Loss of Lig protein and RNA transcript expression is correlated with the observed loss of virulence during culture attenuation of pathogenic strains. High-pressure freeze substitution followed by immunocytochemical electron microscopy confirmed that the Lig proteins were localized to the bacterial surface. Immunoblot studies with patient sera found that the Lig proteins are a major antigen recognized during the acute host infection. These observations demonstrate that the Lig proteins are a newly identified surface protein of pathogenic Leptospira, which by analogy to other bacterial immunoglobulin superfamily virulence factors, may play a role in host cell attachment and invasion during leptospiral pathogenesis.

The Last Interglacial History of the Antarctic Ice sheet

NASA Astrophysics Data System (ADS)

Bradley, Sarah; Siddall, Mark; Milne, Glenn A.; Masson-Delmotte, Valerie; Wolff, Eric; Hindmarsh, Richard C. A.

2014-05-01

In this paper we present a summary of the work which was conducted as part of the 'PAST4FUTURE -WP4.1: Sea Level and Ice sheets' project. The overall aim of this study was to understand the response of the Antarctic Ice sheet (AIS) to climate forcing during the Last interglacial (LIG) and its contribution to the observed higher than present sea level during this period. The study involved the application and development of a novel technique which combined East Antarctic stable isotope ice core data with the output from a Glacial Isostatic Adjustment (GIA) model [Bradley et al., 2012]. We investigated if the stable isotope ice core data are sensitive to detecting isostatically driven changes in the surface elevation driven by changes in the ice-loading history of the AIS and if so, could we address some key questions relating to the LIG history of the AIS. Although it is believed that the West Antarctic Ice sheet (WAIS) reduced in size during the LIG compared to the Holocene, major uncertainties and unknowns remain unresolved: Did the WAIS collapse? What would the contribution of such a collapse be the higher than present LIG eustatic sea level (ESL)? We will show that a simulated collapse of the WAIS does not generate a significant elevation driven signal at the EAIS LIG ice core sites, and as such, these ice core records cannot be used to assess WAIS stability over this period. However, we will present 'treasure maps' [Bradley et al., 2012] to identify regions of the AIS where results from geological studies and/or new paleoclimate data may be sensitive to detecting a WAIS collapse. These maps can act as a useful tool for the wider science community/field scientists as a guide to highlight sites suitable to constrain the evolution of the WAIS during the LIG. Studies have proposed that the surface temperature across the East Antarctic Ice Sheet (EAIS) was significantly warmer, 2-5°C during the LIG compared to present [Lang and Wolff, 2011]. These higher temperatures are estimated primarily using the difference in the δD peak in the LIG stable isotope ice core data relative to the records for the present interglacial; a feature which is referred to as the 'LIG overshoot'. Generally studies have attributed most of this signal to changes in the Antarctic climate [Masson-Delmotte et al., 2011]. However, a previously overlooked contribution is the influence of changes in surface elevation driven by changes in ice-loading history of the EAIS [Bradley et al., 2013]. We will show that introducing a relatively moderate reduction in the amount of thickening of the EAIS over the LIG, can generate a significant elevation driven δD signal at the EAIS ice core sites, and as such elevation effects can account for a significant fraction of the LIG overshoot. We will conclude that the potential contribution of this process must be considered when using the EAIS stable isotope ice core data to make estimated of the LIG surface temperature. Finally, we will provide estimates of the contribution of the AIS to both ESL and to the higher than observed relative sea level during the LIG. Bradley, S. L., M. Siddall, G. A. Milne, V. Masson-Delmotte, and E. Wolff (2012), Where might we find evidence of a Last Interglacial West Antarctic Ice Sheet collapse in Antarctic ice core records?, Global and Planetary Change, 88-89(0), 64-75. Bradley, S. L., M. Siddall, G. A. Milne, V. Masson-Delmotte, and E. Wolff (2013), Combining ice core records and ice sheet models to explore the evolution of the East Antarctic Ice sheet during the Last Interglacial period, Global and Planetary Change, 100, 278-290. Lang, N., and E. W. Wolff (2011), Interglacial and glacial variability from the last 800 ka in marine, ice and terrestrial archives, Clim. Past., 7(2), 361-380. Masson-Delmotte, V., et al. (2011), A comparison of the present and last interglacial periods in six Antarctic ice cores, Clim. Past., 7(2), 397-423.

Degradation of lignin β-aryl ether units in Arabidopsis thaliana expressing LigD , LigF and LigG from Sphingomonas paucimobilis SYK-6

DOE PAGES

Mnich, Ewelina; Vanholme, Ruben; Oyarce, Paula; ...

2016-10-24

Here, lignin is a major polymer in the secondary plant cell wall and composed of hydrophobic interlinked hydroxyphenylpropanoid units. The presence of lignin hampers conversion of plant biomass into biofuels; plants with modified lignin are therefore being investigated for increased digestibility. The bacterium Sphingomonas paucimobilis produces lignin-degrading enzymes including LigD, LigF and LigG involved in cleaving the most abundant lignin interunit linkage, the β-aryl ether bond. In this study, we expressed the LigD, LigF and LigG ( LigDFG) genes in Arabidopsis thaliana to introduce postlignification modifications into the lignin structure. The three enzymes were targeted to the secretory pathway. Phenolicmore » metabolite profiling and 2D HSQC NMR of the transgenic lines showed an increase in oxidized guaiacyl and syringyl units without concomitant increase in oxidized β-aryl ether units, showing lignin bond cleavage. Saccharification yield increased significantly in transgenic lines expressing LigDFG, showing the applicability of our approach. Additional new information on substrate specificity of the LigDFG enzymes is also provided.« less

Degradation of lignin β-aryl ether units in Arabidopsis thaliana expressing LigD , LigF and LigG from Sphingomonas paucimobilis SYK-6

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mnich, Ewelina; Vanholme, Ruben; Oyarce, Paula

Here, lignin is a major polymer in the secondary plant cell wall and composed of hydrophobic interlinked hydroxyphenylpropanoid units. The presence of lignin hampers conversion of plant biomass into biofuels; plants with modified lignin are therefore being investigated for increased digestibility. The bacterium Sphingomonas paucimobilis produces lignin-degrading enzymes including LigD, LigF and LigG involved in cleaving the most abundant lignin interunit linkage, the β-aryl ether bond. In this study, we expressed the LigD, LigF and LigG ( LigDFG) genes in Arabidopsis thaliana to introduce postlignification modifications into the lignin structure. The three enzymes were targeted to the secretory pathway. Phenolicmore » metabolite profiling and 2D HSQC NMR of the transgenic lines showed an increase in oxidized guaiacyl and syringyl units without concomitant increase in oxidized β-aryl ether units, showing lignin bond cleavage. Saccharification yield increased significantly in transgenic lines expressing LigDFG, showing the applicability of our approach. Additional new information on substrate specificity of the LigDFG enzymes is also provided.« less

Acquisition of negative complement regulators by the saprophyte Leptospira biflexa expressing LigA or LigB confers enhanced survival in human serum

PubMed Central

Castiblanco-Valencia, Mónica M.; Fraga, Tatiana R.; Breda, Leandro C.D.; Vasconcellos, Sílvio A.; Figueira, Cláudio P.; Picardeau, Mathieu; Wunder, Elsio; Ko, Albert I.; Barbosa, Angela S.; Isaac, Lourdes

2017-01-01

Leptospiral immunoglobulin-like (Lig) proteins are surface exposed molecules present in pathogenic but not in saprophytic Leptospira species. We have previously shown that Lig proteins interact with the soluble complement regulators Factor H (FH), FH like-1 (FHL-1), FH related-1 (FHR-1) and C4b Binding Protein (C4BP). In this study, we used the saprophyte L. biflexa serovar Patoc as a surrogate host to address the specific role of LigA and LigB proteins in leptospiral complement evasion. L. biflexa expressing LigA or LigB was able to acquire FH and C4BP. Bound complement regulators retained their cofactor activities of FI in the proteolytic cleavage of C3b and C4b. Moreover, heterologous expression of ligA and ligB genes in the saprophyte L. biflexa enhanced bacterial survival in human serum. Complement deposition on lig-transformed L. biflexa was assessed by flow cytometry analysis. With regard to MAC deposition, L. biflexa expressing LigA or LigB presented an intermediate profile: MAC deposition levels were greater than those found in the pathogenic L. interrogans, but lower than those observed for L. biflexa wildtype. In conclusion, Lig proteins contribute to in vitro control of complement activation on the leptospiral surface, promoting an increased bacterial survival in human serum. PMID:26976804

Big domains are novel Ca²+-binding modules: evidences from big domains of Leptospira immunoglobulin-like (Lig) proteins.

PubMed

Raman, Rajeev; Rajanikanth, V; Palaniappan, Raghavan U M; Lin, Yi-Pin; He, Hongxuan; McDonough, Sean P; Sharma, Yogendra; Chang, Yung-Fu

2010-12-29

Many bacterial surface exposed proteins mediate the host-pathogen interaction more effectively in the presence of Ca²+. Leptospiral immunoglobulin-like (Lig) proteins, LigA and LigB, are surface exposed proteins containing Bacterial immunoglobulin like (Big) domains. The function of proteins which contain Big fold is not known. Based on the possible similarities of immunoglobulin and βγ-crystallin folds, we here explore the important question whether Ca²+ binds to a Big domains, which would provide a novel functional role of the proteins containing Big fold. We selected six individual Big domains for this study (three from the conserved part of LigA and LigB, denoted as Lig A3, Lig A4, and LigBCon5; two from the variable region of LigA, i.e., 9(th) (Lig A9) and 10(th) repeats (Lig A10); and one from the variable region of LigB, i.e., LigBCen2. We have also studied the conserved region covering the three and six repeats (LigBCon1-3 and LigCon). All these proteins bind the calcium-mimic dye Stains-all. All the selected four domains bind Ca²+ with dissociation constants of 2-4 µM. Lig A9 and Lig A10 domains fold well with moderate thermal stability, have β-sheet conformation and form homodimers. Fluorescence spectra of Big domains show a specific doublet (at 317 and 330 nm), probably due to Trp interaction with a Phe residue. Equilibrium unfolding of selected Big domains is similar and follows a two-state model, suggesting the similarity in their fold. We demonstrate that the Lig are Ca²+-binding proteins, with Big domains harbouring the binding motif. We conclude that despite differences in sequence, a Big motif binds Ca²+. This work thus sets up a strong possibility for classifying the proteins containing Big domains as a novel family of Ca²+-binding proteins. Since Big domain is a part of many proteins in bacterial kingdom, we suggest a possible function these proteins via Ca²+ binding.

Big Domains Are Novel Ca2+-Binding Modules: Evidences from Big Domains of Leptospira Immunoglobulin-Like (Lig) Proteins

PubMed Central

Palaniappan, Raghavan U. M.; Lin, Yi-Pin; He, Hongxuan; McDonough, Sean P.; Sharma, Yogendra; Chang, Yung-Fu

2010-01-01

Background Many bacterial surface exposed proteins mediate the host-pathogen interaction more effectively in the presence of Ca2+. Leptospiral immunoglobulin-like (Lig) proteins, LigA and LigB, are surface exposed proteins containing Bacterial immunoglobulin like (Big) domains. The function of proteins which contain Big fold is not known. Based on the possible similarities of immunoglobulin and βγ-crystallin folds, we here explore the important question whether Ca2+ binds to a Big domains, which would provide a novel functional role of the proteins containing Big fold. Principal Findings We selected six individual Big domains for this study (three from the conserved part of LigA and LigB, denoted as Lig A3, Lig A4, and LigBCon5; two from the variable region of LigA, i.e., 9th (Lig A9) and 10th repeats (Lig A10); and one from the variable region of LigB, i.e., LigBCen2. We have also studied the conserved region covering the three and six repeats (LigBCon1-3 and LigCon). All these proteins bind the calcium-mimic dye Stains-all. All the selected four domains bind Ca2+ with dissociation constants of 2–4 µM. Lig A9 and Lig A10 domains fold well with moderate thermal stability, have β-sheet conformation and form homodimers. Fluorescence spectra of Big domains show a specific doublet (at 317 and 330 nm), probably due to Trp interaction with a Phe residue. Equilibrium unfolding of selected Big domains is similar and follows a two-state model, suggesting the similarity in their fold. Conclusions We demonstrate that the Lig are Ca2+-binding proteins, with Big domains harbouring the binding motif. We conclude that despite differences in sequence, a Big motif binds Ca2+. This work thus sets up a strong possibility for classifying the proteins containing Big domains as a novel family of Ca2+-binding proteins. Since Big domain is a part of many proteins in bacterial kingdom, we suggest a possible function these proteins via Ca2+ binding. PMID:21206924

Acquisition of negative complement regulators by the saprophyte Leptospira biflexa expressing LigA or LigB confers enhanced survival in human serum.

PubMed

Castiblanco-Valencia, Mónica M; Fraga, Tatiana R; Breda, Leandro C D; Vasconcellos, Sílvio A; Figueira, Cláudio P; Picardeau, Mathieu; Wunder, Elsio; Ko, Albert I; Barbosa, Angela S; Isaac, Lourdes

2016-05-01

Leptospiral immunoglobulin-like (Lig) proteins are surface exposed molecules present in pathogenic but not in saprophytic Leptospira species. We have previously shown that Lig proteins interact with the soluble complement regulators Factor H (FH), FH like-1 (FHL-1), FH related-1 (FHR-1) and C4b Binding Protein (C4BP). In this study, we used the saprophyte L. biflexa serovar Patoc as a surrogate host to address the specific role of LigA and LigB proteins in leptospiral complement evasion. L. biflexa expressing LigA or LigB was able to acquire FH and C4BP. Bound complement regulators retained their cofactor activities of FI in the proteolytic cleavage of C3b and C4b. Moreover, heterologous expression of ligA and ligB genes in the saprophyte L. biflexa enhanced bacterial survival in human serum. Complement deposition on lig-transformed L. biflexa was assessed by flow cytometry analysis. With regard to MAC deposition, L. biflexa expressing LigA or LigB presented an intermediate profile: MAC deposition levels were greater than those found in the pathogenic L. interrogans, but lower than those observed for L. biflexa wildtype. In conclusion, Lig proteins contribute to in vitro control of complement activation on the leptospiral surface, promoting an increased bacterial survival in human serum. Copyright © 2016 European Federation of Immunological Societies. All rights reserved.

Degradation of lignin β-aryl ether units in Arabidopsis thaliana expressing LigD, LigF and LigG from Sphingomonas paucimobilis SYK-6.

PubMed

Mnich, Ewelina; Vanholme, Ruben; Oyarce, Paula; Liu, Sarah; Lu, Fachuang; Goeminne, Geert; Jørgensen, Bodil; Motawie, Mohammed S; Boerjan, Wout; Ralph, John; Ulvskov, Peter; Møller, Birger L; Bjarnholt, Nanna; Harholt, Jesper

2017-05-01

Lignin is a major polymer in the secondary plant cell wall and composed of hydrophobic interlinked hydroxyphenylpropanoid units. The presence of lignin hampers conversion of plant biomass into biofuels; plants with modified lignin are therefore being investigated for increased digestibility. The bacterium Sphingomonas paucimobilis produces lignin-degrading enzymes including LigD, LigF and LigG involved in cleaving the most abundant lignin interunit linkage, the β-aryl ether bond. In this study, we expressed the LigD, LigF and LigG (LigDFG) genes in Arabidopsis thaliana to introduce postlignification modifications into the lignin structure. The three enzymes were targeted to the secretory pathway. Phenolic metabolite profiling and 2D HSQC NMR of the transgenic lines showed an increase in oxidized guaiacyl and syringyl units without concomitant increase in oxidized β-aryl ether units, showing lignin bond cleavage. Saccharification yield increased significantly in transgenic lines expressing LigDFG, showing the applicability of our approach. Additional new information on substrate specificity of the LigDFG enzymes is also provided. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Heterologous expression of pathogen-specific genes ligA and ligB in the saprophyte Leptospira biflexa confers enhanced adhesion to cultured cells and fibronectin.

PubMed

Figueira, Cláudio Pereira; Croda, Julio; Choy, Henry A; Haake, David A; Reis, Mitermayer G; Ko, Albert I; Picardeau, Mathieu

2011-06-09

In comparison to other bacterial pathogens, our knowledge of the molecular basis of the pathogenesis of leptospirosis is extremely limited. An improved understanding of leptospiral pathogenetic mechanisms requires reliable tools for functional genetic analysis. Leptospiral immunoglobulin-like (Lig) proteins are surface proteins found in pathogenic Leptospira, but not in saprophytes. Here, we describe a system for heterologous expression of the Leptospira interrogans genes ligA and ligB in the saprophyte Leptospira biflexa serovar Patoc. The genes encoding LigA and LigB under the control of a constitutive spirochaetal promoter were inserted into the L. biflexa replicative plasmid. We were able to demonstrate expression and surface localization of LigA and LigB in L. biflexa. We found that the expression of the lig genes significantly enhanced the ability of transformed L. biflexa to adhere in vitro to extracellular matrix components and cultured cells, suggesting the involvement of Lig proteins in cell adhesion. This work reports a complete description of the system we have developed for heterologous expression of pathogen-specific proteins in the saprophytic L. biflexa. We show that expression of LigA and LigB proteins from the pathogen confers a virulence-associated phenotype on L. biflexa, namely adhesion to eukaryotic cells and fibronectin in vitro. This study indicates that L. biflexa can serve as a surrogate host to characterize the role of key virulence factors of the causative agent of leptospirosis.

In vivo sensitivity of the embryonic and adult neural stem cell compartments to low-dose radiation.

PubMed

Barazzuol, Lara; Jeggo, Penny A

2016-08-01

The embryonic brain is radiation-sensitive, with cognitive deficits being observed after exposure to low radiation doses. Exposure of neonates to radiation can cause intracranial carcinogenesis. To gain insight into the basis underlying these outcomes, we examined the response of the embryonic, neonatal and adult brain to low-dose radiation, focusing on the neural stem cell compartments. This review summarizes our recent findings. At E13.5-14.5 the embryonic neocortex encompasses rapidly proliferating stem and progenitor cells. Exploiting mice with a hypomorphic mutation in DNA ligase IV (Lig4(Y288C) ), we found a high level of DNA double-strand breaks (DSBs) at E14.5, which we attribute to the rapid proliferation. We observed endogenous apoptosis in Lig4(Y288C) embryos and in WT embryos following exposure to low radiation doses. An examination of DSB levels and apoptosis in adult neural stem cell compartments, the subventricular zone (SVZ) and the subgranular zone (SGZ) revealed low DSB levels in Lig4(Y288C) mice, comparable with the levels in differentiated neuronal tissues. We conclude that the adult SVZ does not incur high levels of DNA breakage, but sensitively activates apoptosis; apoptosis was less sensitively activated in the SGZ, and differentiated neuronal tissues did not activate apoptosis. P5/P15 mice showed intermediate DSB levels, suggesting that DSBs generated in the embryo can be transmitted to neonates and undergo slow repair. Interestingly, this analysis revealed a stage of high endogenous apoptosis in the neonatal SVZ. Collectively, these studies reveal that the adult neural stem cell compartment, like the embryonic counterpart, can sensitively activate apoptosis. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Heterologous expression of pathogen-specific genes ligA and ligB in the saprophyte Leptospira biflexa confers enhanced adhesion to cultured cells and fibronectin

PubMed Central

2011-01-01

Background In comparison to other bacterial pathogens, our knowledge of the molecular basis of the pathogenesis of leptospirosis is extremely limited. An improved understanding of leptospiral pathogenetic mechanisms requires reliable tools for functional genetic analysis. Leptospiral immunoglobulin-like (Lig) proteins are surface proteins found in pathogenic Leptospira, but not in saprophytes. Here, we describe a system for heterologous expression of the Leptospira interrogans genes ligA and ligB in the saprophyte Leptospira biflexa serovar Patoc. Results The genes encoding LigA and LigB under the control of a constitutive spirochaetal promoter were inserted into the L. biflexa replicative plasmid. We were able to demonstrate expression and surface localization of LigA and LigB in L. biflexa. We found that the expression of the lig genes significantly enhanced the ability of transformed L. biflexa to adhere in vitro to extracellular matrix components and cultured cells, suggesting the involvement of Lig proteins in cell adhesion. Conclusions This work reports a complete description of the system we have developed for heterologous expression of pathogen-specific proteins in the saprophytic L. biflexa. We show that expression of LigA and LigB proteins from the pathogen confers a virulence-associated phenotype on L. biflexa, namely adhesion to eukaryotic cells and fibronectin in vitro. This study indicates that L. biflexa can serve as a surrogate host to characterize the role of key virulence factors of the causative agent of leptospirosis. PMID:21658265

Cloning and Molecular Characterization of an Immunogenic LigA Protein of Leptospira interrogans

PubMed Central

Palaniappan, Raghavan U. M.; Chang, Yung-Fu; Jusuf, S. S. D.; Artiushin, S.; Timoney, John F.; McDonough, Sean P.; Barr, Steve C.; Divers, Thomas J.; Simpson, Kenneth W.; McDonough, Patrick L.; Mohammed, Hussni O.

2002-01-01

A clone expressing a novel immunoreactive leptospiral immunoglobulin-like protein A of 130 kDa (LigA) from Leptospira interrogans serovar pomona type kennewicki was isolated by screening a genomic DNA library with serum from a mare that had recently aborted due to leptospiral infection. LigA is encoded by an open reading frame of 3,675 bp, and the deduced amino acid sequence consists of a series of 90-amino-acid tandem repeats. A search of the NCBI database found that homology of the LigA repeat region was limited to an immunoglobulin-like domain of the bacterial intimin binding protein of Escherichia coli, the cell adhesion domain of Clostridium acetobutylicum, and the invasin of Yersinia pestis. Secondary structure prediction analysis indicates that LigA consists mostly of beta sheets with a few alpha-helical regions. No LigA was detectable by immunoblot analysis of lysates of the leptospires grown in vitro at 30°C or when cultures were shifted to 37°C. Strikingly, immunohistochemistry on kidney from leptospira-infected hamsters demonstrated LigA expression. These findings suggest that LigA is specifically induced only in vivo. Sera from horses, which aborted as a result of natural Leptospira infection, strongly recognize LigA. LigA is the first leptospiral protein described to have 12 tandem repeats and is also the first to be expressed only during infection. Thus, LigA may have value in serodiagnosis or as a protective immunogen in novel vaccines. PMID:12379666

Toward a Last Interglacial Compilation Using a Tephra-based Chronology: a Future Reference For Model-data Comparison

NASA Astrophysics Data System (ADS)

Bazin, L.; Govin, A.; Capron, E.; Nomade, S.; Lemieux-Dudon, B.; Landais, A.

2017-12-01

The Last Interglacial (LIG, 129-116 ka) is a key period to decipher the interactions between the different components of the climate system under warmer-than-preindustrial conditions. Modelling the LIG climate is now part of the CMIP6/PMIP4 targeted simulations. As a result, recent efforts have been made to propose surface temperature compilations focusing on the spatio-temporal evolution of the LIG climate, and not only on its peak warmth as previously proposed. However, the major limitation of these compilations remains in the climatic alignment of records (e.g. temperature, foraminiferal δ18O) that is performed to define the sites' chronologies. Such methods prevent the proper discussion of phase relationship between the different sites. Thanks to recent developments of the Bayesian Datice dating tool, we are now able to build coherent multi-archive chronologies with a proper propagation of the associated uncertainties. We make the best use of common tephra layers identified in well-dated continental archives and marine sediment cores of the Mediterranean region to propose a coherent chronological framework for the LIG independent of any climatic assumption. We then extend this precise chronological context to the North Atlantic as a first step toward a global coherent compilation of surface temperature and stable isotope records. Based on this synthesis, we propose guidelines for the interpretation of different proxies measured from different archives that will be compared with climate model parameters. Finally, we present time-slices (e.g. 127 ka) of the preliminary regional synthesis of temperature reconstructions and stable isotopes to serve as reference for future model-data comparison of the up-coming CMIP6/PMIP4 LIG simulations.

A conserved region of leptospiral immunoglobulin-like A and B proteins as a DNA vaccine elicits a prophylactic immune response against leptospirosis.

PubMed

Forster, Karine M; Hartwig, Daiane D; Seixas, Fabiana K; Bacelo, Kátia L; Amaral, Marta; Hartleben, Cláudia P; Dellagostin, Odir A

2013-05-01

The leptospiral immunoglobulin-like (Lig) proteins LigA and LigB possess immunoglobulin-like domains with 90-amino-acid repeats and are adhesion molecules involved in pathogenicity. They are conserved in pathogenic Leptospira spp. and thus are of interest for use as serodiagnostic antigens and in recombinant vaccine formulations. The N-terminal amino acid sequences of the LigA and LigB proteins are identical, but the C-terminal sequences vary. In this study, we evaluated the protective potential of five truncated forms of LigA and LigB proteins from Leptospira interrogans serovar Canicola as DNA vaccines using the pTARGET mammalian expression vector. Hamsters immunized with the DNA vaccines were subjected to a heterologous challenge with L. interrogans serovar Copenhageni strain Spool via the intraperitoneal route. Immunization with a DNA vaccine encoding LigBrep resulted in the survival of 5/8 (62.5%) hamsters against lethal infection (P < 0.05). None of the control hamsters or animals immunized with the other vaccine preparations survived. The vaccine induced an IgG antibody response and, additionally, conferred sterilizing immunity in 80% of the surviving animals. Our results indicate that the LigBrep DNA vaccine is a promising candidate for inclusion in a protective leptospiral vaccine.

A Conserved Region of Leptospiral Immunoglobulin-Like A and B Proteins as a DNA Vaccine Elicits a Prophylactic Immune Response against Leptospirosis

PubMed Central

Forster, Karine M.; Hartwig, Daiane D.; Seixas, Fabiana K.; Bacelo, Kátia L.; Amaral, Marta; Hartleben, Cláudia P.

2013-01-01

The leptospiral immunoglobulin-like (Lig) proteins LigA and LigB possess immunoglobulin-like domains with 90-amino-acid repeats and are adhesion molecules involved in pathogenicity. They are conserved in pathogenic Leptospira spp. and thus are of interest for use as serodiagnostic antigens and in recombinant vaccine formulations. The N-terminal amino acid sequences of the LigA and LigB proteins are identical, but the C-terminal sequences vary. In this study, we evaluated the protective potential of five truncated forms of LigA and LigB proteins from Leptospira interrogans serovar Canicola as DNA vaccines using the pTARGET mammalian expression vector. Hamsters immunized with the DNA vaccines were subjected to a heterologous challenge with L. interrogans serovar Copenhageni strain Spool via the intraperitoneal route. Immunization with a DNA vaccine encoding LigBrep resulted in the survival of 5/8 (62.5%) hamsters against lethal infection (P < 0.05). None of the control hamsters or animals immunized with the other vaccine preparations survived. The vaccine induced an IgG antibody response and, additionally, conferred sterilizing immunity in 80% of the surviving animals. Our results indicate that the LigBrep DNA vaccine is a promising candidate for inclusion in a protective leptospiral vaccine. PMID:23486420

Leptospira Immunoglobulin-Like Protein B Interacts with the 20th Exon of Human Tropoelastin Contributing to Leptospiral Adhesion to Human Lung Cells

PubMed Central

Hsieh, Ching-Lin; Tseng, Andrew; He, Hongxuan; Kuo, Chih-Jung; Wang, Xuannian; Chang, Yung-Fu

2017-01-01

Leptospira immunoglobulin-like protein B (LigB), a surface adhesin, is capable of mediating the attachment of pathogenic leptospira to the host through interaction with various components of the extracellular matrix (ECM). Human tropoelastin (HTE), the building block of elastin, confers resilience and elasticity to lung, and other tissues. Previously identified Ig-like domains of LigB, including LigB4 and LigB12, bind to HTE, which is likely to promote Leptospira adhesion to lung tissue. However, the molecular mechanism that mediates the LigB-HTE interaction is unclear. In this study, the LigB-binding site on HTE was further pinpointed to a N-terminal region of the 20th exon of HTE (HTE20N). Alanine mutants of basic and aromatic residues on HTE20N significantly reduced binding to the LigB. Additionally, HTE-binding site was narrowed down to the first β-sheet of LigB12. On this binding surface, residues F1054, D1061, A1065, and D1066 were critical for the association with HTE. Most importantly, the recombinant HTE truncates could diminish the binding of LigB to human lung fibroblasts (WI-38) by 68%, and could block the association of LigA-expressing L. biflexa to lung cells by 61%. These findings should expand our understanding of leptospiral pathogenesis, particularly in pulmonary manifestations of leptospirosis. PMID:28536676

Control of Gene Expression in Leptospira spp. by Transcription Activator-Like Effectors Demonstrates a Potential Role for LigA and LigB in Leptospira interrogans Virulence

PubMed Central

Pappas, Christopher J.

2015-01-01

Leptospirosis is a zoonotic disease that affects ∼1 million people annually, with a mortality rate of >10%. Currently, there is an absence of effective genetic manipulation tools for targeted mutagenesis in pathogenic leptospires. Transcription activator-like effectors (TALEs) are a recently described group of repressors that modify transcriptional activity in prokaryotic and eukaryotic cells by directly binding to a targeted sequence within the host genome. To determine the applicability of TALEs within Leptospira spp., two TALE constructs were designed. First, a constitutively expressed TALE gene specific for the lacO-like region upstream of bgaL was trans inserted in the saprophyte Leptospira biflexa (the TALEβgal strain). Reverse transcriptase PCR (RT-PCR) analysis and enzymatic assays demonstrated that BgaL was not expressed in the TALEβgal strain. Second, to study the role of LigA and LigB in pathogenesis, a constitutively expressed TALE gene with specificity for the homologous promoter regions of ligA and ligB was cis inserted into the pathogen Leptospira interrogans (TALElig). LigA and LigB expression was studied by using three independent clones: TALElig1, TALElig2, and TALElig3. Immunoblot analysis of osmotically induced TALElig clones demonstrated 2- to 9-fold reductions in the expression levels of LigA and LigB, with the highest reductions being noted for TALElig1 and TALElig2, which were avirulent in vivo and nonrecoverable from animal tissues. This study reconfirms galactosidase activity in the saprophyte and suggests a role for LigA and LigB in pathogenesis. Collectively, this study demonstrates that TALEs are effective at reducing the expression of targeted genes within saprophytic and pathogenic strains of Leptospira spp., providing an additional genetic manipulation tool for this genus. PMID:26341206

Control of Gene Expression in Leptospira spp. by Transcription Activator-Like Effectors Demonstrates a Potential Role for LigA and LigB in Leptospira interrogans Virulence.

PubMed

Pappas, Christopher J; Picardeau, Mathieu

2015-11-01

Leptospirosis is a zoonotic disease that affects ∼1 million people annually, with a mortality rate of >10%. Currently, there is an absence of effective genetic manipulation tools for targeted mutagenesis in pathogenic leptospires. Transcription activator-like effectors (TALEs) are a recently described group of repressors that modify transcriptional activity in prokaryotic and eukaryotic cells by directly binding to a targeted sequence within the host genome. To determine the applicability of TALEs within Leptospira spp., two TALE constructs were designed. First, a constitutively expressed TALE gene specific for the lacO-like region upstream of bgaL was trans inserted in the saprophyte Leptospira biflexa (the TALEβgal strain). Reverse transcriptase PCR (RT-PCR) analysis and enzymatic assays demonstrated that BgaL was not expressed in the TALEβgal strain. Second, to study the role of LigA and LigB in pathogenesis, a constitutively expressed TALE gene with specificity for the homologous promoter regions of ligA and ligB was cis inserted into the pathogen Leptospira interrogans (TALElig). LigA and LigB expression was studied by using three independent clones: TALElig1, TALElig2, and TALElig3. Immunoblot analysis of osmotically induced TALElig clones demonstrated 2- to 9-fold reductions in the expression levels of LigA and LigB, with the highest reductions being noted for TALElig1 and TALElig2, which were avirulent in vivo and nonrecoverable from animal tissues. This study reconfirms galactosidase activity in the saprophyte and suggests a role for LigA and LigB in pathogenesis. Collectively, this study demonstrates that TALEs are effective at reducing the expression of targeted genes within saprophytic and pathogenic strains of Leptospira spp., providing an additional genetic manipulation tool for this genus. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

The pathways and outcomes of mycobacterial NHEJ depend on the structure of the broken DNA ends

PubMed Central

Aniukwu, Jideofor; Glickman, Michael S.; Shuman, Stewart

2008-01-01

Mycobacteria can repair DNA double-strand breaks (DSBs) via a nonhomologous end-joining (NHEJ) system that includes a dedicated DNA ligase (LigD) and the DNA end-binding protein Ku. Here we exploit an improved plasmid-based NHEJ assay and a collection of Mycobacterium smegmatis strains bearing deletions or mutations in Ku or the DNA ligases to interrogate the contributions of LigD’s three catalytic activities (polymerase, ligase, and 3′ phosphoesterase) and structural domains (POL, LIG, and PE) to the efficiency and molecular outcomes of NHEJ in vivo. By analyzing in parallel the repair of blunt, 5′ overhang, and 3′ overhang DSBs, we discovered a novel end-joining pathway specific to breaks with 3′ overhangs that is Ku- and LigD-independent and perfectly faithful. This 3′ overhang NHEJ pathway is independent of ligases B and C; we surmise that it relies on NAD+-dependent LigA, the essential replicative ligase. We find that efficient repair of blunt and 5′ overhang DSBs depends stringently on Ku and the LigD POL domain, but not on the LigD polymerase activity, which mainly serves to promote NHEJ infidelity. The lack of an effect of PE-inactivating LigD mutations on NHEJ outcomes, especially the balance between deletions and insertions at blunt or 5′ overhang breaks, argues against LigD being the catalyst of deletion formation. Ligase-inactivating LigD mutations (or deletion of the LIG domain) have a modest impact on the efficiency of blunt and 5′ overhang DSB repair, because the strand sealing activity can be provided in trans by one of the other resident ATP-dependent ligases (likely LigC). Reliance on the backup ligase is accompanied by a drastic loss of fidelity during blunt end and 5′ overhang DSB repair. We conclude that the mechanisms of mycobacterial NHEJ are many and the outcomes depend on the initial structures of the DSBs and the available ensemble of end-processing and end-sealing components, which are not limited to Ku and LigD. PMID:18281464

Human DNA ligase III bridges two DNA ends to promote specific intermolecular DNA end joining

PubMed Central

Kukshal, Vandna; Kim, In-Kwon; Hura, Gregory L.; Tomkinson, Alan E.; Tainer, John A.; Ellenberger, Tom

2015-01-01

Mammalian DNA ligase III (LigIII) functions in both nuclear and mitochondrial DNA metabolism. In the nucleus, LigIII has functional redundancy with DNA ligase I whereas LigIII is the only mitochondrial DNA ligase and is essential for the survival of cells dependent upon oxidative respiration. The unique LigIII zinc finger (ZnF) domain is not required for catalytic activity but senses DNA strand breaks and stimulates intermolecular ligation of two DNAs by an unknown mechanism. Consistent with this activity, LigIII acts in an alternative pathway of DNA double strand break repair that buttresses canonical non-homologous end joining (NHEJ) and is manifest in NHEJ-defective cancer cells, but how LigIII acts in joining intermolecular DNA ends versus nick ligation is unclear. To investigate how LigIII efficiently joins two DNAs, we developed a real-time, fluorescence-based assay of DNA bridging suitable for high-throughput screening. On a nicked duplex DNA substrate, the results reveal binding competition between the ZnF and the oligonucleotide/oligosaccharide-binding domain, one of three domains constituting the LigIII catalytic core. In contrast, these domains collaborate and are essential for formation of a DNA-bridging intermediate by adenylated LigIII that positions a pair of blunt-ended duplex DNAs for efficient and specific intermolecular ligation. PMID:26130724

Human DNA ligase III bridges two DNA ends to promote specific intermolecular DNA end joining.

PubMed

Kukshal, Vandna; Kim, In-Kwon; Hura, Gregory L; Tomkinson, Alan E; Tainer, John A; Ellenberger, Tom

2015-08-18

Mammalian DNA ligase III (LigIII) functions in both nuclear and mitochondrial DNA metabolism. In the nucleus, LigIII has functional redundancy with DNA ligase I whereas LigIII is the only mitochondrial DNA ligase and is essential for the survival of cells dependent upon oxidative respiration. The unique LigIII zinc finger (ZnF) domain is not required for catalytic activity but senses DNA strand breaks and stimulates intermolecular ligation of two DNAs by an unknown mechanism. Consistent with this activity, LigIII acts in an alternative pathway of DNA double strand break repair that buttresses canonical non-homologous end joining (NHEJ) and is manifest in NHEJ-defective cancer cells, but how LigIII acts in joining intermolecular DNA ends versus nick ligation is unclear. To investigate how LigIII efficiently joins two DNAs, we developed a real-time, fluorescence-based assay of DNA bridging suitable for high-throughput screening. On a nicked duplex DNA substrate, the results reveal binding competition between the ZnF and the oligonucleotide/oligosaccharide-binding domain, one of three domains constituting the LigIII catalytic core. In contrast, these domains collaborate and are essential for formation of a DNA-bridging intermediate by adenylated LigIII that positions a pair of blunt-ended duplex DNAs for efficient and specific intermolecular ligation. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

The terminal portion of leptospiral immunoglobulin-like protein LigA confers protective immunity against lethal infection in the hamster model of leptospirosis

PubMed Central

Silva, Éverton F.; Medeiros, Marco A.; McBride, Alan J. A.; Matsunaga, Jim; Esteves, Gabriela S.; Ramos, João G. R.; Santos, Cleiton S.; Croda, Júlio; Homma, Akira; Dellagostin, Odir A.; Haake, David A.; Reis, Mitermayer G.; Ko, Albert I.

2007-01-01

Subunit vaccines are a potential intervention strategy against leptospirosis, which is a major public health problem in developing countries and a veterinary disease in livestock and companion animals worldwide. Leptospiral immunoglobulin-like (Lig) proteins are a family of surface-exposed determinants that have Ig-like repeat domains found in virulence factors such as intimin and invasin. We expressed fragments of the repeat domain regions of LigA and LigB from Leptospira interrogans serovar Copenhageni. Immunization of Golden Syrian hamsters with Lig fragments in Freund’s adjuvant induced robust antibody responses against recombinant protein and native protein, as detected by ELISA and immunoblot, respectively. A single fragment, LigANI, which corresponds to the six carboxy-terminal Ig-like repeat domains of the LigA molecule, conferred immunoprotection against mortality (67-100%, P <0.05) in hamsters which received a lethal inoculum of L. interrogans serovar Copenhageni. However, immunization with this fragment did not confer sterilizing immunity. These findings indicate that the carboxy-terminal portion of LigA is an immunoprotective domain and may serve as a vaccine candidate for human and veterinary leptospirosis. PMID:17629368

The terminal portion of leptospiral immunoglobulin-like protein LigA confers protective immunity against lethal infection in the hamster model of leptospirosis.

PubMed

Silva, Everton F; Medeiros, Marco A; McBride, Alan J A; Matsunaga, Jim; Esteves, Gabriela S; Ramos, João G R; Santos, Cleiton S; Croda, Júlio; Homma, Akira; Dellagostin, Odir A; Haake, David A; Reis, Mitermayer G; Ko, Albert I

2007-08-14

Subunit vaccines are a potential intervention strategy against leptospirosis, which is a major public health problem in developing countries and a veterinary disease in livestock and companion animals worldwide. Leptospiral immunoglobulin-like (Lig) proteins are a family of surface-exposed determinants that have Ig-like repeat domains found in virulence factors such as intimin and invasin. We expressed fragments of the repeat domain regions of LigA and LigB from Leptospira interrogans serovar Copenhageni. Immunization of Golden Syrian hamsters with Lig fragments in Freund's adjuvant induced robust antibody responses against recombinant protein and native protein, as detected by ELISA and immunoblot, respectively. A single fragment, LigANI, which corresponds to the six carboxy-terminal Ig-like repeat domains of the LigA molecule, conferred immunoprotection against mortality (67-100%, P<0.05) in hamsters which received a lethal inoculum of L. interrogans serovar Copenhageni. However, immunization with this fragment did not confer sterilizing immunity. These findings indicate that the carboxy-terminal portion of LigA is an immunoprotective domain and may serve as a vaccine candidate for human and veterinary leptospirosis.

Role for cis-acting RNA sequences in the temperature-dependent expression of the multiadhesive lig proteins in Leptospira interrogans.

PubMed

Matsunaga, James; Schlax, Paula J; Haake, David A

2013-11-01

The spirochete Leptospira interrogans causes a systemic infection that provokes a febrile illness. The putative lipoproteins LigA and LigB promote adhesion of Leptospira to host proteins, interfere with coagulation, and capture complement regulators. In this study, we demonstrate that the expression level of the LigA and LigB proteins was substantially higher when L. interrogans proliferated at 37°C instead of the standard culture temperature of 30°C. The RNA comprising the 175-nucleotide 5' untranslated region (UTR) and first six lig codons, whose sequence is identical in ligA and ligB, is predicted to fold into two distinct stem-loop structures separated by a single-stranded region. The ribosome-binding site is partially sequestered in double-stranded RNA within the second structure. Toeprint analysis revealed that in vitro formation of a 30S-tRNA(fMet)-mRNA ternary complex was inhibited unless a 5' deletion mutation disrupted the second stem-loop structure. To determine whether the lig sequence could mediate temperature-regulated gene expression in vivo, the 5' UTR and the first six codons were inserted between the Escherichia coli l-arabinose promoter and bgaB (β-galactosidase from Bacillus stearothermophilus) to create a translational fusion. The lig fragment successfully conferred thermoregulation upon the β-galactosidase reporter in E. coli. The second stem-loop structure was sufficient to confer thermoregulation on the reporter, while sequences further upstream in the 5' UTR slightly diminished expression at each temperature tested. Finally, the expression level of β-galactosidase was significantly higher when point mutations predicted to disrupt base pairs in the second structure were introduced into the stem. Compensatory mutations that maintained base pairing of the stem without restoring the wild-type sequence reinstated the inhibitory effect of the 5' UTR on expression. These results indicate that ligA and ligB expression is limited by double-stranded RNA that occludes the ribosome-binding site. At elevated temperatures, the ribosome-binding site is exposed to promote translation initiation.

Osmotic regulation of expression of two extracellular matrix-binding proteins and a haemolysin of Leptospira interrogans: differential effects on LigA and Sph2 extracellular release.

PubMed

Matsunaga, James; Medeiros, Marco A; Sanchez, Yolanda; Werneid, Kristian F; Ko, Albert I

2007-10-01

The life cycle of the pathogen Leptospira interrogans involves stages outside and inside the host. Entry of L. interrogans from moist environments into the host is likely to be accompanied by the induction of genes encoding virulence determinants and the concomitant repression of genes encoding products required for survival outside of the host. The expression of the adhesin LigA, the haemolysin Sph2 (Lk73.5) and the outer-membrane lipoprotein LipL36 of pathogenic Leptospira species have been reported to be regulated by mammalian host signals. A previous study demonstrated that raising the osmolarity of the leptospiral growth medium to physiological levels encountered in the host by addition of various salts enhanced the levels of cell-associated LigA and LigB and extracellular LigA. In this study, we systematically examined the effects of osmotic upshift with ionic and non-ionic solutes on expression of the known mammalian host-regulated leptospiral genes. The levels of cell-associated LigA, LigB and Sph2 increased at physiological osmolarity, whereas LipL36 levels decreased, corresponding to changes in specific transcript levels. These changes in expression occurred irrespective of whether sodium chloride or sucrose was used as the solute. The increase of cellular LigA, LigB and Sph2 protein levels occurred within hours of adding sodium chloride. Extracellular Sph2 levels increased when either sodium chloride or sucrose was added to achieve physiological osmolarity. In contrast, enhanced levels of extracellular LigA were observed only with an increase in ionic strength. These results indicate that the mechanisms for release of LigA and Sph2 differ during host infection. Thus, osmolarity not only affects leptospiral gene expression by affecting transcript levels of putative virulence determinants but also affects the release of such proteins into the surroundings.

Identification of Three Alcohol Dehydrogenase Genes Involved in the Stereospecific Catabolism of Arylglycerol-β-Aryl Ether by Sphingobium sp. Strain SYK-6▿ †

PubMed Central

Sato, Yusuke; Moriuchi, Hideki; Hishiyama, Shojiro; Otsuka, Yuichiro; Oshima, Kenji; Kasai, Daisuke; Nakamura, Masaya; Ohara, Seiji; Katayama, Yoshihiro; Fukuda, Masao; Masai, Eiji

2009-01-01

Degradation of arylglycerol-β-aryl ether is the most important process in bacterial lignin catabolism. Sphingobium sp. strain SYK-6 degrades guaiacylglycerol-β-guaiacyl ether (GGE) to α-(2-methoxyphenoxy)-β-hydroxypropiovanillone (MPHPV), and then the ether linkage of MPHPV is cleaved to generate α-glutathionyl-β-hydroxypropiovanillone (GS-HPV) and guaiacol. We have characterized three enantioselective glutathione S-transferase genes, including two genes that are involved in the ether cleavage of two enantiomers of MPHPV and one gene that is involved in the elimination of glutathione from a GS-HPV enantiomer. However, the first step in the degradation of four different GGE stereoisomers has not been characterized. In this study, three alcohol dehydrogenase genes, ligL, ligN, and ligO, which conferred GGE transformation activity in Escherichia coli, were isolated from SYK-6 and characterized, in addition to the previously cloned ligD gene. The levels of amino acid sequence identity of the four GGE dehydrogenases, which belong to the short-chain dehydrogenase/reductase family, ranged from 32% to 39%. Each gene was expressed in E. coli, and the stereospecificities of the gene products with the four GGE stereoisomers were determined by using chiral high-performance liquid chromatography with recently synthesized authentic enantiopure GGE stereoisomers. LigD and LigO converted (αR,βS)-GGE and (αR,βR)-GGE into (βS)-MPHPV and (βR)-MPHPV, respectively, while LigL and LigN transformed (αS,βR)-GGE and (αS,βS)-GGE to (βR)-MPHPV and (βS)-MPHPV, respectively. Disruption of the genes indicated that ligD is essential for the degradation of (αR,βS)-GGE and (αR,βR)-GGE and that both ligL and ligN contribute to the degradation of the two other GGE stereoisomers. PMID:19542348

The multifunctional LigB adhesin binds homeostatic proteins with potential roles in cutaneous infection by pathogenic Leptospira interrogans.

PubMed

Choy, Henry A; Kelley, Melissa M; Croda, Julio; Matsunaga, James; Babbitt, Jane T; Ko, Albert I; Picardeau, Mathieu; Haake, David A

2011-02-09

Leptospirosis is a potentially fatal zoonotic disease in humans and animals caused by pathogenic spirochetes, such as Leptospira interrogans. The mode of transmission is commonly limited to the exposure of mucous membrane or damaged skin to water contaminated by leptospires shed in the urine of carriers, such as rats. Infection occurs during seasonal flooding of impoverished tropical urban habitats with large rat populations, but also during recreational activity in open water, suggesting it is very efficient. LigA and LigB are surface localized proteins in pathogenic Leptospira strains with properties that could facilitate the infection of damaged skin. Their expression is rapidly induced by the increase in osmolarity encountered by leptospires upon transition from water to host. In addition, the immunoglobulin-like repeats of the Lig proteins bind proteins that mediate attachment to host tissue, such as fibronectin, fibrinogen, collagens, laminin, and elastin, some of which are important in cutaneous wound healing and repair. Hemostasis is critical in a fresh injury, where fibrinogen from damaged vasculature mediates coagulation. We show that fibrinogen binding by recombinant LigB inhibits fibrin formation, which could aid leptospiral entry into the circulation, dissemination, and further infection by impairing healing. LigB also binds fibroblast fibronectin and type III collagen, two proteins prevalent in wound repair, thus potentially enhancing leptospiral adhesion to skin openings. LigA or LigB expression by transformation of a nonpathogenic saprophyte, L. biflexa, enhances bacterial adhesion to fibrinogen. Our results suggest that by binding homeostatic proteins found in cutaneous wounds, LigB could facilitate leptospirosis transmission. Both fibronectin and fibrinogen binding have been mapped to an overlapping domain in LigB comprising repeats 9-11, with repeat 11 possibly enhancing binding by a conformational effect. Leptospirosis patient antibodies react with the LigB domain, suggesting applications in diagnosis and vaccines that are currently limited by the strain-specific leptospiral lipopolysaccharide coats.

The Multifunctional LigB Adhesin Binds Homeostatic Proteins with Potential Roles in Cutaneous Infection by Pathogenic Leptospira interrogans

PubMed Central

Choy, Henry A.; Kelley, Melissa M.; Croda, Julio; Matsunaga, James; Babbitt, Jane T.; Ko, Albert I.; Picardeau, Mathieu; Haake, David A.

2011-01-01

Leptospirosis is a potentially fatal zoonotic disease in humans and animals caused by pathogenic spirochetes, such as Leptospira interrogans. The mode of transmission is commonly limited to the exposure of mucous membrane or damaged skin to water contaminated by leptospires shed in the urine of carriers, such as rats. Infection occurs during seasonal flooding of impoverished tropical urban habitats with large rat populations, but also during recreational activity in open water, suggesting it is very efficient. LigA and LigB are surface localized proteins in pathogenic Leptospira strains with properties that could facilitate the infection of damaged skin. Their expression is rapidly induced by the increase in osmolarity encountered by leptospires upon transition from water to host. In addition, the immunoglobulin-like repeats of the Lig proteins bind proteins that mediate attachment to host tissue, such as fibronectin, fibrinogen, collagens, laminin, and elastin, some of which are important in cutaneous wound healing and repair. Hemostasis is critical in a fresh injury, where fibrinogen from damaged vasculature mediates coagulation. We show that fibrinogen binding by recombinant LigB inhibits fibrin formation, which could aid leptospiral entry into the circulation, dissemination, and further infection by impairing healing. LigB also binds fibroblast fibronectin and type III collagen, two proteins prevalent in wound repair, thus potentially enhancing leptospiral adhesion to skin openings. LigA or LigB expression by transformation of a nonpathogenic saprophyte, L. biflexa, enhances bacterial adhesion to fibrinogen. Our results suggest that by binding homeostatic proteins found in cutaneous wounds, LigB could facilitate leptospirosis transmission. Both fibronectin and fibrinogen binding have been mapped to an overlapping domain in LigB comprising repeats 9–11, with repeat 11 possibly enhancing binding by a conformational effect. Leptospirosis patient antibodies react with the LigB domain, suggesting applications in diagnosis and vaccines that are currently limited by the strain-specific leptospiral lipopolysaccharide coats. PMID:21347378

Sphingobium sp. SYK-6 LigG involved in lignin degradation is structurally and biochemically related to the glutathione transferase ω class.

PubMed

Meux, Edgar; Prosper, Pascalita; Masai, Eiji; Mulliert, Guillermo; Dumarçay, Stéphane; Morel, Mélanie; Didierjean, Claude; Gelhaye, Eric; Favier, Frédérique

2012-11-16

SpLigG is one of the three glutathione transferases (GSTs) involved in the process of lignin breakdown in the soil bacterium Sphingobium sp. SYK-6. Sequence comparisons showed that SpLigG and several proteobacteria homologues form an independent cluster within cysteine-containing GSTs. The relationship between SpLigG and other GSTs was investigated. The X-ray structure and biochemical properties of SpLigG indicate that this enzyme belongs to the omega class of glutathione transferases. However, the hydrophilic substrate binding site of SpLigG, together with its known ability to stereoselectively deglutathionylate the physiological substrate α-glutathionyl-β-hydroxypropiovanillone, argues for broadening the definition of the omega class. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Structural and functional characterization of the PNKP–XRCC4–LigIV DNA repair complex

DOE PAGES

Aceytuno, R.  Daniel; Piett, Cortt G.; Havali-Shahriari, Zahra; ...

2017-04-27

Non-homologous end joining (NHEJ) repairs DNA double strand breaks in non-cycling eukaryotic cells. NHEJ relies on polynucleotide kinase/phosphatase (PNKP), which generates 5'-phosphate/3'-hydroxyl DNA termini that are critical for ligation by the NHEJ DNA ligase, LigIV. PNKP and LigIV require the NHEJ scaffolding protein, XRCC4. The PNKP FHA domain binds to the CK2-phosphorylated XRCC4 C-terminal tail, while LigIV uses its tandem BRCT repeats to bind the XRCC4 coiled-coil. Yet, the assembled PNKP-XRCC4-LigIV complex remains uncharacterized. Here, we report purification and characterization of a recombinant PNKP-XRCC4-LigIV complex. We show that the stable binding of PNKP in this complex requires XRCC4 phosphorylation andmore » that only one PNKP protomer binds per XRCC4 dimer. Small angle X-ray scattering (SAXS) reveals a flexiblemultistate complex that suggests that both the PNKP FHA and catalytic domains contact the XRCC4 coiled-coil and LigIV BRCT repeats. Hydrogen-deuterium exchange indicates protection of a surface on the PNKP phosphatase domain that may contact XRCC4-LigIV. Amutation on this surface (E326K) causes the hereditary neuro-developmental disorder, MCSZ. This mutation impairs PNKP recruitment to damaged DNA in human cells and provides a possible disease mechanism. Together, this work unveils multipoint contacts between PNKP and XRCC4-LigIV that regulate PNKP recruitment and activity within NHEJ.« less

Structural and functional characterization of the PNKP–XRCC4–LigIV DNA repair complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aceytuno, R.  Daniel; Piett, Cortt G.; Havali-Shahriari, Zahra

Non-homologous end joining (NHEJ) repairs DNA double strand breaks in non-cycling eukaryotic cells. NHEJ relies on polynucleotide kinase/phosphatase (PNKP), which generates 5'-phosphate/3'-hydroxyl DNA termini that are critical for ligation by the NHEJ DNA ligase, LigIV. PNKP and LigIV require the NHEJ scaffolding protein, XRCC4. The PNKP FHA domain binds to the CK2-phosphorylated XRCC4 C-terminal tail, while LigIV uses its tandem BRCT repeats to bind the XRCC4 coiled-coil. Yet, the assembled PNKP-XRCC4-LigIV complex remains uncharacterized. Here, we report purification and characterization of a recombinant PNKP-XRCC4-LigIV complex. We show that the stable binding of PNKP in this complex requires XRCC4 phosphorylation andmore » that only one PNKP protomer binds per XRCC4 dimer. Small angle X-ray scattering (SAXS) reveals a flexiblemultistate complex that suggests that both the PNKP FHA and catalytic domains contact the XRCC4 coiled-coil and LigIV BRCT repeats. Hydrogen-deuterium exchange indicates protection of a surface on the PNKP phosphatase domain that may contact XRCC4-LigIV. Amutation on this surface (E326K) causes the hereditary neuro-developmental disorder, MCSZ. This mutation impairs PNKP recruitment to damaged DNA in human cells and provides a possible disease mechanism. Together, this work unveils multipoint contacts between PNKP and XRCC4-LigIV that regulate PNKP recruitment and activity within NHEJ.« less

Targeted mutagenesis in pathogenic Leptospira species: disruption of the LigB gene does not affect virulence in animal models of leptospirosis.

PubMed

Croda, Julio; Figueira, Claudio Pereira; Wunder, Elsio A; Santos, Cleiton S; Reis, Mitermayer G; Ko, Albert I; Picardeau, Mathieu

2008-12-01

The pathogenic mechanisms of Leptospira interrogans, the causal agent of leptospirosis, remain largely unknown. This is mainly due to the lack of tools for genetically manipulating pathogenic Leptospira species. Thus, homologous recombination between introduced DNA and the corresponding chromosomal locus has never been demonstrated for this pathogen. Leptospiral immunoglobulin-like repeat (Lig) proteins were previously identified as putative Leptospira virulence factors. In this study, a ligB mutant was constructed by allelic exchange in L. interrogans; in this mutant a spectinomycin resistance (Spc(r)) gene replaced a portion of the ligB coding sequence. Gene disruption was confirmed by PCR, immunoblot analysis, and immunofluorescence studies. The ligB mutant did not show decrease virulence compared to the wild-type strain in the hamster model of leptospirosis. In addition, inoculation of rats with the ligB mutant induced persistent colonization of the kidneys. Finally, LigB was not required to mediate bacterial adherence to cultured cells. Taken together, our data provide the first evidence of site-directed homologous recombination in pathogenic Leptospira species. Furthermore, our data suggest that LigB does not play a major role in dissemination of the pathogen in the host and in the development of acute disease manifestations or persistent renal colonization.

Targeted Mutagenesis in Pathogenic Leptospira Species: Disruption of the LigB Gene Does Not Affect Virulence in Animal Models of Leptospirosis▿

PubMed Central

Croda, Julio; Figueira, Claudio Pereira; Wunder, Elsio A.; Santos, Cleiton S.; Reis, Mitermayer G.; Ko, Albert I.; Picardeau, Mathieu

2008-01-01

The pathogenic mechanisms of Leptospira interrogans, the causal agent of leptospirosis, remain largely unknown. This is mainly due to the lack of tools for genetically manipulating pathogenic Leptospira species. Thus, homologous recombination between introduced DNA and the corresponding chromosomal locus has never been demonstrated for this pathogen. Leptospiral immunoglobulin-like repeat (Lig) proteins were previously identified as putative Leptospira virulence factors. In this study, a ligB mutant was constructed by allelic exchange in L. interrogans; in this mutant a spectinomycin resistance (Spcr) gene replaced a portion of the ligB coding sequence. Gene disruption was confirmed by PCR, immunoblot analysis, and immunofluorescence studies. The ligB mutant did not show decrease virulence compared to the wild-type strain in the hamster model of leptospirosis. In addition, inoculation of rats with the ligB mutant induced persistent colonization of the kidneys. Finally, LigB was not required to mediate bacterial adherence to cultured cells. Taken together, our data provide the first evidence of site-directed homologous recombination in pathogenic Leptospira species. Furthermore, our data suggest that LigB does not play a major role in dissemination of the pathogen in the host and in the development of acute disease manifestations or persistent renal colonization. PMID:18809657

LigSearch: a knowledge-based web server to identify likely ligands for a protein target

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beer, Tjaart A. P. de; Laskowski, Roman A.; Duban, Mark-Eugene

LigSearch is a web server for identifying ligands likely to bind to a given protein. Identifying which ligands might bind to a protein before crystallization trials could provide a significant saving in time and resources. LigSearch, a web server aimed at predicting ligands that might bind to and stabilize a given protein, has been developed. Using a protein sequence and/or structure, the system searches against a variety of databases, combining available knowledge, and provides a clustered and ranked output of possible ligands. LigSearch can be accessed at http://www.ebi.ac.uk/thornton-srv/databases/LigSearch.

Redundant function of DNA ligase 1 and 3 in alternative end-joining during immunoglobulin class switch recombination.

PubMed

Masani, Shahnaz; Han, Li; Meek, Katheryn; Yu, Kefei

2016-02-02

Nonhomologous end-joining (NHEJ) is the major DNA double-strand break (DSB) repair pathway in mammals and resolves the DSBs generated during both V(D)J recombination in developing lymphocytes and class switch recombination (CSR) in antigen-stimulated B cells. In contrast to the absolute requirement for NHEJ to resolve DSBs associated with V(D)J recombination, DSBs associated with CSR can be resolved in NHEJ-deficient cells (albeit at a reduced level) by a poorly defined alternative end-joining (A-EJ) pathway. Deletion of DNA ligase IV (Lig4), a core component of the NHEJ pathway, reduces CSR efficiency in a mouse B-cell line capable of robust cytokine-stimulated CSR in cell culture. Here, we report that CSR levels are not further reduced by deletion of either of the two remaining DNA ligases (Lig1 and nuclear Lig3) in Lig4(-/-) cells. We conclude that in the absence of Lig4, Lig1, and Lig3 function in a redundant manner in resolving switch region DSBs during CSR.

A 80-Year Long Coral-Based Temperature Reconstruction for the Last Interglacial from Northern Hispaniola

NASA Astrophysics Data System (ADS)

DeLong, K. L.; Ouellette, G., Jr.; Goodkin, N.; Martin, E. R.; Rosendahl, D. H.; Taylor, F. W.; WU, C. C.; Shen, C. C.

2016-12-01

The Last Interglacial (LIG; 117-128 ka), when sea level was 6 m higher than today, can serve as an analog for future climate scenarios, yet minimal paleoclimatic information exists with seasonal to decadal resolution. The island of Hispaniola is a particularly desirable site for producing sea surface temperature (SST) reconstructions, as it displays significant correlations with SST and precipitation anomalies for much of the tropical and North Atlantic Ocean, and Hispaniola is located in the northern sector of the Atlantic Warm Pool (AWP), a primary moisture source for precipitation in the Americas. Here we present an early LIG (128,626 ±438 (2σ) years) monthly-resolved coral Sr/Ca-SST reconstruction from a well-preserved Siderastrea siderea subfossil coral spanning 80 years from the northern coast of Hispaniola (19.913ºN, 70.925ºW). We compare our LIG SST reconstruction with coral Sr/Ca-SST from three modern coral microatolls of the same species, the longest spanning 80 years, recovered near Port-au Prince, Haiti (18.479070°N, 72.668659°W) after the 2010 Haiti earthquake, as well as a 125 ka LIG model simulation spanning 300 years. We find similar mean SST for the LIG (27.4ºC) and modern corals (27.9ºC) that is consistent with MIS 5e reconstructions in the tropical oceans (27.3-29.6ºC); however, these reconstructions are warmer than the LIG model mean SST for our study site (25.6ºC). Seasonal variability is similar (1.5ºC LIG, 1.0-1.7ºC modern) consistent with the findings of LIG coral reconstructions using the tropical Atlantic coral Diploria strigosa and with climate model simulations suggesting orbital insolation changes driving LIG seasonality. However, our LIG coral contains decadal variability (1.7-3.1ºC) not evident in the shorter LIG coral reconstructions or modern SST records and coral reconstructions yet are present in the LIG model simulation for our study site. This decadal variability may reflect variations in the northern extent of the AWP on decadal time scales, which may vary trade wind strength, westward moisture transport to the Americas, and precipitation in the Atlantic.

Differential effects of Glycyrrhiza species on genotoxic estrogen metabolism: licochalcone A downregulates P450 1B1 whereas isoliquiritigenin stimulates

PubMed Central

Dunlap, Tareisha L.; Wang, Shuai; Simmler, Charlotte; Chen, Shao-Nong; Pauli, Guido F.; Dietz, Birgit M.; Bolton, Judy L.

2015-01-01

Estrogen chemical carcinogenesis involves 4-hydroxylation of estrone/estradiol (E1/E2) by P450 1B1, generating catechol and quinone genotoxic metabolites that cause DNA mutations and initiate/promote breast cancer. Inflammation enhances this effect by up-regulating P450 1B1. The present study tested the three authenticated medicinal species of licorice, [Glycyrrhiza glabra (GG), G. uralensis (GU), and G. inflata (GI)], used by women as dietary supplements, for their anti-inflammatory activities and their ability to modulate estrogen metabolism. The pure compounds, liquiritigenin (LigF), its chalcone isomer isoliquiritigenin (LigC), and the GI specific licochalcone A (LicA) were also tested. The licorice extracts and compounds were evaluated for anti-inflammatory activity by measuring inhibition of iNOS activity in macrophage cells: GI > GG > GU and LigC ≅ LicA > LigF. The Michael acceptor chalcone LicA, is likely responsible for the anti-inflammatory activity of GI. A sensitive LC-MS/MS assay was employed to quantify estrogen metabolism by measuring 2-MeOE1 as non-toxic and 4-MeOE1 as genotoxic biomarkers in the non-tumorigenic human mammary epithelial cell line, MCF-10A. GG, GU, and LigC increased 4-MeOE1, whereas GI and LicA inhibited 2- and 4-MeOE1 levels. GG, GU (5 μg/mL), and LigC (1 μM) also enhanced P450 1B1 expression and activities, which was further increased by inflammatory cytokines (TNF-α and IFN-γ). LicA (1 μM, 10 μM) decreased cytokine- and TCDD-induced, P450 1B1 gene expression and TCDD-induced xenobiotic response element luciferase reporter (IC50=12.3 μM), suggesting an antagonistic effect on the aryl hydrocarbon receptor, which regulates P450 1B1. Similarly, GI (5 μg/mL) reduced cytokine- and TCDD-induced P450 1B1 gene expression. Collectively, these data suggest that of the three licorice species that are used in botanical supplements, GI represents the most promising chemopreventive licorice extract for women’s health. Additionally, the differential effects of the Glycyrrhiza species on estrogen metabolism emphasize the importance of standardization of botanical supplements to species-specific bioactive compounds. PMID:26134484

Processing of DNA double strand breaks by alternative non-homologous end-joining in hyperacetylated chromatin.

PubMed

Manova, Vasilissa; Singh, Satyendra K; Iliakis, George

2012-08-22

Mammalian cells employ at least two subpathways of non-homologous end-joining for the repair of ionizing radiation induced DNA double strand breaks: The canonical DNA-PK-dependent form of non-homologous end-joining (D-NHEJ) and an alternative, slowly operating, error-prone backup pathway (B-NHEJ). In contrast to D-NHEJ, which operates with similar efficiency throughout the cell cycle, B-NHEJ operates more efficiently in G2-phase. Notably, B-NHEJ also shows strong and as of yet unexplained dependency on growth activity and is markedly compromised in serum-deprived cells, or in cells that enter the plateau-phase of growth. The molecular mechanisms underpinning this response remain unknown. Since chromatin structure or changes in chromatin structure are prime candidate-B-NHEJ-modulators, we study here the role of chromatin hyperacetylation, either by HDAC2 knockdown or treatment with the HDAC inhibitor TSA, on the repair by B-NHEJ of IR-induced DSBs. siRNA-mediated knockdown of HDAC2 fails to provoke histone hyperacetylation in Lig4-/- MEFs and has no detectable effect on B-NHEJ function. Treatment with TSA that inhibits multiple HDACs causes efficient, reversible chromatin hyperacetylation in Lig4-/- MEFs, as well as in human HCT116 Lig4-/- cells and the human glioma cell line M059K. The IR yield of DSBs in TSA-treated cells remains similar to that of untreated cells despite the expected chromatin relaxation. In addition, chromatin hyperacetylation leaves unchanged repair of DSBs by B-NHEJ in irradiated exponentially growing, or plateau-phase cells. Notably, under the experimental conditions employed here, chromatin hyperacetylation fails to detectably modulate B-NHEJ in M059K cells as well. In summary, the results show that chromatin acetylation or deacetylation does not affect the kinetics of alternative NHEJ in all types of cells examined both in exponentially growing and serum deprived cultures. We conclude that parameters beyond chromatin acetylation determine B-NHEJ efficiency in the plateau-phase of growth.

Intranasal Pretreatment with Z-Ligustilide, the Main Volatile Component of Rhizoma Chuanxiong, Confers Prophylaxis against Cerebral Ischemia via Nrf2 and HSP70 Signaling Pathways.

PubMed

Li, Juan; Yu, Jie; Ma, Hui; Yang, Na; Li, Li; Zheng, Ding-Ding; Wu, Ming-Xia; Zhao, Zhi-Long; Qi, Hong-Yi

2017-03-01

Z-Ligustilide (Z-LIG) is a major component in Rhizoma Chuanxiong, which has been traditionally used as a health food supplement for the prevention of cerebrovascular disease in China. This study investigates the ability of intranasal Z-LIG pretreatment to enhance protection against neuronal damage in rats with middle cerebral artery occlusion (MCAO) and the role of cellular stress response mechanisms Nrf2 and HSP70. Z-LIG significantly mitigated infarct volume, neurological dysfunction, blood-brain barrier disruption, and brain edema (p < 0.01). Moreover, Z-LIG prevented the loss of collagen IV, occludin, and ZO-1 (p < 0.05) and decreased MMP-2 and -9 levels (p < 0.01). Meanwhile, Z-LIG up-regulated NQO1 and HSP70. Notably, blockage of Nrf2-driven transcription or down-regulation of HSP70 remarkably attenuated the preventive effect of Z-LIG (p < 0.05). Together, intranasal delivery of Z-LIG enhanced protection against ischemic injury via Nrf2 and HSP70 signaling pathways and has prophylactic potential in the population at high risk of stroke.

Cell cycle stage-specific roles of Rad18 in tolerance and repair of oxidative DNA damage

PubMed Central

Yang, Yang; Durando, Michael; Smith-Roe, Stephanie L.; Sproul, Chris; Greenwalt, Alicia M.; Kaufmann, William; Oh, Sehyun; Hendrickson, Eric A.; Vaziri, Cyrus

2013-01-01

The E3 ubiquitin ligase Rad18 mediates tolerance of replication fork-stalling bulky DNA lesions, but whether Rad18 mediates tolerance of bulky DNA lesions acquired outside S-phase is unclear. Using synchronized cultures of primary human cells, we defined cell cycle stage-specific contributions of Rad18 to genome maintenance in response to ultraviolet C (UVC) and H2O2-induced DNA damage. UVC and H2O2 treatments both induced Rad18-mediated proliferating cell nuclear antigen mono-ubiquitination during G0, G1 and S-phase. Rad18 was important for repressing H2O2-induced (but not ultraviolet-induced) double strand break (DSB) accumulation and ATM S1981 phosphorylation only during G1, indicating a specific role for Rad18 in processing of oxidative DNA lesions outside S-phase. However, H2O2-induced DSB formation in Rad18-depleted G1 cells was not associated with increased genotoxin sensitivity, indicating that back-up DSB repair mechanisms compensate for Rad18 deficiency. Indeed, in DNA LigIV-deficient cells Rad18-depletion conferred H2O2-sensitivity, demonstrating functional redundancy between Rad18 and non-homologous end joining for tolerance of oxidative DNA damage acquired during G1. In contrast with G1-synchronized cultures, S-phase cells were H2O2-sensitive following Rad18-depletion. We conclude that although Rad18 pathway activation by oxidative lesions is not restricted to S-phase, Rad18-mediated trans-lesion synthesis by Polη is dispensable for damage-tolerance in G1 (because of back-up non-homologous end joining-mediated DSB repair), yet Rad18 is necessary for damage tolerance during S-phase. PMID:23295675

Plasmin cleaves fibrinogen and the human complement proteins C3b and C5 in the presence of Leptospira interrogans proteins: A new role of LigA and LigB in invasion and complement immune evasion.

PubMed

Castiblanco-Valencia, Mónica Marcela; Fraga, Tatiana Rodrigues; Pagotto, Ana Helena; Serrano, Solange Maria de Toledo; Abreu, Patricia Antonia Estima; Barbosa, Angela Silva; Isaac, Lourdes

2016-05-01

Plasminogen is a single-chain glycoprotein found in human plasma as the inactive precursor of plasmin. When converted to proteolytically active plasmin, plasmin(ogen) regulates both complement and coagulation cascades, thus representing an important target for pathogenic microorganisms. Leptospira interrogans binds plasminogen, which is converted to active plasmin. Leptospiral immunoglobulin-like (Lig) proteins are surface exposed molecules that interact with extracellular matrix components and complement regulators, including proteins of the FH family and C4BP. In this work, we demonstrate that these multifunctional molecules also bind plasminogen through both N- and C-terminal domains. These interactions are dependent on lysine residues and are affected by ionic strength. Competition assays suggest that plasminogen does not share binding sites with C4BP or FH on Lig proteins at physiological molar ratios. Plasminogen bound to Lig proteins is converted to proteolytic active plasmin in the presence of urokinase-type plasminogen activator (uPA). Lig-bound plasmin is able to cleave the physiological substrates fibrinogen and the complement proteins C3b and C5. Taken together, our data point to a new role of LigA and LigB in leptospiral invasion and complement immune evasion. Plasmin(ogen) acquisition by these versatile proteins may contribute to Leptospira infection, favoring bacterial survival and dissemination inside the host. Copyright © 2016. Published by Elsevier GmbH.

7-ketocholesteryl-9-carboxynonanoate enhances ATP binding cassette transporter A1 expression mediated by PPARγ in THP-1 macrophages.

PubMed

Chi, Yan; Wang, Le; Liu, Yuanyuan; Ma, Yanhua; Wang, Renjun; Han, Xiaofei; Qiao, Hui; Lin, Jiabin; Matsuura, Eiji; Liu, Shuqian; Liu, Qingping

2014-06-01

ATP binding cassette transporter A1 (ABCA1) is a member of the ATP-binding cassette transporter family. It plays an essential role in mediating the efflux of excess cholesterol. It is known that peroxisome proliferator-activated receptor gamma (PPARγ) promoted ABCA1 expression. We previously found 7-ketocholesteryl-9-carboxynonanoate (oxLig-1) upregulated ABCA1 partially through CD36 mediated signals. In the present study, we intended to test if PPARγ signally is involved in the upregulation mediated by oxLig-1. First, we docked oxLig-1 and the ligand-binding domain (LBD) of PPARγ by using AutoDock 3.05 and subsequently confirmed the binding by ELISA assay. Western blotting analyses showed that oxLig-1 induces liver X receptor alpha (LXRα), PPARγ and consequently ABCA1 expression. Furthermore, oxLig-1 significantly enhanced ApoA-I-mediated cholesterol efflux. Pretreatment with an inhibitor for PPARγ (GW9662) or/and LXRα (GGPP) attenuated oxLig-1-induced ABCA1 expression. Under PPARγ knockdown by using PPARγ-shRNA, oxLig-1-induced ABCA1 expression and cholesterol efflux in THP-1 macrophages was blocked by 62% and 25% respectively. These observations suggest that oxLig-1 is a novel PPARγ agonist, promoting ApoA-I-mediated cholesterol efflux from THP-1 macrophages by increasing ABCA1 expression via induction of PPARγ. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Induction of NAD(P)H:quinone oxidoreductase 1 (NQO1) by Glycyrrhiza species used for women's health: differential effects of the Michael acceptors isoliquiritigenin and licochalcone A

PubMed Central

Hajirahimkhan, Atieh; Simmler, Charlotte; Dong, Huali; Lantvit, Daniel D.; Li, Guannan; Chen, Shao-Nong; Nikolić, Dejan; Pauli, Guido F.; van Breemen, Richard B.; Dietz, Birgit M.; Bolton, Judy L.

2016-01-01

For the alleviation of menopausal symptoms, women frequently turn to botanical dietary supplements, such as licorice and hops. In addition to estrogenic properties, these botanicals could also have chemopreventive effects. We have previously shown that hops and its Michael acceptor xanthohumol (XH) induced the chemoprevention enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1), in vitro and in vivo. Licorice species could also induce NQO1, as they contain the Michael acceptors isoliquiritigenin (LigC) found in Glycyrrhiza glabra (GG), G. uralensis (GU), and G. inflata (GI) and licochalcone A (LicA) which is only found in GI. These licorice species and hops induced NQO1 activity in murine hepatoma (Hepa1c1c7) cells; hops >> GI > GG ≅ GU. Similar to the known chemopreventive compounds curcumin (turmeric), sulforaphane (broccoli), and XH, LigC and LicA were active dose-dependently; sulforaphane >> XH > LigC > LicA ≅ curcumin >> LigF. Induction of the antioxidant response element-luciferase in human hepatoma (Hep-G2-ARE-C8) cells suggested involvement of the Keap1-Nrf2 pathway. GG, GU, and LigC also induced NQO1 in non-tumorigenic breast epithelial MCF-10A cells. In female Sprague-Dawley rats treated with GG and GU, LigC and LigF were detected in the liver and mammary gland. GG weakly enhanced NQO1 activity in the mammary tissue but not in the liver. Treatment with LigC alone did not induce NQO1 in vivo most likely due to its conversion to LigF, extensive metabolism, and its low bioavailability in vivo. These data show the chemopreventive potential of licorice species in vitro could be due to LigC and LicA and emphasize the importance of chemical and biological standardization of botanicals used as dietary supplements. Although the in vivo effects in the rat model after four day treatment are minimal, it must be emphasized that menopausal women take these supplements for extended periods of time and long-term beneficial effects are quite possible. PMID:26473469

75 FR 37786 - Crosstex LIG, LLC; Notice of Baseline Filing

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-30

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR10-40-000] Crosstex LIG, LLC; Notice of Baseline Filing June 23, 2010. Take notice that on June 21, 2010, Crosstex LIG, LLC submitted a baseline filing of its FERC Operating Statement for services provided under Section 311 of the...

Z-ligustilide ameliorated ultraviolet B-induced oxidative stress and inflammatory cytokine production in human keratinocytes through upregulation of Nrf2/HO-1 and suppression of NF-κB pathway.

PubMed

Wu, Zhouwei; Uchi, Hiroshi; Morino-Koga, Saori; Shi, Weimin; Furue, Masutaka

2015-09-01

Ultraviolet B (UVB), a harmful environmental factor, is responsible for a variety of skin disorders including skin inflammation through reactive oxygen species (ROS) and inflammatory mediator production. Here, we investigated the effect of Z-ligustilide (Z-lig), an active ingredient isolated from the medicinal plants Cnidium officinale and Angelica acutiloba, on UVB-induced ROS generation and inflammatory mediator production in normal human epidermal keratinocytes (NHEKs) as well as its underlying mechanisms. Z-lig significantly rescued UVB-induced NHEKs damage in a dosage-dependent manner. Pretreatment of NHEKs with Z-lig inhibited UVB-induced ROS production in NHEKs. Both silencing the nuclear factor E2-related factor 2 (Nrf2) and the supplement of tin protoporphyrin IX (SnPP), a haeme oxygenase-1 (HO-1) inhibitor, cancelled the inhibitory effect of Z-lig on UVB-induced ROS upregulation in NHEKs. Moreover, pretreatment of NHEKs with Z-lig reduced UVB-induced nuclear factor kappa B (NF-κB)-dependent inflammatory mediators (IL-6, IL-8 and MCP-1) production at both mRNA and protein level. In the presence of Z-lig, UVB-induced NF-κB subunit p65 nuclear translocation was abolished, and the IκBα degradation was suppressed. Taken together, these findings suggest that Z-lig can suppress UVB-induced ROS generation through Nrf2/HO-1 upregulation and inflammation by suppressing the NF-κB pathway, suggesting that Z-lig may be beneficial in protecting skin from UVB exposure. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sulfur-Doped Laser-Induced Porous Graphene Derived from Polysulfone-Class Polymers and Membranes.

PubMed

Singh, Swatantra P; Li, Yilun; Zhang, Jibo; Tour, James M; Arnusch, Christopher J

2018-01-23

Graphene based materials have profoundly impacted research in nanotechnology, and this has significantly advanced biomedical, electronics, energy, and environmental applications. Laser-induced graphene (LIG) is made photothermally and has enabled a rapid route for graphene layers on polyimide surfaces. However, polysulfone (PSU), poly(ether sulfone) (PES), and polyphenylsulfone (PPSU) are highly used in numerous applications including medical, energy, and water treatment and they are critical components of polymer membranes. Here we show LIG fabrication on PSU, PES, and PPSU resulting in conformal sulfur-doped porous graphene embedded in polymer dense films or porous substrates using reagent- and solvent-free methods in a single step. We demonstrate the applicability as flexible electrodes with enhanced electrocatalytic hydrogen peroxide generation, as antifouling surfaces and as antimicrobial hybrid membrane-LIG porous filters. The properties and surface morphology of the conductive PSU-, PES-, and PPSU-LIG could be modulated using variable laser duty cycles. The LIG electrodes showed enhanced hydrogen peroxide generation compared to LIG made on polyimide, and showed exceptional biofilm resistance and potent antimicrobial killing effects when treated with Pseudomonas aeruginosa and mixed bacterial culture. The hybrid PES-LIG membrane-electrode ensured complete elimination of bacterial viability in the permeate (6 log reduction), in a flow-through filtration mode at a water flux of ∼500 L m -2 h -1 (2.5 V) and at ∼22 000 L m -2 h -1 (20 V). Due to the widespread use of PSU, PES, and PPSU in modern society, these functional PSU-, PES-, and PPSU-LIG surfaces have great potential to be incorporated into biomedical, electronic, energy and environmental devices and technologies.

Glacial terminations and the Last Interglacial in the Okhotsk Sea; Their implication to global climatic changes

NASA Astrophysics Data System (ADS)

Gorbarenko, Sergey; Velivetskaya, Tatyana; Malakhov, Mikhail; Bosin, Aleksandr

2017-05-01

Paleoclimate data from the Okhotsk Sea (OS) over Terminations II and I (TII, TI), and the Last and Present Interglacial (LIG, PIG) periods were compiled in order to examine Northern Hemisphere climate and sea level changes. Based on records of four AMS 14C-dated OS cores over TI-PIG, it is argued that the OS productivity/climate, IRD (ice-rafted debris), and benthic foraminiferal oxygen isotope (δ18Obf) proxies provide representative and in-phase evidence of the Northern Hemisphere climate and continental ice sheet changes consistent with the LR 04 δ18Obf curve. Chronologies for two central OS cores over TII-LIG-cooling event 23 (C23) were constructed by correlating OS productivity proxies with well-dated δ18O records of Chinese speleothems because OS environment is modulated by East Asian Monsoon; and, as well as correlating measured magnetic paleointensity excursions with those in the dated PISO-1500 paleointensity stack. Results show several OS climatic and environment states, including TII coeval with Asian Weak Monsoon Interval (WMI) II since 136 ka, LIG with a sharp two-step transition (130.2-129 ka) and demise at С25 (116.5 ka), and last glaciation with coolings at C24 (111 ka) and C23. The OS productivity and IRD records demonstrate certain climate amelioration in the middle of WMI-II, and two insignificant cooling events inside the LIG marked by C27 (126 ka) and C26 (120.6 ka). OS δ18Obf records of both cores demonstrate a gradual trend of lighter values since around 131.5 ka BP, continuing from the onset of LIG (129 ka) to minimum values at 126 ka BP (C27), then nearly constant values until 121.5 ka, followed by a slight increase up to 120.6 ka (C26), and a subsequent strong increase up to 116.5 ka (C25). The magnitude of OS δ18Obf oscillations is 1.35‰, which is less than those in the N. Atlantic. It may therefore be suggested that this OS index probably tracks changes in continental ice sheet volume and sea level.

First Insights of the Eemian Hydroclimate of the Snowy Mountains, Australia.

NASA Astrophysics Data System (ADS)

Campbell, M.; Wong, H.; McGrath, G. S.; McGowan, H. A.; Callow, J. N.

2016-12-01

Geologic archives from the Last Interglacial (LIG) provide an opportunity to investigate the likely impacts of a future warmer climate on the hydroclimate of regions sensitive to climate change. Here we present early results from the analysis of a stalagmite from the Yarrangobilly Caves complex in Kosciuszko National Park, Australia - a marginal alpine setting believed to be highly susceptible to the impacts of global warming. Five uranium-series dates show that this stalagmite grew continuously from 123.77 - 117.74 ka B.P. Trace element analysis (Mg/Ca and Sr/Ca) shows that Mg/Ca and Sr/Ca correlate at lags of 40 to 100 years during the period 122.21 ka - 120.37 ka (MIS 5e). Wavelet power spectra show significant periodicity at 60 years in both the Sr/Ca and Mg/Ca record during this time. During the period 120.2 ka - 119.8 ka the Sr/Ca record continues to display significant periodicity at 60 years, while similar periodicity at this scale in the Mg/Ca record is limited to 119.7 ka - 119.6 ka. While it has been suggested that Mg/Ca and Sr/Ca must covary and be in phase in order to interpret `wet' vs `dry' proxies (Tremaine & Froelich 2013), others have shown that Mg/Ca and Sr/Ca can move in and out of phase, attributed to wind-blown inputs of Sr (Frumkin & Stein 2004; Li et al. 2005; Cross et al. 2015). It has been suggested that, due to this and other factors that make Sr less likely to be concentrated during prior calcite precipitation, Mg/Ca may be a better indicator of infiltration rates (Steponaitis et al. 2015). The disconnect between Mg/Ca and Sr/Ca in our record suggests that they had different climatic forcings in south-east Australia during the LIG, and the breakdown in the relationship coincides with peak Mg/Ca in the record and peak SST in the Western Pacific (Lea 2004). Periodicity of 60 years is common in the global climate system and is thought to be astronomical in origin. This periodicity is similar also to the penta-decadal (50-70 yr) cycle of the Pacific Decadal Oscillation. Results indicate that this signal dominated the south-eastern Australian climate signal recorded by the stalagmite during the lead up to the height of the LIG. This signal may therefore be significant under a warmer climate as a dominant cycle in the hydroclimate of the Australian Alpine region.

Genotoxin induced mutagenesis in the model plant Physcomitrella patens.

PubMed

Holá, Marcela; Kozák, Jaroslav; Vágnerová, Radka; Angelis, Karel J

2013-01-01

The moss Physcomitrella patens is unique for the high frequency of homologous recombination, haploid state, and filamentous growth during early stages of the vegetative growth, which makes it an excellent model plant to study DNA damage responses. We used single cell gel electrophoresis (comet) assay to determine kinetics of response to Bleomycin induced DNA oxidative damage and single and double strand breaks in wild type and mutant lig4 Physcomitrella lines. Moreover, APT gene when inactivated by induced mutations was used as selectable marker to ascertain mutational background at nucleotide level by sequencing of the APT locus. We show that extensive repair of DSBs occurs also in the absence of the functional LIG4, whereas repair of SSBs is seriously compromised. From analysis of induced mutations we conclude that their accumulation rather than remaining lesions in DNA and blocking progression through cell cycle is incompatible with normal plant growth and development and leads to sensitive phenotype.

Genotoxin Induced Mutagenesis in the Model Plant Physcomitrella patens

PubMed Central

Holá, Marcela; Kozák, Jaroslav; Vágnerová, Radka; Angelis, Karel J.

2013-01-01

The moss Physcomitrella patens is unique for the high frequency of homologous recombination, haploid state, and filamentous growth during early stages of the vegetative growth, which makes it an excellent model plant to study DNA damage responses. We used single cell gel electrophoresis (comet) assay to determine kinetics of response to Bleomycin induced DNA oxidative damage and single and double strand breaks in wild type and mutant lig4 Physcomitrella lines. Moreover, APT gene when inactivated by induced mutations was used as selectable marker to ascertain mutational background at nucleotide level by sequencing of the APT locus. We show that extensive repair of DSBs occurs also in the absence of the functional LIG4, whereas repair of SSBs is seriously compromised. From analysis of induced mutations we conclude that their accumulation rather than remaining lesions in DNA and blocking progression through cell cycle is incompatible with normal plant growth and development and leads to sensitive phenotype. PMID:24383055

Processing of DNA double strand breaks by alternative non-homologous end-joining in hyperacetylated chromatin

PubMed Central

2012-01-01

Background Mammalian cells employ at least two subpathways of non-homologous end-joining for the repair of ionizing radiation induced DNA double strand breaks: The canonical DNA-PK-dependent form of non-homologous end-joining (D-NHEJ) and an alternative, slowly operating, error-prone backup pathway (B-NHEJ). In contrast to D-NHEJ, which operates with similar efficiency throughout the cell cycle, B-NHEJ operates more efficiently in G2-phase. Notably, B-NHEJ also shows strong and as of yet unexplained dependency on growth activity and is markedly compromised in serum-deprived cells, or in cells that enter the plateau-phase of growth. The molecular mechanisms underpinning this response remain unknown. Since chromatin structure or changes in chromatin structure are prime candidate-B-NHEJ-modulators, we study here the role of chromatin hyperacetylation, either by HDAC2 knockdown or treatment with the HDAC inhibitor TSA, on the repair by B-NHEJ of IR-induced DSBs. Results siRNA-mediated knockdown of HDAC2 fails to provoke histone hyperacetylation in Lig4-/- MEFs and has no detectable effect on B-NHEJ function. Treatment with TSA that inhibits multiple HDACs causes efficient, reversible chromatin hyperacetylation in Lig4-/- MEFs, as well as in human HCT116 Lig4-/- cells and the human glioma cell line M059K. The IR yield of DSBs in TSA-treated cells remains similar to that of untreated cells despite the expected chromatin relaxation. In addition, chromatin hyperacetylation leaves unchanged repair of DSBs by B-NHEJ in irradiated exponentially growing, or plateau-phase cells. Notably, under the experimental conditions employed here, chromatin hyperacetylation fails to detectably modulate B-NHEJ in M059K cells as well. Conclusions In summary, the results show that chromatin acetylation or deacetylation does not affect the kinetics of alternative NHEJ in all types of cells examined both in exponentially growing and serum deprived cultures. We conclude that parameters beyond chromatin acetylation determine B-NHEJ efficiency in the plateau-phase of growth. PMID:22908892

Differential regulation and impact of fucosyltransferase VII and core 2 β1,6-N-acetyl-glycosaminyltransferase for generation of E-selectin and P-selectin ligands in murine CD4+ T cells

PubMed Central

Schroeter, Micha F; Ratsch, Boris A; Lehmann, Jeanette; Baumgrass, Ria; Hamann, Alf; Syrbe, Uta

2012-01-01

Ligands for E-selectin and P-selectin (E-lig and P-lig) are induced on CD4+ T cells upon differentiation into effector T cells. Glycosyltransferases, especially α 1,3-fucosyltransferase VII (FucT-VII) and core 2 β1,6-N-acetyl-glycosaminyltransferase I (C2GlcNAcT-I), are critical for their synthesis. We here analysed the signals that control the expression of E-lig, P-lig and mRNA coding for FucT-VII and C2GlcNAcT-I. In line with previous reports, we found that P-lig expression correlates with the regulation of C2GlcNAcT-I, whereas E-lig expression can occur at low levels of C2GlcNAcT-I mRNA but requires high FucT-VII mRNA expression. Interestingly, the two enzymes are regulated by different signals. Activation-induced C2GlcNAcT-I up-regulation under permissive (T helper type 1) conditions was strongly reduced by cyclosporin A (CsA), suggesting the involvement of T-cell receptor-dependent, calcineurin/NFAT-dependent signals in combination with interleukin-12 (IL-12) -mediated signals in the regulation of C2GlcNAcT-I. In contrast, expression of FucT-VII mRNA was not significantly inhibited by CsA. Interleukin-4 inhibited the expression of FucT-VII but IL-2 and IL-7 were found to support induction of FucT-VII and E-lig. E-selectin, P-selectin and their ligands initially appeared to have rather overlapping functions. These findings however, unravel striking differences in the regulation of E-lig and P-lig expression, dictated by the dominance of FucT-VII and C2GlcNAcT-I, respectively, and their dependency on signals from either promiscuous or homeostatic cytokines (FucT-VII) or a strong T-cell receptor signal in combination with inflammatory cytokines in case of C2GlcNAcT-I. PMID:23039181

LigParGen web server: an automatic OPLS-AA parameter generator for organic ligands

PubMed Central

Dodda, Leela S.

2017-01-01

Abstract The accurate calculation of protein/nucleic acid–ligand interactions or condensed phase properties by force field-based methods require a precise description of the energetics of intermolecular interactions. Despite the progress made in force fields, small molecule parameterization remains an open problem due to the magnitude of the chemical space; the most critical issue is the estimation of a balanced set of atomic charges with the ability to reproduce experimental properties. The LigParGen web server provides an intuitive interface for generating OPLS-AA/1.14*CM1A(-LBCC) force field parameters for organic ligands, in the formats of commonly used molecular dynamics and Monte Carlo simulation packages. This server has high value for researchers interested in studying any phenomena based on intermolecular interactions with ligands via molecular mechanics simulations. It is free and open to all at jorgensenresearch.com/ligpargen, and has no login requirements. PMID:28444340

Solution structure of leptospiral LigA4 Big domain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mei, Song; Zhang, Jiahai; Zhang, Xuecheng

Pathogenic Leptospiraspecies express immunoglobulin-like proteins which serve as adhesins to bind to the extracellular matrices of host cells. Leptospiral immunoglobulin-like protein A (LigA), a surface exposed protein containing tandem repeats of bacterial immunoglobulin-like (Big) domains, has been proved to be involved in the interaction of pathogenic Leptospira with mammalian host. In this study, the solution structure of the fourth Big domain of LigA (LigA4 Big domain) from Leptospira interrogans was solved by nuclear magnetic resonance (NMR). The structure of LigA4 Big domain displays a similar bacterial immunoglobulin-like fold compared with other Big domains, implying some common structural aspects of Bigmore » domain family. On the other hand, it displays some structural characteristics significantly different from classic Ig-like domain. Furthermore, Stains-all assay and NMR chemical shift perturbation revealed the Ca{sup 2+} binding property of LigA4 Big domain. - Highlights: • Determining the solution structure of a bacterial immunoglobulin-like domain from a surface protein of Leptospira. • The solution structure shows some structural characteristics significantly different from the classic Ig-like domains. • A potential Ca{sup 2+}-binding site was identified by strains-all and NMR chemical shift perturbation.« less

Structure-guided Mutational Analysis of the Nucleotidyltransferase Domain of Escherichia coli DNA Ligase (LigA).

PubMed

Wang, Li Kai; Zhu, Hui; Shuman, Stewart

2009-03-27

NAD(+)-dependent DNA ligases (LigA) are ubiquitous in bacteria, where they are essential for growth and present attractive targets for antimicrobial drug discovery. LigA has a distinctive modular structure in which a nucleotidyltransferase catalytic domain is flanked by an upstream NMN-binding module and by downstream OB-fold, zinc finger, helix-hairpin-helix, and BRCT domains. Here we conducted a structure-function analysis of the nucleotidyltransferase domain of Escherichia coli LigA, guided by the crystal structure of the LigA-DNA-adenylate intermediate. We tested the effects of 29 alanine and conservative mutations at 15 amino acids on ligase activity in vitro and in vivo. We thereby identified essential functional groups that coordinate the reactive phosphates (Arg(136)), contact the AMP adenine (Lys(290)), engage the phosphodiester backbone flanking the nick (Arg(218), Arg(308), Arg(97) plus Arg(101)), or stabilize the active domain fold (Arg(171)). Finer analysis of the mutational effects revealed step-specific functions for Arg(136), which is essential for the reaction of LigA with NAD(+) to form the covalent ligase-AMP intermediate (step 1) and for the transfer of AMP to the nick 5'-PO(4) to form the DNA-adenylate intermediate (step 2) but is dispensable for phosphodiester formation at a preadenylylated nick (step 3).

Characterization of Mycobacterium smegmatis PolD2 and PolD1 as RNA/DNA polymerases homologous to the POL domain of bacterial DNA ligase D

PubMed Central

Zhu, Hui; Bhattarai, Hitesh; Yan, Han-Guang; Shuman, Stewart; Glickman, Michael S.

2013-01-01

Mycobacteria exploit nonhomologous end-joining (NHEJ) to repair DNA double-strand breaks. The core NHEJ machinery comprises the homodimeric DNA end-binding protein Ku and DNA ligase D (LigD), a modular enzyme composed of a C-terminal ATP-dependent ligase domain (LIG), a central 3’-phosphoesterase domain (PE), and an N-terminal polymerase domain (POL). LigD POL is proficient at adding templated and nontemplated deoxynucleotide and ribonucleotides to DNA ends in vitro and is the catalyst in vivo of unfaithful NHEJ events involving nontemplated single-nucleotide additions to blunt DSB ends. Here, we identify two mycobacterial proteins, PolD1 and PolD2, as stand-alone homologs of the LigD POL domain. Biochemical characterization of PolD1 and PolD2 shows that they resemble LigD POL in their monomeric quaternary structures, their ability to add templated and nontemplated nucleotides to primer-templates and blunt ends, and their preference for rNTPs versus dNTPs. Deletion of polD1, polD2, or both, in an M. smegmatis strain carrying an inactivating mutation in LigD POL failed to reveal a role for PolD1 or PolD2 in templated nucleotide additions during NHEJ of 5’-overhang DSBs or in clastogen resistance. Whereas our results document the existence and characteristics of new stand-alone members of the LigD POL family of RNA/DNA polymerases, they imply that other polymerases can perform fill-in synthesis during mycobacterial NHEJ. PMID:23198659

Structural and biological evaluation of lignin addition to simple and silver-doped hydroxyapatite thin films synthesized by matrix-assisted pulsed laser evaporation.

PubMed

Janković, A; Eraković, S; Ristoscu, C; Mihailescu Serban, N; Duta, L; Visan, A; Stan, G E; Popa, A C; Husanu, M A; Luculescu, C R; Srdić, V V; Janaćković, Dj; Mišković-Stanković, V; Bleotu, C; Chifiriuc, M C; Mihailescu, I N

2015-01-01

We report on thin film deposition by matrix-assisted pulsed laser evaporation of simple hydroxyapatite (HA) or silver (Ag) doped HA combined with the natural biopolymer organosolv lignin (Lig) (Ag:HA-Lig). Solid cryogenic target of aqueous dispersions of Ag:HA-Lig composite and its counterpart without silver (HA-Lig) were prepared for evaporation using a KrF* excimer laser source. The expulsed material was assembled onto TiO2/Ti substrata or silicon wafers and subjected to physical-chemical investigations. Smooth, uniform films adherent to substratum were observed. The chemical analyses confirmed the presence of the HA components, but also evidenced traces of Ag and Lig. Deposited HA was Ca deficient, which is indicative of a film with increased solubility. Recorded X-ray Diffraction patterns were characteristic for amorphous films. Lig presence in thin films was undoubtedly proved by both X-ray Photoelectron and Fourier Transform Infra-Red Spectroscopy analyses. The microbiological evaluation showed that the newly assembled surfaces exhibited an inhibitory activity both on the initial steps of biofilm forming, and on mature bacterial and fungal biofilm development. The intensity of the anti-biofilm activity was positively influenced by the presence of the Lig and/or Ag, in the case of Staphylococcus aureus, Pseudomonas aeruginosa and Candida famata biofilms. The obtained surfaces exhibited a low cytotoxicity toward human mesenchymal stem cells, being therefore promising candidates for fabricating implantable biomaterials with increased biocompatibility and resistance to microbial colonization and further biofilm development.

Last interglacial temperature seasonality reconstructed from tropical Atlantic corals

NASA Astrophysics Data System (ADS)

Brocas, William M.; Felis, Thomas; Obert, J. Christina; Gierz, Paul; Lohmann, Gerrit; Scholz, Denis; Kölling, Martin; Scheffers, Sander R.

2016-09-01

Reconstructions of last interglacial (LIG, MIS 5e, ∼127-117 ka) climate offer insights into the natural response and variability of the climate system during a period partially analogous to future climate change scenarios. We present well preserved fossil corals (Diploria strigosa) recovered from the southern Caribbean island of Bonaire (Caribbean Netherlands). These have been precisely dated by the 230Th/U-method to between 130 and 120 ka ago. Annual banding of the coral skeleton enabled construction of time windows of monthly resolved strontium/calcium (Sr/Ca) temperature proxy records. In conjunction with a previously published 118 ka coral record, our eight records of up to 37 years in length, cover a total of 105 years within the LIG period. From these, sea surface temperature (SST) seasonality and variability in the tropical North Atlantic Ocean is reconstructed. We detect similar to modern SST seasonality of ∼2.9 °C during the early (130 ka) and the late LIG (120-118 ka). However, within the mid-LIG, a significantly higher than modern SST seasonality of 4.9 °C (at 126 ka) and 4.1 °C (at 124 ka) is observed. These findings are supported by climate model simulations and are consistent with the evolving amplitude of orbitally induced changes in seasonality of insolation throughout the LIG, irrespective of wider climatic instabilities that characterised this period. The climate model simulations suggest that the SST seasonality changes documented in our LIG coral Sr/Ca records are representative of larger regions within the tropical North Atlantic. These simulations also suggest that the reconstructed SST seasonality increase during the mid-LIG is caused primarily by summer warming. A 124 ka old coral documents, for the first time, evidence of decadal SST variability in the tropical North Atlantic during the LIG, akin to that observed in modern instrumental records.

Characterizing the Promiscuity of LigAB, a Lignin Catabolite Degrading Extradiol Dioxygenase from Sphingomonas paucimobilis SYK-6

PubMed Central

Barry, Kevin P.; Taylor, Erika A.

2014-01-01

LigAB from Sphingomonas paucimobilis SYK-6 is the only structurally characterized dioxygenase of the largely uncharacterized superfamily of Type II extradiol dioxygenases (EDO). This enzyme catalyzes the oxidative ring-opening of protocatechuate (3,4-dihydroxybenzoic acid or PCA) in a pathway allowing the degradation of lignin derived aromatic compounds (LDACs). LigAB has also been shown to utilize two other LDACs from the same metabolic pathway as substrates, gallate, and 3-O-methyl gallate; however, kcat/KM had not been reported for any of these compounds. In order to assess the catalytic efficiency and get insights into the observed promiscuity of this enzyme, steady-state kinetic analyses were performed for LigAB with these and a library of related compounds. The dioxygenation of PCA by LigAB was highly efficient, with a kcat of 51 s−1 and a kcat/KM of 4.26 × 106 M−1s−1. LigAB demonstrated the ability to use a variety of catecholic molecules as substrates beyond the previously identified gallate and 3-O-methyl gallate, including 3,4-dihydroxybenzamide, homoprotocatechuate, catechol, and 3,4-dihydroxybenzonitrile. Interestingly, 3,4-dihydroxybenzamide (DHBAm) behaves in a manner similar to that of the preferred benzoic acid substrates, with a kcat/Km value only ~4-fold lower than that for gallate and ~10-fold higher than that for 3-O-methyl gallate. All of these most active substrates demonstrate mechanistic inactivation of LigAB. Additionally, DHBAm exhibits potent product inhibition that leads to an inactive enzyme, being more highly deactivating at lower substrate concentration, a phenomena that, to our knowledge, has not been reported for another dioxygenase substrate/product pair. These results provide valuable catalytic insight into the reactions catalyzed by LigAB and make it the first Type II EDO that is fully characterized both structurally and kinetically. PMID:23977959

Reduced Perinatal Leptin Availability May Contribute to Adverse Metabolic Programming in a Rat Model of Uteroplacental Insufficiency.

PubMed

Nüsken, Eva; Wohlfarth, Maria; Lippach, Gregor; Rauh, Manfred; Schneider, Holm; Dötsch, Jörg; Nüsken, Kai-Dietrich

2016-05-01

Leptin availability in perinatal life critically affects metabolic programming. We tested the hypothesis that uteroplacental insufficiency and intrauterine stress affect perinatal leptin availability in rat offspring. Pregnant rats underwent bilateral uterine vessel ligation (LIG; n = 14), sham operation (SOP; n = 12), or no operation (controls, n = 14). Fetal livers (n = 180), placentas (n = 180), and maternal blood were obtained 4 hours (gestational day [E] 19), 24 hours (E20), and 72 hours (E22) after surgery. In the offspring, we took blood samples on E22 (n = 44), postnatal day (P) 1 (n = 29), P2 (n = 16), P7 (n = 30), and P12 (n = 30). Circulating leptin (ELISA) was significantly reduced in LIG (E22, P1, P2) and SOP offspring (E22). Postnatal leptin surge was delayed in LIG but was accelerated in SOP offspring. Placental leptin gene expression (quantitative RT-PCR) was reduced in LIG (E19, E20, E22) and SOP (E20, E22). Hepatic leptin receptor (Lepr-a, mediating leptin degradation) gene expression was increased in LIG fetuses (E20, E22) only. Surprisingly, hypoxia-inducible factors (Hif; Western blot) were unaltered in placentas and were reduced in the livers of LIG (Hif1a, E20; Hif2a, E19, E22) and SOP (Hif2a, E19) fetuses. Gene expression of prolyl hydroxylase 3, a factor expressed under hypoxic conditions contributing to Hif degradation, was increased in livers of LIG (E19, E20, E22) and SOP (E19) fetuses and in placentas of LIG and SOP (E19). In summary, reduced placental leptin production, increased fetal leptin degradation, and persistent perinatal hypoleptinemia are present in intrauterine growth restriction offspring, especially after uteroplacental insufficiency, and may contribute to perinatal programming of leptin resistance and adiposity in later life.

Towards a new paleotemperature proxy from reef coral occurrences.

PubMed

Lauchstedt, Andreas; Pandolfi, John M; Kiessling, Wolfgang

2017-09-05

Global mean temperature is thought to have exceeded that of today during the last interglacial episode (LIG, ~ 125,000 yrs b.p.) but robust paleoclimate data are still rare in low latitudes. Occurrence data of tropical reef corals may provide new proxies of low latitude sea-surface temperatures. Using modern reef coral distributions we developed a geographically explicit model of sea surface temperatures. Applying this model to coral occurrence data of the LIG provides a latitudinal U-shaped pattern of temperature anomalies with cooler than modern temperatures around the equator and warmer subtropical climes. Our results agree with previously published estimates of LIG temperatures and suggest a poleward broadening of the habitable zone for reef corals during the LIG.

Last stop on the road to repair: structure of E. coli DNA ligase bound to nicked DNA-adenylate.

PubMed

Nandakumar, Jayakrishnan; Nair, Pravin A; Shuman, Stewart

2007-04-27

NAD(+)-dependent DNA ligases (LigA) are ubiquitous in bacteria and essential for growth. Their distinctive substrate specificity and domain organization vis-a-vis human ATP-dependent ligases make them outstanding targets for anti-infective drug discovery. We report here the 2.3 A crystal structure of Escherichia coli LigA bound to an adenylylated nick, which captures LigA in a state poised for strand closure and reveals the basis for nick recognition. LigA envelopes the DNA within a protein clamp. Large protein domain movements and remodeling of the active site orchestrate progression through the three chemical steps of the ligation reaction. The structure inspires a strategy for inhibitor design.

Leptospira Immunoglobulin-Like Protein B (LigB) Binds to Both the C-Terminal 23 Amino Acids of Fibrinogen αC Domain and Factor XIII: Insight into the Mechanism of LigB-Mediated Blockage of Fibrinogen α Chain Cross-Linking.

PubMed

Hsieh, Ching-Lin; Chang, Eric; Tseng, Andrew; Ptak, Christopher; Wu, Li-Chen; Su, Chun-Li; McDonough, Sean P; Lin, Yi-Pin; Chang, Yung-Fu

2016-09-01

The coagulation system provides a primitive but effective defense against hemorrhage. Soluble fibrinogen (Fg) monomers, composed of α, β and γ chains, are recruited to provide structural support for the formation of a hemostatic plug. Fg binds to platelets and is processed into a cross-linked fibrin polymer by the enzymatic clotting factors, thrombin and Factor XIII (FXIII). The newly formed fibrin-platelet clot can act as barrier to protect against pathogens from entering the bloodstream. Further, injuries caused by bacterial infections can be confined to the initial wound site. Many pathogenic bacteria have Fg-binding adhesins that can circumvent the coagulation pathway and allow the bacteria to sidestep containment. Fg expression is upregulated during lung infection providing an attachment surface for bacteria with the ability to produce Fg-binding adhesins. Fg binding by leptospira might play a crucial factor in Leptospira-associated pulmonary hemorrhage, the main factor contributing to lethality in severe cases of leptospirosis. The 12th domain of Leptospira immunoglobulin-like protein B (LigB12), a leptospiral adhesin, interacts with the C-terminus of FgαC (FgαCC). In this study, the binding site for LigB12 was mapped to the final 23 amino acids at the C-terminal end of FgαCC (FgαCC8). The association of FgαCC8 with LigB12 (ELISA, KD = 0.76 μM; SPR, KD = 0.96 μM) was reduced by mutations of both charged residues (R608, R611 and H614 from FgαCC8; D1061 from LigB12) and hydrophobic residues (I613 from FgαCC8; F1054 and A1065 from LigB12). Additionally, LigB12 bound strongly to FXIII and also inhibited fibrin formation, suggesting that LigB can disrupt coagulation by suppressing FXIII activity. Here, the detailed binding mechanism of a leptospiral adhesin to a host hemostatic factor is characterized for the first time and should provide better insight into the pathogenesis of leptospirosis.

Leptospira Immunoglobulin-Like Protein B (LigB) Binds to Both the C-Terminal 23 Amino Acids of Fibrinogen αC Domain and Factor XIII: Insight into the Mechanism of LigB-Mediated Blockage of Fibrinogen α Chain Cross-Linking

PubMed Central

Hsieh, Ching-Lin; Chang, Eric; Tseng, Andrew; Ptak, Christopher; Wu, Li-Chen; Su, Chun-Li; McDonough, Sean P.; Lin, Yi-Pin; Chang, Yung-Fu

2016-01-01

The coagulation system provides a primitive but effective defense against hemorrhage. Soluble fibrinogen (Fg) monomers, composed of α, β and γ chains, are recruited to provide structural support for the formation of a hemostatic plug. Fg binds to platelets and is processed into a cross-linked fibrin polymer by the enzymatic clotting factors, thrombin and Factor XIII (FXIII). The newly formed fibrin-platelet clot can act as barrier to protect against pathogens from entering the bloodstream. Further, injuries caused by bacterial infections can be confined to the initial wound site. Many pathogenic bacteria have Fg-binding adhesins that can circumvent the coagulation pathway and allow the bacteria to sidestep containment. Fg expression is upregulated during lung infection providing an attachment surface for bacteria with the ability to produce Fg-binding adhesins. Fg binding by leptospira might play a crucial factor in Leptospira-associated pulmonary hemorrhage, the main factor contributing to lethality in severe cases of leptospirosis. The 12th domain of Leptospira immunoglobulin-like protein B (LigB12), a leptospiral adhesin, interacts with the C-terminus of FgαC (FgαCC). In this study, the binding site for LigB12 was mapped to the final 23 amino acids at the C-terminal end of FgαCC (FgαCC8). The association of FgαCC8 with LigB12 (ELISA, KD = 0.76 μM; SPR, KD = 0.96 μM) was reduced by mutations of both charged residues (R608, R611 and H614 from FgαCC8; D1061 from LigB12) and hydrophobic residues (I613 from FgαCC8; F1054 and A1065 from LigB12). Additionally, LigB12 bound strongly to FXIII and also inhibited fibrin formation, suggesting that LigB can disrupt coagulation by suppressing FXIII activity. Here, the detailed binding mechanism of a leptospiral adhesin to a host hemostatic factor is characterized for the first time and should provide better insight into the pathogenesis of leptospirosis. PMID:27622634

Mechanistic Assessment of DNA Ligase as an Antibacterial Target in Staphylococcus aureus

PubMed Central

Podos, Steven D.; Thanassi, Jane A.

2012-01-01

We report the use of a known pyridochromanone inhibitor with antibacterial activity to assess the validity of NAD+-dependent DNA ligase (LigA) as an antibacterial target in Staphylococcus aureus. Potent inhibition of purified LigA was demonstrated in a DNA ligation assay (inhibition constant [Ki] = 4.0 nM) and in a DNA-independent enzyme adenylation assay using full-length LigA (50% inhibitory concentration [IC50] = 28 nM) or its isolated adenylation domain (IC50 = 36 nM). Antistaphylococcal activity was confirmed against methicillin-susceptible and -resistant S. aureus (MSSA and MRSA) strains (MIC = 1.0 μg/ml). Analysis of spontaneous resistance potential revealed a high frequency of emergence (4 × 10−7) of high-level resistant mutants (MIC > 64) with associated ligA lesions. There were no observable effects on growth rate in these mutants. Of 22 sequenced clones, 3 encoded point substitutions within the catalytic adenylation domain and 19 in the downstream oligonucleotide-binding (OB) fold and helix-hairpin-helix (HhH) domains. In vitro characterization of the enzymatic properties of four selected mutants revealed distinct signatures underlying their resistance to inhibition. The infrequent adenylation domain mutations altered the kinetics of adenylation and probably elicited resistance directly. In contrast, the highly represented OB fold domain mutations demonstrated a generalized resistance mechanism in which covalent LigA activation proceeds normally and yet the parameters of downstream ligation steps are altered. A resulting decrease in substrate Km and a consequent increase in substrate occupancy render LigA resistant to competitive inhibition. We conclude that the observed tolerance of staphylococcal cells to such hypomorphic mutations probably invalidates LigA as a viable target for antistaphylococcal chemotherapy. PMID:22585221

Uteroplacental insufficiency after bilateral uterine artery ligation in the rat: impact on postnatal glucose and lipid metabolism and evidence for metabolic programming of the offspring by sham operation.

PubMed

Nüsken, Kai-Dietrich; Dötsch, Jörg; Rauh, Manfred; Rascher, Wolfgang; Schneider, Holm

2008-03-01

Ligation of the uterine arteries (LIG) in rats serves as a model of intrauterine growth restriction and subsequent developmental programming of impaired glucose tolerance, hyperinsulinemia, and adiposity in the offspring. Its impact on lipid metabolism has been less well investigated. We compared parameters of glucose and lipid metabolism and glucocorticoid levels in the offspring of dams that underwent either LIG or sham operation (SOP) with those of untreated controls. Blood parameters including insulin, leptin, and visfatin as well as body weight, food intake, and creatinine clearance were recorded up to an age of 30 wk. Glucose tolerance tests were performed, and both leptin and visfatin expression in liver, muscle, and epididymal and mesenteric fat was quantified by RT-PCR. After catch-up growth, weight gain of all groups was similar, despite lower food intake of the LIG rats. LIG offspring showed impaired glucose tolerance from the age of 15 wk as well as elevated glycosylated hemoglobin and corticosterone levels. However, the body fat content of both LIG and SOP animals increased relative to controls, and both showed elevated triglyceride, total cholesterol, and leptin levels as well as a reduced proportion of high-density lipoprotein cholesterol. Thus, use of the LIG model requires both SOP and untreated controls. Although only LIG is associated with impaired glucose tolerance, pathogenic programming of the lipid metabolism can also be induced by SOP. Visfatin does not appear to be involved in the disturbed glucose metabolism after intrauterine growth restriction and may represent only a marker of fat accumulation.

Traditional Chinese Medicine Curcumin Sensitizes Human Colon Cancer to Radiation by Altering the Expression of DNA Repair-related Genes.

PubMed

Yang, Guangen; Qiu, Jianming; Wang, Dong; Tao, Yong; Song, Yihuan; Wang, Hongtao; Tang, Juping; Wang, Xing; Sun, Y U; Yang, Zhijian; Hoffman, Robert M

2018-01-01

The aim of the present study was to investigate the radio-sensitizing efficacy of curcumin, a traditional Chinese medicine (TCM) on colon cancer cells in vitro and in vivo. Human colon cancer HT-29 cells were treated with curcumin (2.5 μM), irradiation (10 Gy) and the combination of irradiation and curcumin. Cell proliferation was assessed using the MTT assay. Apoptotic cells were detected by Annexin V-PE/7-AAD analysis. PCR was performed to determine differential-expression profiling of 95 DNA-repair genes in irradiated cells and cells treated with both irradiation and curcumin. Differentially-expressed genes were confirmed by Western blotting. In vivo radio-sensitizing efficacy of curcumin was assessed in a xenograft mouse model of HT-29 colon cancer. Curcumin was administrated daily by intraperitoneal injection at 20 mg/kg/dose. Mice received irradiation (10 Gy) twice weekly. Apoptosis of the cancer cells following treatment was determined by TUNEL staining. Irradiation induced proliferation inhibition and apoptosis of HT-29 cells in vitro. Concurrent curcumin treatment sensitized the HT-29 tumor to irradiation (p<0.01). DNA repair-related genes CCNH and XRCC5 were upregulated and LIG4 and PNKP downregulated by the combination of curcumin and irradiation compared with irradiation alone (p<0.05). Combined treatment of curcumin and irradiation resulted in a significantly greater tumor-growth inhibition and apoptosis compared to irradiation treatment alone (p<0.01). Curcumin sensitizes human colon cancer in vitro and in vivo to radiation. Downregulation of LIG4 and PNKP and upregulation of XRCC5 and CCNH DNA-repair-related genes were involved in the radio-sensitizing efficacy of curcumin in colon cancer. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Multiferroic homochiral metal-organic framework.

PubMed

Ye, Qiong; Fu, Da-Wei; Tian, Hang; Xiong, Ren-Gen; Chan, Philip Wai Hong; Huang, Songping D

2008-02-04

The hydrothermal reaction of (L)-ethyl lactate (Lig-Et) with Tb(ClO(4))(3).6H(2)O gives colorless block (Lig)(2)Tb(H(2)O)(2)(ClO(4)) (1), in which 1 displays a laminar 2D framework. Ferroelectric and magnetic property measurements reveal that 1 probably is the first example of two "ferroic" metal-organic frameworks. Ferroelectricity of its analogue, (Lig)(2)Tb(D(2)O)(2)(ClO(4)) (2), further confirms the presence of the ferroelectric deuterium effect.

Structure-guided mutational analysis of the nucleotidyltransferase domain of Escherichia coli NAD+-dependent DNA ligase (LigA).

PubMed

Zhu, Hui; Shuman, Stewart

2005-04-01

NAD+-dependent DNA ligase (LigA) is essential for bacterial growth and a potential target for antimicrobial drug discovery. Here we queried the role of 14 conserved amino acids of Escherichia coli LigA by alanine scanning and thereby identified five new residues within the nucleotidyltransferase domain as being essential for LigA function in vitro and in vivo. Structure activity relationships were determined by conservative mutagenesis for the Glu-173, Arg-200, Arg-208, and Arg-277 side chains, as well as four other essential side chains that had been identified previously (Lys-115, Asp-117, Asp-285, and Lys-314). In addition, we identified Lys-290 as important for LigA activity. Reference to the structure of Enterococcus faecalis LigA allowed us to discriminate three classes of essential/important side chains that: (i) contact NAD+ directly (Lys-115, Glu-173, Lys-290, and Lys-314); (ii) comprise the interface between the NMN-binding domain (domain Ia) and the nucleotidyltransferase domain or comprise part of a nick-binding site on the surface of the nucleotidyltransferase domain (Arg-200 and Arg-208); or (iii) stabilize the active site fold of the nucleotidyltransferase domain (Arg-277). Analysis of mutational effects on the isolated ligase adenylylation and phosphodiester formation reactions revealed different functions for essential side chains at different steps of the DNA ligase pathway, consistent with the proposal that the active site is serially remodeled as the reaction proceeds.

Sensitivity of the ViroSeq HIV-1 Genotyping System for Detection of the K103N Resistance Mutation in HIV-1 Subtypes A, C, and D

PubMed Central

Church, Jessica D.; Jones, Dana; Flys, Tamara; Hoover, Donald; Marlowe, Natalia; Chen, Shu; Shi, Chanjuan; Eshleman, James R.; Guay, Laura A.; Jackson, J. Brooks; Kumwenda, Newton; Taha, Taha E.; Eshleman, Susan H.

2006-01-01

The US Food and Drug Administration-cleared ViroSeq HIV-1 Genotyping System (ViroSeq) and other population sequencing-based human immunodeficiency virus type 1 (HIV-1) genotyping methods detect antiretroviral drug resistance mutations present in the major viral population of a test sample. These assays also detect some mutations in viral variants that are present as mixtures. We compared detection of the K103N nevirapine resistance mutation using ViroSeq and a sensitive, quantitative point mutation assay, LigAmp. The LigAmp assay measured the percentage of K103N-containing variants in the viral population (percentage of K103N). We analyzed 305 samples with HIV-1 subtypes A, C, and D collected from African women after nevirapine administration. ViroSeq detected K103N in 100% of samples with >20% K103N, 77.8% of samples with 10 to 20% K103N, 71.4% of samples with 5 to 10% K103N, and 16.9% of samples with 1 to 5% K103N. The sensitivity of ViroSeq for detection of K103N was similar for subtypes A, C, and D. These data indicate that the ViroSeq system reliably detects the K103N mutation at levels above 20% and frequently detects the mutation at lower levels. Further studies are needed to compare the sensitivity of different assays for detection of HIV-1 drug resistance mutations and to determine the clinical relevance of HIV-1 minority variants. PMID:16931582

Optoelectrofluidic field separation based on light-intensity gradients

PubMed Central

Lee, Sanghyun; Park, Hyun Jin; Yoon, Jin Sung; Kang, Kwan Hyoung

2010-01-01

Optoelectrofluidic field separation (OEFS) of particles under light -intensity gradient (LIG) is reported, where the LIG illumination on the photoconductive layer converts the short-ranged dielectrophoresis (DEP) force to the long-ranged one. The long-ranged DEP force can compete with the hydrodynamic force by alternating current electro-osmosis (ACEO) over the entire illumination area for realizing effective field separation of particles. In the OEFS system, the codirectional illumination and observation induce the levitation effect, compensating the attenuation of the DEP force under LIG illumination by slightly floating particles from the surface. Results of the field separation and concentration of diverse particle pairs (0.82–16 μm) are well demonstrated, and conditions determining the critical radius and effective particle manipulation are discussed. The OEFS with codirectional LIG strategy could be a promising particle manipulation method in many applications where a rapid manipulation of biological cells and particles over the entire working area are of interest. PMID:20697461

Optoelectrofluidic field separation based on light-intensity gradients.

PubMed

Lee, Sanghyun; Park, Hyun Jin; Yoon, Jin Sung; Kang, Kwan Hyoung

2010-07-14

Optoelectrofluidic field separation (OEFS) of particles under light -intensity gradient (LIG) is reported, where the LIG illumination on the photoconductive layer converts the short-ranged dielectrophoresis (DEP) force to the long-ranged one. The long-ranged DEP force can compete with the hydrodynamic force by alternating current electro-osmosis (ACEO) over the entire illumination area for realizing effective field separation of particles. In the OEFS system, the codirectional illumination and observation induce the levitation effect, compensating the attenuation of the DEP force under LIG illumination by slightly floating particles from the surface. Results of the field separation and concentration of diverse particle pairs (0.82-16 mum) are well demonstrated, and conditions determining the critical radius and effective particle manipulation are discussed. The OEFS with codirectional LIG strategy could be a promising particle manipulation method in many applications where a rapid manipulation of biological cells and particles over the entire working area are of interest.

Inhibiting Mitochondrial DNA Ligase IIIα Activates Caspase 1-Dependent Apoptosis in Cancer Cells.

PubMed

Sallmyr, Annahita; Matsumoto, Yoshihiro; Roginskaya, Vera; Van Houten, Bennett; Tomkinson, Alan E

2016-09-15

Elevated levels of DNA ligase IIIα (LigIIIα) have been identified as a biomarker of an alteration in DNA repair in cancer cells that confers hypersensitivity to a LigIIIα inhibitor, L67, in combination with a poly (ADP-ribose) polymerase inhibitor. Because LigIIIα functions in the nucleus and mitochondria, we examined the effect of L67 on these organelles. Here, we show that, although the DNA ligase inhibitor selectively targets mitochondria, cancer and nonmalignant cells respond differently to disruption of mitochondrial DNA metabolism. Inhibition of mitochondrial LigIIIα in cancer cells resulted in abnormal mitochondrial morphology, reduced levels of mitochondrial DNA, and increased levels of mitochondrially generated reactive oxygen species that caused nuclear DNA damage. In contrast, these effects did not occur in nonmalignant cells. Furthermore, inhibition of mitochondrial LigIIIα activated a caspase 1-dependent apoptotic pathway, which is known to be part of inflammatory responses induced by pathogenic microorganisms in cancer, but not nonmalignant cells. These results demonstrate that the disruption of mitochondrial DNA metabolism elicits different responses in nonmalignant and cancer cells and suggests that the abnormal response in cancer cells may be exploited in the development of novel therapeutic strategies that selectively target cancer cells. Cancer Res; 76(18); 5431-41. ©2016 AACR. ©2016 American Association for Cancer Research.

Structure of aryl O -demethylase offers molecular insight into a catalytic tyrosine-dependent mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kohler, Amanda C.; Mills, Matthew J. L.; Adams, Paul D.

Some strains of soil and marine bacteria have evolved intricate metabolic pathways for using environmentally derived aromatics as a carbon source. Many of these metabolic pathways go through intermediates such as vanillate, 3-O-methylgallate, and syringate. Demethylation of these compounds is essential for downstream aryl modification, ring opening, and subsequent assimilation of these compounds into the tricarboxylic acid (TCA) cycle, and, correspondingly, there are a variety of associated aryl demethylase systems that vary in complexity. Intriguingly, only a basic understanding of the least complex system, the tetrahydrofolate-dependent aryl demethylase LigM from Sphingomonas paucimobilis, a bacterial strain that metabolizes lignin-derived aromatics, wasmore » previously available. LigM-catalyzed demethylation enables further modification and rin g opening of the single-ring aromatics vanillate and 3-Omethylgallate, which are common byproducts of biofuel production. We characterize aryl O-demethylation by LigM and report its 1.81-Å crystal structure, revealing a unique demethylase fold and a canonical folate-binding domain. Structural homology and geometry optimization calculations enabled the identification of LigM's tetrahydrofolate-binding site and protein-folate interactions. Computationally guided mutagenesis and kinetic analyses allowed the identification of the enzyme's aryl-binding site location and determination of its unique, catalytic tyrosine-dependent reaction mechanism. This work defines LigM as a distinct demethylase, both structurally and functionally, and provides insight into demethylation and its reaction requirements. Our results afford the mechanistic details required for efficient utilization of LigM as a tool for aryl O-demethylation and as a component of synthetic biology efforts to valorize previously underused aromatic compounds.« less

Convergence of prevalence rates of diabetes and cardiometabolic risk factors in middle and low income groups in urban India: 10-year follow-up of the Chennai Urban Population Study.

PubMed

Deepa, Mohan; Anjana, Ranjit Mohan; Manjula, Datta; Narayan, K M Venkat; Mohan, Viswanathan

2011-07-01

The aim of this study was to look for temporal changes in the prevalence of diabetes and cardiometabolic risk factors in two residential colonies in Chennai. Chennai Urban Population Study (CUPS) was carried out between 1996-1998 in Chennai in two residential colonies representing the middle income group (MIG) and lower income group (LIG), respectively. The MIG had twice the prevalence rate of diabetes as the LIG and higher prevalence rates of hypertension, obesity, and dyslipidemia. They were motivated to increase their physical activity, which led to the building of a park. The LIG was given standard lifestyle advice. Follow-up surveys of both colonies were performed after a period of 10 years. In the MIG, the prevalence of diabetes increased from 12.4 to 15.4% (24% increase), while in the LIG, it increased from 6.5 to 15.3% (135% increase, p < .001). In the LIG, the prevalence rates of central obesity (baseline vs follow-up, male: 30.8 vs 50.9%, p < .001; female: 16.9 vs 49.8%, p < .001), hypertension (8.4 vs 20.1%, p < .001), hypercholesterolemia (14.2 vs. 20.4%, p < .05), and hypertriglyceridemia (8.0 vs 23.5%, p < .001) significantly increased and became similar to that seen in the MIG. There is a rapid reversal of socioeconomic gradient for diabetes and cardiometabolic risk factors in urban India with a convergence of prevalence rates among people in the MIG and LIG. This could have a serious economic impact on poor people in developing countries such as India. © 2011 Diabetes Technology Society.

Structure of aryl O -demethylase offers molecular insight into a catalytic tyrosine-dependent mechanism

DOE PAGES

Kohler, Amanda C.; Mills, Matthew J. L.; Adams, Paul D.; ...

2017-04-03

Some strains of soil and marine bacteria have evolved intricate metabolic pathways for using environmentally derived aromatics as a carbon source. Many of these metabolic pathways go through intermediates such as vanillate, 3-O-methylgallate, and syringate. Demethylation of these compounds is essential for downstream aryl modification, ring opening, and subsequent assimilation of these compounds into the tricarboxylic acid (TCA) cycle, and, correspondingly, there are a variety of associated aryl demethylase systems that vary in complexity. Intriguingly, only a basic understanding of the least complex system, the tetrahydrofolate-dependent aryl demethylase LigM from Sphingomonas paucimobilis, a bacterial strain that metabolizes lignin-derived aromatics, wasmore » previously available. LigM-catalyzed demethylation enables further modification and rin g opening of the single-ring aromatics vanillate and 3-Omethylgallate, which are common byproducts of biofuel production. We characterize aryl O-demethylation by LigM and report its 1.81-Å crystal structure, revealing a unique demethylase fold and a canonical folate-binding domain. Structural homology and geometry optimization calculations enabled the identification of LigM's tetrahydrofolate-binding site and protein-folate interactions. Computationally guided mutagenesis and kinetic analyses allowed the identification of the enzyme's aryl-binding site location and determination of its unique, catalytic tyrosine-dependent reaction mechanism. This work defines LigM as a distinct demethylase, both structurally and functionally, and provides insight into demethylation and its reaction requirements. Our results afford the mechanistic details required for efficient utilization of LigM as a tool for aryl O-demethylation and as a component of synthetic biology efforts to valorize previously underused aromatic compounds.« less

Moderate volume of high relative training intensity produces greater strength gains compared with low and high volumes in competitive weightlifters.

PubMed

González-Badillo, Juan José; Izquierdo, Mikel; Gorostiaga, Esteban M

2006-02-01

The purpose of this study was to examine the effect of 3 volumes of heavy resistance, average relative training intensity (expressed as a percentage of 1 repetition maximum that represented the absolute kilograms lifted divided by the number of repetitions performed) programs on maximal strength (1RM) in Snatch (Sn), Clean & Jerk (C&J), and Squat (Sq). Twenty-nine experienced (>3 years), trained junior weightlifters were randomly assigned into 1 of 3 groups: low-intensity group (LIG; n = 12), moderate-intensity group (MIG; n = 9), and high-intensity group (HIG; n = 8). All subjects trained for 10 weeks, 4-5 days a week, in a periodized routine using the same exercises and training volume (expressed as total number of repetitions performed at intensities equal to or greater than 60% of 1RM), but different programmed total repetitions at intensities of >90-100% of 1RM for the entire 10-week period: LIG (46 repetitions), MIG (93 repetitions), and HIG (184 repetitions). During the training period, MIG and LIG showed a significant increase (p < 0.01-0.05) for C&J (10.5% and 3% for MIG and LIG, respectively) and Sq (9.5% and 5.3% for MIG and LIG, respectively), whereas in HIG the increase took place only in Sq (6.9%, p < 0.05). A calculation of effect sizes revealed greater strength gains in the MIG than in HIG or LIG. There were no significant differences between LIG and HIG training volume-induced strength gains. All the subjects in HIG were unable to fully accomplish the repetitions programmed at relative intensities greater than 90% of 1RM. The present results indicate that short-term resistance training using moderate volumes of high relative intensity tended to produce higher enhancements in weightlifting performance compared with low and high volumes of high relative training intensities of equal total volume in experienced, trained young weightlifters. Therefore, for the present population of weightlifters, it may be beneficial to use the MIG training protocol to improve the weightlifting program at least in a short-term (10 weeks) cycle of training.

Laser-Induced Graphene.

PubMed

Ye, Ruquan; James, Dustin K; Tour, James M

2018-06-20

Research on graphene abounds, from fundamental science to device applications. In pursuit of complementary morphologies, formation of graphene foams is often preferred over the native two-dimensional (2D) forms due to the higher available area. Graphene foams have been successfully prepared by several routes including chemical vapor deposition (CVD) methods and by wet-chemical approaches. For these methods, one often needs either high temperature furnaces and highly pure gases or large amounts of strong acids and oxidants. In 2014, using a commercial laser scribing system as found in most machine shops, a direct lasing of polyimide (PI) plastic films in the air converted the PI into 3D porous graphene, a material termed laser-induced graphene (LIG). This is a one-step method without the need for high-temperature reaction conditions, solvent, or subsequent treatments, and it affords graphene with many five-and seven-membered rings. With such an atomic arrangement, one might call LIG "kinetic graphene" since there is no annealing in the process that causes the rearrangement to the preferred all-six-membered-ring form. In this Account, we will first introduce the approaches that have been developed for making LIG and to control the morphology as either porous sheets or fibrils, and to control porosity, composition, and surface properties. The surfaces can be varied from being either superhydrophilic with a 0° contact angle with water to being superhydrophobic having >150° contact angle with water. While it was initially thought that the LIG process could only be performed on PI, it was later shown that a host of other polymeric substrates, nonpolymers, metal/plastic composites, and biodegradable and naturally occurring materials and foods could be used as platforms for generating LIG. Methods of preparation include roll-to-roll production for fabrication of in-plane electronics and two different 3D printing (additive manufacturing) routes to specific shapes of LIG monoliths using both laminated object manufacturing and powder bed fabrication methods. Use of the LIG in devices is performed very simply. This is showcased with high performance supercapacitors, fuel cell materials for oxygen reduction reactions, water splitting for both hydrogen and oxygen evolution reactions coming from the same plastic sheet, sensor devices, oil/water purification platforms, and finally applications in both passive and active biofilm inhibitors. So the ease of formation of LIG, its simple scale-up, and its utility for a range of applications highlights the easy transition of this substrate-bound graphene foam into commercial device platforms.

PIG2LIG-4FUTURE: a database

NASA Astrophysics Data System (ADS)

El Ouahabi, A.; Martrat, B.; Lopez, J. F.; Grimalt, J. O.

2012-04-01

The ability to simulate the rhythm of abrupt climate changes (ACCs) will depend on the availability of high quality palæoclimate databases with sufficient temporal resolution to make relevant inferences from a human perspective. This study presents the PIG2LIG-4FUTURE database (P2L-4F db). The philosophy behind is to facilitate access to data not only for the scientific community, but also for those outside this community and, in doing so, ensure that the data are as useful as possible to help in answering a challenging key question: What is the risk of ACCs in periods similar to the present one? The P2L-4F db identifies an intra- and inter-event stratigraphy. A breakdown of the events in the PIG (present interglacial, time period from which more information is available and it is reasonably well dated) is defined in order to (2) identify ACCs in the LIG (last interglacial, much less known and dated period) for (4) better evaluation of the likelihood of sudden shifts within warm climate behaviour (i.e. next centuries, FUTURE). For this db, both the PIG and the LIG include deglaciation and interglacial states and they are referred to by means of chronostratigraphy: (i) the PIG refers to the last 19 ka years, i.e. a precessional cycle should be complete within the next 5 ka years; (ii) the LIG is the time span between 133 ka and 109 ka years, i.e. a time slot of 24 ka years, roughly a precessional cycle. The db compiles comprehensive selected palæo-data retrieved from a variety of sources (http://www.ncdc.noaa.gov, http://www.pangaea.de and others) but also instrumental data, to validate reconstructions against observations (e.g. http://data.giss.nasa.gov, http://iridl.ldeo.columbia.edu, etc). The records included accomplish two simple criteria: they cover the time span of interest, specifically the PIG and the LIG periods, and have sufficient time resolution to distinguish between an ACC and a gradual event. The research has focussed on three main palæoarchives: (i) ice cores, because they have been the reference for ACCs for over half a century; (ii) stalagmites, because they are crucial for dating, particularly for the LIG; (iii) marine and continental sediments, because they have proven to be a powerful source of ACCs. The same response is not seen everywhere due to proxy and location effects (see-saws not only north-to-south between poles, but also tropics-to-poles and eastern-to-western gradients). However, by using global and regional stacks, PIG-like events have been located within the LIG period. The spatio-temporal pattern during several specific events will be discussed. For example, the results show that the PIG 8.2 ka-event was something akin to a dividing line, as it was a LIG event which occured at approximately 120 ka ago. Environment and climate were evidently very different before and after this type of events. Additionally, the 2.6 ka and 0.8 ka-events were more an exception than a rule, somewhat resembling a clear glacial inception initiated from 113 to 111 ka ago. However, ACCs within the PIG are not exactly the same as the ones for the LIG, either in intensity or rates of change. This fact is hardly surprising given that none of the triggers and sources of persistence were reproduced in an identical mode during both periods.

Structure-guided Mutational Analysis of the OB, HhH, and BRCT Domains of Escherichia coli DNA Ligase*S⃞

PubMed Central

Wang, Li Kai; Nair, Pravin A.; Shuman, Stewart

2008-01-01

NAD+-dependent DNA ligases (LigAs) are ubiquitous in bacteria and essential for growth. LigA enzymes have a modular structure in which a central catalytic core composed of nucleotidyltransferase and oligonucleotide-binding (OB) domains is linked via a tetracysteine zinc finger to distal helix-hairpin-helix (HhH) and BRCT (BRCA1-like C-terminal) domains. The OB and HhH domains contribute prominently to the protein clamp formed by LigA around nicked duplex DNA. Here we conducted a structure-function analysis of the OB and HhH domains of Escherichia coli LigA by alanine scanning and conservative substitutions, entailing 43 mutations at 22 amino acids. We thereby identified essential functional groups in the OB domain that engage the DNA phosphodiester backbone flanking the nick (Arg333); penetrate the minor grove and distort the nick (Val383 and Ile384); or stabilize the OB fold (Arg379). The essential constituents of the HhH domain include: four glycines (Gly455, Gly489, Gly521, Gly553), which bind the phosphate backbone across the minor groove at the outer margins of the LigA-DNA interface; Arg487, which penetrates the minor groove at the outer margin on the 3 ®-OH side of the nick; and Arg446, which promotes protein clamp formation via contacts to the nucleotidyltransferase domain. We find that the BRCT domain is required in its entirety for effective nick sealing and AMP-dependent supercoil relaxation. PMID:18515356

Kinetic mechanism of human DNA ligase I reveals magnesium-dependent changes in the rate-limiting step that compromise ligation efficiency.

PubMed

Taylor, Mark R; Conrad, John A; Wahl, Daniel; O'Brien, Patrick J

2011-07-01

DNA ligase I (LIG1) catalyzes the ligation of single-strand breaks to complete DNA replication and repair. The energy of ATP is used to form a new phosphodiester bond in DNA via a reaction mechanism that involves three distinct chemical steps: enzyme adenylylation, adenylyl transfer to DNA, and nick sealing. We used steady state and pre-steady state kinetics to characterize the minimal mechanism for DNA ligation catalyzed by human LIG1. The ATP dependence of the reaction indicates that LIG1 requires multiple Mg(2+) ions for catalysis and that an essential Mg(2+) ion binds more tightly to ATP than to the enzyme. Further dissection of the magnesium ion dependence of individual reaction steps revealed that the affinity for Mg(2+) changes along the reaction coordinate. At saturating concentrations of ATP and Mg(2+) ions, the three chemical steps occur at similar rates, and the efficiency of ligation is high. However, under conditions of limiting Mg(2+), the nick-sealing step becomes rate-limiting, and the adenylylated DNA intermediate is prematurely released into solution. Subsequent adenylylation of enzyme prevents rebinding to the adenylylated DNA intermediate comprising an Achilles' heel of LIG1. These ligase-generated 5'-adenylylated nicks constitute persistent breaks that are a threat to genomic stability if they are not repaired. The kinetic and thermodynamic framework that we have determined for LIG1 provides a starting point for understanding the mechanism and specificity of mammalian DNA ligases.

Structure-guided mutational analysis of the OB, HhH, and BRCT domains of Escherichia coli DNA ligase.

PubMed

Wang, Li Kai; Nair, Pravin A; Shuman, Stewart

2008-08-22

NAD(+)-dependent DNA ligases (LigAs) are ubiquitous in bacteria and essential for growth. LigA enzymes have a modular structure in which a central catalytic core composed of nucleotidyltransferase and oligonucleotide-binding (OB) domains is linked via a tetracysteine zinc finger to distal helix-hairpin-helix (HhH) and BRCT (BRCA1-like C-terminal) domains. The OB and HhH domains contribute prominently to the protein clamp formed by LigA around nicked duplex DNA. Here we conducted a structure-function analysis of the OB and HhH domains of Escherichia coli LigA by alanine scanning and conservative substitutions, entailing 43 mutations at 22 amino acids. We thereby identified essential functional groups in the OB domain that engage the DNA phosphodiester backbone flanking the nick (Arg(333)); penetrate the minor grove and distort the nick (Val(383) and Ile(384)); or stabilize the OB fold (Arg(379)). The essential constituents of the HhH domain include: four glycines (Gly(455), Gly(489), Gly(521), Gly(553)), which bind the phosphate backbone across the minor groove at the outer margins of the LigA-DNA interface; Arg(487), which penetrates the minor groove at the outer margin on the 3 (R)-OH side of the nick; and Arg(446), which promotes protein clamp formation via contacts to the nucleotidyltransferase domain. We find that the BRCT domain is required in its entirety for effective nick sealing and AMP-dependent supercoil relaxation.

A Defect in DNA Ligase4 Enhances the Frequency of TALEN-Mediated Targeted Mutagenesis in Rice1[OPEN

PubMed Central

Cermak, Tomas; Sugimoto, Kazuhiko; Saika, Hiroaki; Mori, Akiko; Osakabe, Keishi; Hamada, Masao; Katayose, Yuichi; Voytas, Daniel F.

2016-01-01

We have established methods for site-directed mutagenesis via transcription activator-like effector nucleases (TALENs) in the endogenous rice (Oryza sativa) waxy gene and demonstrated stable inheritance of TALEN-induced somatic mutations to the progeny. To analyze the role of classical nonhomologous end joining (cNHEJ) and alternative nonhomologous end joining (altNHEJ) pathways in TALEN-induced mutagenesis in plant cells, we investigated whether a lack of DNA Ligase4 (Lig4) affects the kinetics of TALEN-induced double-strand break repair in rice cells. Deep-sequencing analysis revealed that the frequency of all types of mutations, namely deletion, insertion, combination of insertion with deletion, and substitution, in lig4 null mutant calli was higher than that in a lig4 heterozygous mutant or the wild type. In addition, the ratio of large deletions (greater than 10 bp) and deletions repaired by microhomology-mediated end joining (MMEJ) to total deletion mutations in lig4 null mutant calli was higher than that in the lig4 heterozygous mutant or wild type. Furthermore, almost all insertions (2 bp or greater) were shown to be processed via copy and paste of one or more regions around the TALENs cleavage site and rejoined via MMEJ regardless of genetic background. Taken together, our findings indicate that the dysfunction of cNHEJ leads to a shift in the repair pathway from cNHEJ to altNHEJ or synthesis-dependent strand annealing. PMID:26668331

Coupled Long-Term Evolution of Climate and the Greenland Ice Sheet During the Last Interglacial and Implications for the Future

NASA Astrophysics Data System (ADS)

Otto-Bliesner, B. L.; Lofverstrom, M.; Lipscomb, W.; Fyke, J. G.; Marshall, S.; Sacks, B.

2017-12-01

The Greenland Ice Sheet (GrIS) is expected to contribute increasingly to global sea level rise by the end of this century, and potentially several meters in this millennium, but still with considerable uncertainty. The rate of Greenland melt will impact on regional sea levels. The Last Interglacial (LIG, 129 ka to 116 ka) is recognized as an important period for testing our knowledge of climate-ice sheet interactions in warm climate states. Although the LIG was discussed in the First Assessment Report of the IPCC, it gained more prominence in the IPCC Fourth and Fifth Assessment (AR4 and AR5) with reconstructions highlighting that global mean sea level was at least 5 m higher (but probably no more than 10 m higher) than present for several thousand years during the LIG. Model results assessed for the AR5 suggest a sea level contribution of 1.4 to 4.3 m from the GrIS. These model simulations, though, did not include all the feedbacks of the climate system and the GrIS. Here, we examine the response of the Arctic climate system and the GrIS in simulations with the Community Earth System Model (CESM) fully coupled to the Community Ice Sheet Model (CISM), using a surface energy balance scheme and without bias corrections. The analysis focuses on how the GrIS responds to the imposed high boreal summer insolation of the LIG and in addition, to the long-term feedbacks of high-latitude vegetation changes. Results will highlight the evolution of the ice sheet and the surface mass balance (patterns of ablation and accumulation) as compared to data-based reconstructions for the LIG. We conclude with a discussion on how the LIG may be informative as a potential process analogue for the GrIS response for future centuries to come.

Characterisation of betalain biosynthesis in Parakeelya flowers identifies the key biosynthetic gene DOD as belonging to an expanded LigB gene family that is conserved in betalain-producing species

PubMed Central

Chung, Hsiao-Hang; Schwinn, Kathy E.; Ngo, Hanh M.; Lewis, David H.; Massey, Baxter; Calcott, Kate E.; Crowhurst, Ross; Joyce, Daryl C.; Gould, Kevin S.; Davies, Kevin M.; Harrison, Dion K.

2015-01-01

Plant betalain pigments are intriguing because they are restricted to the Caryophyllales and are mutually exclusive with the more common anthocyanins. However, betalain biosynthesis is poorly understood compared to that of anthocyanins. In this study, betalain production and betalain-related genes were characterized in Parakeelya mirabilis (Montiaceae). RT-PCR and transcriptomics identified three sequences related to the key biosynthetic enzyme Dopa 4,5-dioxgenase (DOD). In addition to a LigB gene similar to that of non-Caryophyllales species (Class I genes), two other P. mirabilis LigB genes were found (DOD and DOD-like, termed Class II). PmDOD and PmDOD-like had 70% amino acid identity. Only PmDOD was implicated in betalain synthesis based on transient assays of enzyme activity and correlation of transcript abundance to spatio-temporal betalain accumulation. The role of PmDOD-like remains unknown. The striking pigment patterning of the flowers was due to distinct zones of red betacyanin and yellow betaxanthin production. The major betacyanin was the unglycosylated betanidin rather than the commonly found glycosides, an occurrence for which there are a few previous reports. The white petal zones lacked pigment but had DOD activity suggesting alternate regulation of the pathway in this tissue. DOD and DOD-like sequences were also identified in other betalain-producing species but not in examples of anthocyanin-producing Caryophyllales or non-Caryophyllales species. A Class I LigB sequence from the anthocyanin-producing Caryophyllaceae species Dianthus superbus and two DOD-like sequences from the Amaranthaceae species Beta vulgaris and Ptilotus spp. did not show DOD activity in the transient assay. The additional sequences suggests that DOD is part of a larger LigB gene family in betalain-producing Caryophyllales taxa, and the tandem genomic arrangement of two of the three B. vulgaris LigB genes suggests the involvement of duplication in the gene family evolution. PMID:26217353

Research in the Optical Sciences.

DTIC Science & Technology

1981-01-30

technology, as mirrors for laser weapons, and as protec- tive coatings in laser warfare. Three phases of the study were considered: 91. Laboratory...performance of simple metal coatings used on concentrating and flat-plate mirrors subject to high solar flux and heat, and on military mirrors used for...atI i :-a;t ;oil Cutiponlit -1of th >na"Cl I I C ’k lig ht cani be indi(ependent iv measured. 12 The scattering levels of most of the studied mirrors

Proceedings of a Seminar on Attaining Water Quality Goals through Water Management Procedures, 17-18 February 1982, Dallas, Texas,

DTIC Science & Technology

1982-02-01

slightly above the level of detection. In both projects low-level accumulation of petroleum hydrocarbons was observed. Because of the complex nature of... petroleum hydrocarbons , PCB, total DDT, Cd and lig in test and control organisms surviving a 10-day, solid phlase bioassay for project A. Organisms...of petroleum hydrocarbons , PCB, total DDT, Cd and Hig in test and control organisms surviving a 10-day solid phase bioassay for project B. Organisms

Mixed infection of Sida jamaicensis in Jamaica reveals the presence of three recombinant begomovirus DNA A components.

PubMed

Stewart, Cheryl; Kon, Tatsuya; Rojas, Maria; Graham, André; Martin, Darren; Gilbertson, Robert; Roye, Marcia

2014-09-01

Begomoviruses impose serious constraints on agriculture throughout the temperate, tropical and subtropical regions. Previously, we characterised a sida golden yellow vein virus isolate, SiGYVV-[JM:Lig2:08] (HQ009519-20) from a symptomatic Sida jamaicensis plant. With the aim of establishing whether it was hosting a mixed infection that could facilitate recombination, PCR-RFLP was done on DNA extracted from this plant, and the results suggested the presence of two additional genetically distinct DNA-A molecules. Sequence analysis of these two DNA-A molecules (relying on BLAST searches and the CLUSTAL V algorithm within the DNASTAR MegAlign module) revealed that they belonged to novel species, and we have tentatively named these viruses sida golden mosaic Braco virus-[Jamaica:Liguanea:2008] and sida golden mosaic Liguanea virus-[Jamaica:1:2008]. Using RDP4 (recombination detection program), we determined that all three viruses were recombinant, with bases ~10 to ~440 of both SiGMLigV-[JM:Lig:08] and SiGYVV-[JM:Lig2:08] having been derived from a relative of SiGMBV-[JM:Lig:08] (P<2.070×10(-7) for all seven of the recombination detection methods). SiGMBV-[JM:Lig:08] was itself a product of recombination, deriving bases ~490-1195 from a virus that was ~92% similar to malvastrum yellow mosaic Helshire virus. Phylogenetically, these DNA-A components are most closely related to those of malvaceous weed-infecting begomoviruses from Jamaica, Cuba, Florida and Mexico. The SiGMBV DNA-A was able to elicit symptomatic infection in N. benthamiana.

Detailed analysis of targeted gene mutations caused by the Platinum-Fungal TALENs in Aspergillus oryzae RIB40 strain and a ligD disruptant.

PubMed

Mizutani, Osamu; Arazoe, Takayuki; Toshida, Kenji; Hayashi, Risa; Ohsato, Shuichi; Sakuma, Tetsushi; Yamamoto, Takashi; Kuwata, Shigeru; Yamada, Osamu

2017-03-01

Transcription activator-like effector nucleases (TALENs), which can generate DNA double-strand breaks at specific sites in the desired genome locus, have been used in many organisms as a tool for genome editing. In Aspergilli, including Aspergillus oryzae, however, the use of TALENs has not been validated. In this study, we performed genome editing of A. oryzae wild-type strain via error of nonhomologous end-joining (NHEJ) repair by transient expression of high-efficiency Platinum-Fungal TALENs (PtFg TALENs). Targeted mutations were observed as various mutation patterns. In particular, approximately half of the PtFg TALEN-mediated deletion mutants had deletions larger than 1 kb in the TALEN-targeting region. We also conducted PtFg TALEN-based genome editing in A. oryzae ligD disruptant (ΔligD) lacking the ligD gene involved in the final step of the NHEJ repair and found that mutations were still obtained as well as wild-type. In this case, the ratio of the large deletions reduced compared to PtFg TALEN-based genome editing in the wild-type. In conclusion, we demonstrate that PtFg TALENs are sufficiently functional to cause genome editing via error of NHEJ in A. oryzae. In addition, we reveal that genome editing using TALENs in A. oryzae tends to cause large deletions at the target region, which were partly suppressed by deletion of ligD. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Structural and Biochemical Characterization of the Early and Late Enzymes in the Lignin β-Aryl Ether Cleavage Pathway from Sphingobium sp. SYK-6.

PubMed

Pereira, Jose Henrique; Heins, Richard A; Gall, Daniel L; McAndrew, Ryan P; Deng, Kai; Holland, Keefe C; Donohue, Timothy J; Noguera, Daniel R; Simmons, Blake A; Sale, Kenneth L; Ralph, John; Adams, Paul D

2016-05-06

There has been great progress in the development of technology for the conversion of lignocellulosic biomass to sugars and subsequent fermentation to fuels. However, plant lignin remains an untapped source of materials for production of fuels or high value chemicals. Biological cleavage of lignin has been well characterized in fungi, in which enzymes that create free radical intermediates are used to degrade this material. In contrast, a catabolic pathway for the stereospecific cleavage of β-aryl ether units that are found in lignin has been identified in Sphingobium sp. SYK-6 bacteria. β-Aryl ether units are typically abundant in lignin, corresponding to 50-70% of all of the intermonomer linkages. Consequently, a comprehensive understanding of enzymatic β-aryl ether (β-ether) cleavage is important for future efforts to biologically process lignin and its breakdown products. The crystal structures and biochemical characterization of the NAD-dependent dehydrogenases (LigD, LigO, and LigL) and the glutathione-dependent lyase LigG provide new insights into the early and late enzymes in the β-ether degradation pathway. We present detailed information on the cofactor and substrate binding sites and on the catalytic mechanisms of these enzymes, comparing them with other known members of their respective families. Information on the Lig enzymes provides new insight into their catalysis mechanisms and can inform future strategies for using aromatic oligomers derived from plant lignin as a source of valuable aromatic compounds for biofuels and other bioproducts. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Structural and Biochemical Characterization of the Early and Late Enzymes in the Lignin β-Aryl Ether Cleavage Pathway from Sphingobium sp. SYK-6

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pereira, Jose Henrique; Heins, Richard A.; Gall, Daniel L.

There has been great progress in the development of technology for the conversion of lignocellulosic biomass to sugars and subsequent fermentation to fuels. However, plant lignin remains an untapped source of materials for production of fuels or high value chemicals. Biological cleavage of lignin has been well characterized in fungi, in which enzymes that create free radical intermediates are used to degrade this material. In contrast, a catabolic pathway for the stereospecific cleavage of β-aryl ether units that are found in lignin has been identified in Sphingobium sp. SYK-6 bacteria. β-Aryl ether units are typically abundant in lignin, corresponding tomore » 50–70% of all of the intermonomer linkages. Consequently, a comprehensive understanding of enzymatic β-aryl ether (β-ether) cleavage is important for future efforts to biologically process lignin and its breakdown products. The crystal structures and biochemical characterization of the NAD-dependent dehydrogenases (LigD, LigO, and LigL) and the glutathione-dependent lyase LigG provide new insights into the early and late enzymes in the β-ether degradation pathway. We present detailed information on the cofactor and substrate binding sites and on the catalytic mechanisms of these enzymes, comparing them with other known members of their respective families. Information on the Lig enzymes provides new insight into their catalysis mechanisms and can inform future strategies for using aromatic oligomers derived from plant lignin as a source of valuable aromatic compounds for biofuels and other bioproducts.« less

Structural and Biochemical Characterization of the Early and Late Enzymes in the Lignin β-Aryl Ether Cleavage Pathway from Sphingobium sp. SYK-6

DOE PAGES

Pereira, Jose Henrique; Heins, Richard A.; Gall, Daniel L.; ...

2016-03-03

There has been great progress in the development of technology for the conversion of lignocellulosic biomass to sugars and subsequent fermentation to fuels. However, plant lignin remains an untapped source of materials for production of fuels or high value chemicals. Biological cleavage of lignin has been well characterized in fungi, in which enzymes that create free radical intermediates are used to degrade this material. In contrast, a catabolic pathway for the stereospecific cleavage of β-aryl ether units that are found in lignin has been identified in Sphingobium sp. SYK-6 bacteria. β-Aryl ether units are typically abundant in lignin, corresponding tomore » 50–70% of all of the intermonomer linkages. Consequently, a comprehensive understanding of enzymatic β-aryl ether (β-ether) cleavage is important for future efforts to biologically process lignin and its breakdown products. The crystal structures and biochemical characterization of the NAD-dependent dehydrogenases (LigD, LigO, and LigL) and the glutathione-dependent lyase LigG provide new insights into the early and late enzymes in the β-ether degradation pathway. We present detailed information on the cofactor and substrate binding sites and on the catalytic mechanisms of these enzymes, comparing them with other known members of their respective families. Information on the Lig enzymes provides new insight into their catalysis mechanisms and can inform future strategies for using aromatic oligomers derived from plant lignin as a source of valuable aromatic compounds for biofuels and other bioproducts.« less

Structural and Biochemical Characterization of the Early and Late Enzymes in the Lignin β-Aryl Ether Cleavage Pathway from Sphingobium sp. SYK-6*

PubMed Central

Pereira, Jose Henrique; Heins, Richard A.; Gall, Daniel L.; McAndrew, Ryan P.; Deng, Kai; Holland, Keefe C.; Donohue, Timothy J.; Noguera, Daniel R.; Simmons, Blake A.; Sale, Kenneth L.; Ralph, John; Adams, Paul D.

2016-01-01

There has been great progress in the development of technology for the conversion of lignocellulosic biomass to sugars and subsequent fermentation to fuels. However, plant lignin remains an untapped source of materials for production of fuels or high value chemicals. Biological cleavage of lignin has been well characterized in fungi, in which enzymes that create free radical intermediates are used to degrade this material. In contrast, a catabolic pathway for the stereospecific cleavage of β-aryl ether units that are found in lignin has been identified in Sphingobium sp. SYK-6 bacteria. β-Aryl ether units are typically abundant in lignin, corresponding to 50–70% of all of the intermonomer linkages. Consequently, a comprehensive understanding of enzymatic β-aryl ether (β-ether) cleavage is important for future efforts to biologically process lignin and its breakdown products. The crystal structures and biochemical characterization of the NAD-dependent dehydrogenases (LigD, LigO, and LigL) and the glutathione-dependent lyase LigG provide new insights into the early and late enzymes in the β-ether degradation pathway. We present detailed information on the cofactor and substrate binding sites and on the catalytic mechanisms of these enzymes, comparing them with other known members of their respective families. Information on the Lig enzymes provides new insight into their catalysis mechanisms and can inform future strategies for using aromatic oligomers derived from plant lignin as a source of valuable aromatic compounds for biofuels and other bioproducts. PMID:26940872

Telomere-Internal Double-Strand Breaks Are Repaired by Homologous Recombination and PARP1/Lig3-Dependent End-Joining.

PubMed

Doksani, Ylli; de Lange, Titia

2016-11-01

Shelterin protects chromosome ends from the DNA damage response. Although the mechanism of telomere protection has been studied extensively, the fate of double-strand breaks (DSBs) inside telomeres is not known. Here, we report that telomere-internal FokI-induced DSBs activate ATM kinase-dependent signaling in S-phase but are well tolerated and repaired efficiently. Homologous recombination contributes to repair, leading to increased telomere length heterogeneity typical of the alternative lengthening of telomeres (ALT) pathway. Furthermore, cells accumulate extra chromosomal telomeric signals (ECTS), a second hallmark of ALT. Telomere-internal DSBs are also repaired by a PARP1- and Ligase3-dependent reaction, suggesting alternative non-homologous end-joining (alt-NHEJ), which relies on microhomology at DSBs. However, as resected telomere-internal DSBs have perfect homology, their PARP1/Lig3-dependent end-joining may be more akin to single strand break repair. We conclude that shelterin does not repress ATM kinase signaling or DSB repair at telomere-internal sites, thereby allowing DNA repair to maintain telomere integrity. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Cost-effectiveness of community vegetable gardens for people living with HIV in Zimbabwe.

PubMed

Puett, Chloe; Salpéteur, Cécile; Lacroix, Elisabeth; Zimunya, Simbarashe Dennis; Israël, Anne-Dominique; Aït-Aïssa, Myriam

2014-01-01

There is little evidence to date of the potential impact of vegetable gardens on people living with HIV (PLHIV), who often suffer from social and economic losses due to the disease. From 2008 through 2011, Action Contre la Faim France (ACF) implemented a project in Chipinge District, eastern Zimbabwe, providing low-input vegetable gardens (LIGs) to households of PLHIV. Program partners included Médecins du Monde, which provided medical support, and Zimbabwe's Agricultural Extension Service, which supported vegetable cultivation. A survey conducted at the end of the program found LIG participants to have higher Food Consumption Scores (FCS) and Household Dietary Diversity Scores (HDDS) relative to comparator households of PLHIV receiving other support programs. This study assessed the incremental cost-effectiveness of LIGs to improve FCS and HDDS of PLHIV compared to other support programs. This analysis used an activity-based cost model, and combined ACF accounting data with estimates of partner and beneficiary costs derived using an ingredients approach to build an estimate of total program resource use. A societal perspective was adopted to encompass costs to beneficiary households, including their opportunity costs and an estimate of their income earned from vegetable sales. Qualitative methods were used to assess program benefits to beneficiary households. Effectiveness data was taken from a previously-conducted survey. Providing LIGs to PLHIV cost an additional 8,299 EUR per household with adequate FCS and 12,456 EUR per household with HDDS in the upper tertile, relative to comparator households of PLHIV receiving other support programs. Beneficiaries cited multiple tangible and intangible benefits from LIGs, and over 80% of gardens observed were still functioning more than one year after the program had finished. Cost outcomes were 20-30 times Zimbabwe's per capita GDP, and unlikely to be affordable within government services. This analysis concludes that LIGs are not cost-effective or affordable relative to other interventions for improving health and nutrition status of PLHIV. Nonetheless, given the myriad benefits acquired by participant households, such programs hold important potential to improve quality of life and reduce stigma against PLHIV.

Near-field sea-level variability in northwest Europe and ice sheet stability during the last interglacial

NASA Astrophysics Data System (ADS)

Long, A. J.; Barlow, N. L. M.; Busschers, F. S.; Cohen, K. M.; Gehrels, W. R.; Wake, L. M.

2015-10-01

Global sea level during the Last Interglacial (LIG, Marine Isotope Sub-stage 5e) peaked between c. 5.5 and 9 m above present, implying significant melt from Greenland and Antarctica. Relative sea level (RSL) observations from several far- and intermediate-field sites suggest abrupt fluctuations or jumps in RSL during the LIG highstand that require one or more episodes of ice-sheet collapse and regrowth. Such events should be manifest as unique sea-level fingerprints, recorded in far-, intermediate- and near-field sites depending on the source(s) of ice-mass change involved. To date, though, no coherent evidence of such fluctuations has been reported from near-field RSL studies in northwest Europe. This is an important problem because RSL fluctuations during the LIG are portrayed as warning signs for how polar ice sheets may behave in a future, warmer than present, world. Here we review the evidence for RSL change during the LIG using stratigraphic data from the best resolved highstand records that exist in the near-field of northwest Europe, from a range of settings that include lagoonal, shallow marine, tidal flat, salt marsh and brackish-water fluviatile environments. Consideration of previously published stratigraphic records from two sites in the Eemian coastal-marine embayment that existed in the central Netherlands, yields no clear indications for abrupt RSL change during the attainment of the near-field highstand. Nor do we find any such indications common to other records from countries bordering the North Sea, the Baltic Sea and the White Sea. Two modelling experiments that explore the global signal of hypothetical sea-level oscillations caused by partial collapse and regrowth of either the Greenland or Antarctic LIG ice-sheet, show that the North Sea region is relatively insensitive to mass changes sourced from Greenland but should clearly register events with an Antarctic origin, especially those that occur late in the LIG. The lack of evidence for abrupt sea-level fluctuations at this time in northwest Europe concurs with a lack of clear near-field evidence for ice sheet collapse.

Cost-effectiveness of community vegetable gardens for people living with HIV in Zimbabwe

PubMed Central

2014-01-01

Background There is little evidence to date of the potential impact of vegetable gardens on people living with HIV (PLHIV), who often suffer from social and economic losses due to the disease. From 2008 through 2011, Action Contre la Faim France (ACF) implemented a project in Chipinge District, eastern Zimbabwe, providing low-input vegetable gardens (LIGs) to households of PLHIV. Program partners included Médecins du Monde, which provided medical support, and Zimbabwe's Agricultural Extension Service, which supported vegetable cultivation. A survey conducted at the end of the program found LIG participants to have higher Food Consumption Scores (FCS) and Household Dietary Diversity Scores (HDDS) relative to comparator households of PLHIV receiving other support programs. This study assessed the incremental cost-effectiveness of LIGs to improve FCS and HDDS of PLHIV compared to other support programs. Methods This analysis used an activity-based cost model, and combined ACF accounting data with estimates of partner and beneficiary costs derived using an ingredients approach to build an estimate of total program resource use. A societal perspective was adopted to encompass costs to beneficiary households, including their opportunity costs and an estimate of their income earned from vegetable sales. Qualitative methods were used to assess program benefits to beneficiary households. Effectiveness data was taken from a previously-conducted survey. Results Providing LIGs to PLHIV cost an additional 8,299 EUR per household with adequate FCS and 12,456 EUR per household with HDDS in the upper tertile, relative to comparator households of PLHIV receiving other support programs. Beneficiaries cited multiple tangible and intangible benefits from LIGs, and over 80% of gardens observed were still functioning more than one year after the program had finished. Conclusions Cost outcomes were 20–30 times Zimbabwe's per capita GDP, and unlikely to be affordable within government services. This analysis concludes that LIGs are not cost-effective or affordable relative to other interventions for improving health and nutrition status of PLHIV. Nonetheless, given the myriad benefits acquired by participant households, such programs hold important potential to improve quality of life and reduce stigma against PLHIV. PMID:24834014

Metal ions from S‐PRG filler have the potential to prevent periodontal disease

PubMed Central

Iwamatsu‐Kobayashi, Yoko; Abe, Syouta; Fujieda, Yoshiyasu; Orimoto, Ai; Kanehira, Masafumi; Handa, Keisuke; Venkataiah, Venkata Suresh; Zou, Wei; Ishikawa, Masaki

2017-01-01

Abstract The surface pre‐reacted glass ionomer (S‐PRG) filler, a component of composite resin, is capable of releasing metal ions that possess antibacterial activity against caries and periodontal pathogens. Although S‐PRG has been suggested to be involved in oral disease prevention, no reports have been published regarding its preventive effect on periodontal disease in vivo. The present study investigated whether the eluate from S‐PRG (S‐PRG eluate) has a suppressive effect on tissue destruction induced in a mouse model of ligature‐induced periodontal disease. Twenty‐seven C57BL/6 mice were divided into three groups of nine animals each, no ligature group (Lig(−)), ligature group (Lig(+)S‐PRG(−)) and ligature with S‐PRG eluate group (Lig(+)S‐PRG(+)). Alveolar bone loss was evaluated using micro‐computed tomography scanning. Histologic changes were detected by hematoxylin and eosin staining. The infiltration of inflammatory cells was assessed by Ly6G and F4/80 staining immunohistochemically. The distribution of metal ions was detected by time‐of‐flight secondary ion mass spectrometry. S‐PRG eluate clearly inhibited alveolar bone loss and bone density. The histological analysis revealed that S‐PRG eluate reduced destruction of the collagen bundle in the periodontal ligament and the infiltration of inflammatory cells. Immunohistochemical analysis showed that the S‐PRG eluate significantly suppressed the number of infiltrating neutrophils and macrophages. Time‐of‐flight secondary ion mass spectrometry analysis revealed that more boron ions were present in the Lig(+)S‐PRG(+) group than in the Lig(+)S‐PRG(−) group. Our results suggest that the S‐PRG eluate has a preventive effect against tissue destruction in periodontal disease through its anti‐inflammatory effects in vivo. PMID:29744190

Boundary layer friction of solvate ionic liquids as a function of potential.

PubMed

Li, Hua; Rutland, Mark W; Watanabe, Masayoshi; Atkin, Rob

2017-07-01

Atomic force microscopy (AFM) has been used to investigate the potential dependent boundary layer friction at solvate ionic liquid (SIL)-highly ordered pyrolytic graphite (HOPG) and SIL-Au(111) interfaces. Friction trace and retrace loops of lithium tetraglyme bis(trifluoromethylsulfonyl)amide (Li(G4) TFSI) at HOPG present clearer stick-slip events at negative potentials than at positive potentials, indicating that a Li + cation layer adsorbed to the HOPG lattice at negative potentials which enhances stick-slip events. The boundary layer friction data for Li(G4) TFSI shows that at HOPG, friction forces at all potentials are low. The TFSI - anion rich boundary layer at positive potentials is more lubricating than the Li + cation rich boundary layer at negative potentials. These results suggest that boundary layers at all potentials are smooth and energy is predominantly dissipated via stick-slip events. In contrast, friction at Au(111) for Li(G4) TFSI is significantly higher at positive potentials than at negative potentials, which is comparable to that at HOPG at the same potential. The similarity of boundary layer friction at negatively charged HOPG and Au(111) surfaces indicates that the boundary layer compositions are similar and rich in Li + cations for both surfaces at negative potentials. However, at Au(111), the TFSI - rich boundary layer is less lubricating than the Li + rich boundary layer, which implies that anion reorientations rather than stick-slip events are the predominant energy dissipation pathways. This is confirmed by the boundary friction of Li(G4) NO 3 at Au(111), which shows similar friction to Li(G4) TFSI at negative potentials due to the same cation rich boundary layer composition, but even higher friction at positive potentials, due to higher energy dissipation in the NO 3 - rich boundary layer.

Highly efficient gene targeting in Aspergillus oryzae industrial strains under ligD mutation introduced by genome editing: Strain-specific differences in the effects of deleting EcdR, the negative regulator of sclerotia formation.

PubMed

Nakamura, Hidetoshi; Katayama, Takuya; Okabe, Tomoya; Iwashita, Kazuhiro; Fujii, Wataru; Kitamoto, Katsuhiko; Maruyama, Jun-Ichi

2017-07-11

Numerous strains of Aspergillus oryzae are industrially used for Japanese traditional fermentation and for the production of enzymes and heterologous proteins. In A. oryzae, deletion of the ku70 or ligD genes involved in non-homologous end joining (NHEJ) has allowed high gene targeting efficiency. However, this strategy has been mainly applied under the genetic background of the A. oryzae wild strain RIB40, and it would be laborious to delete the NHEJ genes in many A. oryzae industrial strains, probably due to their low gene targeting efficiency. In the present study, we generated ligD mutants from the A. oryzae industrial strains by employing the CRISPR/Cas9 system, which we previously developed as a genome editing method. Uridine/uracil auxotrophic strains were generated by deletion of the pyrG gene, which was subsequently used as a selective marker. We examined the gene targeting efficiency with the ecdR gene, of which deletion was reported to induce sclerotia formation under the genetic background of the strain RIB40. As expected, the deletion efficiencies were high, around 60~80%, in the ligD mutants of industrial strains. Intriguingly, the effects of the ecdR deletion on sclerotia formation varied depending on the strains, and we found sclerotia-like structures under the background of the industrial strains, which have never been reported to form sclerotia. The present study demonstrates that introducing ligD mutation by genome editing is an effective method allowing high gene targeting efficiency in A. oryzae industrial strains.

Saccharomyces boulardii improves humoral immune response to DNA vaccines against leptospirosis.

PubMed

Silveira, Marcelle Moura; Conceição, Fabricio Rochedo; Mendonça, Marcelo; Moreira, Gustavo Marçal Schmidt Garcia; Da Cunha, Carlos Eduardo Pouey; Conrad, Neida Lucia; Oliveira, Patrícia Diaz de; Hartwig, Daiane Drawanz; De Leon, Priscila Marques Moura; Moreira, Ângela Nunes

2017-02-01

Saccharomyces boulardii may improve the immune response by enhancing the production of anti-inflammatory cytokines, T-cell proliferation and dendritic cell activation. The immunomodulator effect of this probiotic has never been tested with DNA vaccines, which frequently induce low antibody titers. This study evaluated the capacity of Saccharomyces boulardii to improve the humoral and cellular immune responses using DNA vaccines coding for the leptospiral protein fragments LigAni and LigBrep. BALB/c mice were fed with rodent-specific feed containing 108 c.f.u. of Saccharomycesboulardii per gram. Animals were immunized three times intramuscularly with 100 µg of pTARGET plasmids containing the coding sequences for the above mentioned proteins. Antibody titers were measured by indirect ELISA. Expression levels of IL-4, IL-10, IL-12, IL-17, IFN-γ and TGF-β were determined by quantitative real-time PCR from RNA extracted from whole blood, after an intraperitoneal boost with 50 µg of the recombinant proteins.Results/Key findings. Antibody titers increased significantly after the second and third application when pTARGET/ligAni and pTARGET/ligBrep were used to vaccinate the animals in comparison with the control group (P<0.05). In addition, there was a significant increase in the expression of the IL-10 in mice immunized with pTARGET/ligBrep and fed with Saccharomyces boulardii. The results suggested that Saccharomyces boulardii has an immunomodulator effect in DNA vaccines, mainly by stimulating the humoral response, which is often limited in this kind of vaccine. Therefore, the use of Saccharomyces boulardii as immunomodulator represents a new alternative strategy for more efficient DNA vaccination.

Presequence-Independent Mitochondrial Import of DNA Ligase Facilitates Establishment of Cell Lines with Reduced mtDNA Copy Number

PubMed Central

Spadafora, Domenico; Kozhukhar, Natalia; Alexeyev, Mikhail F.

2016-01-01

Due to the essential role played by mitochondrial DNA (mtDNA) in cellular physiology and bioenergetics, methods for establishing cell lines with altered mtDNA content are of considerable interest. Here, we report evidence for the existence in mammalian cells of a novel, low- efficiency, presequence-independent pathway for mitochondrial protein import, which facilitates mitochondrial uptake of such proteins as Chlorella virus ligase (ChVlig) and Escherichia coli LigA. Mouse cells engineered to depend on this pathway for mitochondrial import of the LigA protein for mtDNA maintenance had severely (up to >90%) reduced mtDNA content. These observations were used to establish a method for the generation of mouse cell lines with reduced mtDNA copy number by, first, transducing them with a retrovirus encoding LigA, and then inactivating in these transductants endogenous Lig3 with CRISPR-Cas9. Interestingly, mtDNA depletion to an average level of one copy per cell proceeds faster in cells engineered to maintain mtDNA at low copy number. This makes a low-mtDNA copy number phenotype resulting from dependence on mitochondrial import of DNA ligase through presequence-independent pathway potentially useful for rapidly shifting mtDNA heteroplasmy through partial mtDNA depletion. PMID:27031233

Extreme Growth Failure is a Common Presentation of Ligase IV Deficiency

PubMed Central

Murray, Jennie E; Bicknell, Louise S; Yigit, Gökhan; Duker, Angela L; van Kogelenberg, Margriet; Haghayegh, Sara; Wieczorek, Dagmar; Kayserili, Hülya; Albert, Michael H; Wise, Carol A; Brandon, January; Kleefstra, Tjitske; Warris, Adilia; van der Flier, Michiel; Bamforth, J Steven; Doonanco, Kurston; Adès, Lesley; Ma, Alan; Field, Michael; Johnson, Diana; Shackley, Fiona; Firth, Helen; Woods, C Geoffrey; Nürnberg, Peter; Gatti, Richard A; Hurles, Matthew; Bober, Michael B; Wollnik, Bernd; Jackson, Andrew P

2014-01-01

Ligase IV syndrome is a rare differential diagnosis for Nijmegen breakage syndrome owing to a shared predisposition to lympho-reticular malignancies, significant microcephaly, and radiation hypersensitivity. Only 16 cases with mutations in LIG4 have been described to date with phenotypes varying from malignancy in developmentally normal individuals, to severe combined immunodeficiency and early mortality. Here, we report the identification of biallelic truncating LIG4 mutations in 11 patients with microcephalic primordial dwarfism presenting with restricted prenatal growth and extreme postnatal global growth failure (average OFC −10.1 s.d., height −5.1 s.d.). Subsequently, most patients developed thrombocytopenia and leucopenia later in childhood and many were found to have previously unrecognized immunodeficiency following molecular diagnosis. None have yet developed malignancy, though all patients tested had cellular radiosensitivity. A genotype–phenotype correlation was also noted with position of truncating mutations corresponding to disease severity. This work extends the phenotypic spectrum associated with LIG4 mutations, establishing that extreme growth retardation with microcephaly is a common presentation of bilallelic truncating mutations. Such growth failure is therefore sufficient to consider a diagnosis of LIG4 deficiency and early recognition of such cases is important as bone marrow failure, immunodeficiency, and sometimes malignancy are long term sequelae of this disorder. PMID:24123394

New insights on laser-induced graphene electrodes for flexible supercapacitors: tunable morphology and physical properties.

PubMed

Lamberti, Andrea; Perrucci, Francesco; Caprioli, Matteo; Serrapede, Mara; Fontana, Marco; Bianco, Stefano; Ferrero, Sergio; Tresso, Elena

2017-04-28

In certain polymers the graphenization of carbon atoms can be obtained by laser writing owing to the easy absorption of long-wavelength radiation, which generates photo-thermal effects. On a polyimide surface this process allows the formation of a nanostructured and porous carbon network known as laser-induced graphene (LIG). Herein we report on the effect of the process parameters on the morphology and physical properties of LIG nanostructures. We show that the scan speed and the frequency of the incident radiation affect the gas evolution, inducing different structure rearrangements, an interesting nitrogen self-doping phenomenon and consequently different conduction properties. The materials were characterized by infrared and Raman spectroscopy, XPS elemental analysis, electron microscopy and electrical/electrochemical measurements. In particular the samples were tested as interdigitated electrodes into electrochemical supercapacitors and the optimized LIG arrangement was tested in parallel and series supercapacitor configurations to allow power exploitation.

Laminated Object Manufacturing of 3D-Printed Laser-Induced Graphene Foams.

PubMed

Luong, Duy Xuan; Subramanian, Ajay K; Silva, Gladys A Lopez; Yoon, Jongwon; Cofer, Savannah; Yang, Kaichun; Owuor, Peter Samora; Wang, Tuo; Wang, Zhe; Lou, Jun; Ajayan, Pulickel M; Tour, James M

2018-05-29

Laser-induced graphene (LIG), a graphene structure synthesized by a one-step process through laser treatment of commercial polyimide (PI) film in an ambient atmosphere, has been shown to be a versatile material in applications ranging from energy storage to water treatment. However, the process as developed produces only a 2D product on the PI substrate. Here, a 3D LIG foam printing process is developed on the basis of laminated object manufacturing, a widely used additive-manufacturing technique. A subtractive laser-milling process to yield further refinements to the 3D structures is also developed and shown here. By combining both techniques, various 3D graphene objects are printed. The LIG foams show good electrical conductivity and mechanical strength, as well as viability in various energy storage and flexible electronic sensor applications. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Using a Glacial Isostatic Adjustment model to investigate the contribution of the Antarctic and Greenland Ice sheet to the Last Interglacial Sea Level.

NASA Astrophysics Data System (ADS)

Bradley, Sarah; Hindmarsh, Richard C. A.

2014-05-01

Eustatic Sea Level during the Last interglacial (LIG) is likely to have been 4- 6 m higher than present day, with the observed relative sea level (RSL) at numerous far-field sites even higher [Dutton and Lambeck, 2012]. It has been suggested to generate this higher than present day sea level requires a retreat of both the Antarctic (AIS) and Greenland (GIS) Ice sheets beyond the present day extent, but the exact contribution of these two global ice sheets has yet to be resolved. By combing a Glacial Isostatic Adjustment (GIA) model with a suite of LIG ice-loading histories we will address a number of outstanding issues (i) What was the contribution of the AIS and GIS to ESL, (ii) Was the AIS or the GIS smaller during the LIG than the present interglacial? (iii) Can we generate the observed higher LIG RSL at a range of far-field sites? The suite of AIS and GIS ice-loading histories is constrained using the most recent near-field evidence, LIG stable isotope ice core data [Dahl-Jensen et al., 2013; Masson-Delmotte et al., 2011] and the output from ice sheet and climate models [Helsen et al., 2013; Pollard and DeConto, 2009; Stone et al., 2013]. Comparing the predicted RSL to a recent database of observed LIG far-field sea level [Dutton and Lambeck, 2012] allows for an assessment of the plausibility of the suite of ice loading histories. With this study, we aim to provide insight into the LIG history of the AIS and GIS. Dahl-Jensen, D., et al. (2013), Eemian interglacial reconstructed from a Greenland folded ice core, Nature, 493(7433), 489-494. Dutton, A., and K. Lambeck (2012), Ice Volume and Sea Level During the Last Interglacial, Science, 337(6091), 216-219. Helsen, M. M., W. J. van de Berg, R. S. W. van de Wal, M. R. van den Broeke, and J. Oerlemans (2013), Coupled regional climate-ice-sheet simulation shows limited Greenland ice loss during the Eemian, Clim Past, 9(4), 1773-1788. Masson-Delmotte, V., et al. (2011), A comparison of the present and last interglacial periods in six Antarctic ice cores, Clim Past, 7(2), 397-423. Pollard, D., and R. M. DeConto (2009), Modelling West Antarctic ice sheet growth and collapse through the past five million years, Nature, 458(7236), 329-U389. Stone, E. J., D. J. Lunt, J. D. Annan, and J. C. Hargreaves (2013), Quantification of the Greenland ice sheet contribution to Last Interglacial sea level rise, Clim Past, 9(2), 621-639.

Imprints of AMOC Perturbation in the Intermediate water of Equatorial Atlantic during the Last Interglacial Improved

NASA Astrophysics Data System (ADS)

Weldeab, S.

2014-12-01

Understanding of the last interglacial (LIG) is critical for the assessment of long-term impact of global warming on the Atlantic meridional overturning circulation (AMOC) and climate. Relative to the Millennium, air temperature over Greenland and eustatic sea-level during the LIG was higher by 8±4˚C and 4-8 m, with a considerable oscillation in the rate of meltwater input (NEEM Community rembers, Nature, v.493, p.489; Kopp et al., Nature, v. 462, p. 863) . The impact of millennial-scale LIG meltwater input on the AMOC and global climate is, however, less understood. Here we present a highly resolved, benthic foraminiferal multi-proxy record from the eastern equatorial Atlantic. The record shows that the LIG was punctuated by at least two episodes of reduced AMOC whose impact on the global climate varied considerably. While the event between 126,000 and 123,800 years ago lacks imprints on available global climate records, the AMOC perturbation between 129,000 and 128,000 years ago provides a causative link to a rapid increase of atmospheric CO2, peak air warming over Antarctica, and a slow down of the rate of global monsoon intensification. We suggest that the rate of meltwater input into the North Atlantic and the size of remanent Greenland ice sheet was critical in determining the degree of AMOC reduction and its effect on the interhemispheric climate.

A bacterial aromatic aldehyde dehydrogenase critical for the efficient catabolism of syringaldehyde.

PubMed

Kamimura, Naofumi; Goto, Takayuki; Takahashi, Kenji; Kasai, Daisuke; Otsuka, Yuichiro; Nakamura, Masaya; Katayama, Yoshihiro; Fukuda, Masao; Masai, Eiji

2017-03-15

Vanillin and syringaldehyde obtained from lignin are essential intermediates for the production of basic chemicals using microbial cell factories. However, in contrast to vanillin, the microbial conversion of syringaldehyde is poorly understood. Here, we identified an aromatic aldehyde dehydrogenase (ALDH) gene responsible for syringaldehyde catabolism from 20 putative ALDH genes of Sphingobium sp. strain SYK-6. All these genes were expressed in Escherichia coli, and nine gene products, including previously characterized BzaA, BzaB, and vanillin dehydrogenase (LigV), exhibited oxidation activities for syringaldehyde to produce syringate. Among these genes, SLG_28320 (desV) and ligV were most highly and constitutively transcribed in the SYK-6 cells. Disruption of desV in SYK-6 resulted in a significant reduction in growth on syringaldehyde and in syringaldehyde oxidation activity. Furthermore, a desV ligV double mutant almost completely lost its ability to grow on syringaldehyde. Purified DesV showed similar k cat /K m values for syringaldehyde (2100 s -1 ·mM -1 ) and vanillin (1700 s -1 ·mM -1 ), whereas LigV substantially preferred vanillin (8800 s -1 ·mM -1 ) over syringaldehyde (1.4 s -1 ·mM -1 ). These results clearly demonstrate that desV plays a major role in syringaldehyde catabolism. Phylogenetic analyses showed that DesV-like ALDHs formed a distinct phylogenetic cluster separated from the vanillin dehydrogenase cluster.

A bacterial aromatic aldehyde dehydrogenase critical for the efficient catabolism of syringaldehyde

PubMed Central

Kamimura, Naofumi; Goto, Takayuki; Takahashi, Kenji; Kasai, Daisuke; Otsuka, Yuichiro; Nakamura, Masaya; Katayama, Yoshihiro; Fukuda, Masao; Masai, Eiji

2017-01-01

Vanillin and syringaldehyde obtained from lignin are essential intermediates for the production of basic chemicals using microbial cell factories. However, in contrast to vanillin, the microbial conversion of syringaldehyde is poorly understood. Here, we identified an aromatic aldehyde dehydrogenase (ALDH) gene responsible for syringaldehyde catabolism from 20 putative ALDH genes of Sphingobium sp. strain SYK-6. All these genes were expressed in Escherichia coli, and nine gene products, including previously characterized BzaA, BzaB, and vanillin dehydrogenase (LigV), exhibited oxidation activities for syringaldehyde to produce syringate. Among these genes, SLG_28320 (desV) and ligV were most highly and constitutively transcribed in the SYK-6 cells. Disruption of desV in SYK-6 resulted in a significant reduction in growth on syringaldehyde and in syringaldehyde oxidation activity. Furthermore, a desV ligV double mutant almost completely lost its ability to grow on syringaldehyde. Purified DesV showed similar kcat/Km values for syringaldehyde (2100 s−1·mM−1) and vanillin (1700 s−1·mM−1), whereas LigV substantially preferred vanillin (8800 s−1·mM−1) over syringaldehyde (1.4 s−1·mM−1). These results clearly demonstrate that desV plays a major role in syringaldehyde catabolism. Phylogenetic analyses showed that DesV-like ALDHs formed a distinct phylogenetic cluster separated from the vanillin dehydrogenase cluster. PMID:28294121

Protective Immunity and Reduced Renal Colonization Induced by Vaccines Containing Recombinant Leptospira interrogans Outer Membrane Proteins and Flagellin Adjuvant

PubMed Central

Monaris, D.; Sbrogio-Almeida, M. E.; Dib, C. C.; Canhamero, T. A.; Souza, G. O.; Vasconcellos, S. A.; Ferreira, L. C. S.

2015-01-01

Leptospirosis is a global zoonotic disease caused by different Leptospira species, such as Leptospira interrogans, that colonize the renal tubules of wild and domestic animals. Thus far, attempts to develop effective leptospirosis vaccines, both for humans and animals, have failed to induce immune responses capable of conferring protection and simultaneously preventing renal colonization. In this study, we evaluated the protective immunity induced by subunit vaccines containing seven different recombinant Leptospira interrogans outer membrane proteins, including the carboxy-terminal portion of the immunoglobulinlike protein A (LigAC) and six novel antigens, combined with aluminum hydroxide (alum) or Salmonella flagellin (FliC) as adjuvants. Hamsters vaccinated with the different formulations elicited high antigen-specific antibody titers. Immunization with LigAC, either with alum or flagellin, conferred protective immunity but did not prevent renal colonization. Similarly, animals immunized with LigAC or LigAC coadministered with six leptospiral proteins with alum adjuvant conferred protection but did not reduce renal colonization. In contrast, immunizing animals with the pool of seven antigens in combination with flagellin conferred protection and significantly reduced renal colonization by the pathogen. The present study emphasizes the relevance of antigen composition and added adjuvant in the efficacy of antileptospirosis subunit vaccines and shows the complex relationship between immune responses and renal colonization by the pathogen. PMID:26108285

Does an early socialization into a food culture condition lifelong food preferences? Evidence from a retrospective study.

PubMed

Scrob, Mircea-Lucian

2016-06-01

The influence of early formed dietary practices on food choices and preferences during adulthood has often been assumed but rarely adequately demonstrated given the difficulty of studying the subject matter with conventional laboratory or observational research designs. This article examines this assumption by analyzing the information from 31 structured interviews on the respondents' current preferences for combinations of six side dishes with bread or mămăligă (boiled cornmeal mush, similar to polenta). All the respondents had consumed mămăligă in their childhood but in their adulthood had switched to bread following the social and economic upheavals from 1960s Romania. The results show that a) for specific combinations, physiological factors and/or cultural norms that defined bread as a 'prestigious' food have been capable of overriding the effects of early socialization with mămăligă as the accompanying food and b) that consumers continue to prefer certain side dishes with mămăligă even after decades of predominant consumption of bread although confounding factors might account for such preferences. These findings qualify the expectation that an early familiarization with healthy eating habits will promote this desired lifestyle during adulthood by showing that physiological and socio-cultural factors are capable of overriding its effects on hedonic preferences. Copyright © 2016 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Helmich, Kate E.; Pereira, Jose Henrique; Gall, Daniel L.

Here, lignin is a combinatorial polymer comprising monoaromatic units that are linked via covalent bonds. Although lignin is a potential source of valuable aromatic chemicals, its recalcitrance to chemical or biological digestion presents major obstacles to both the production of second-generation biofuels and the generation of valuable coproducts from lignin's monoaromatic units. Degradation of lignin has been relatively well characterized in fungi, but it is less well understood in bacteria. A catabolic pathway for the enzymatic breakdown of aromatic oligomers linked via β-aryl ether bonds typically found in lignin has been reported in the bacterium Sphingobium sp. SYK-6. Here, wemore » present x-ray crystal structures and biochemical characterization of the glutathione-dependent β-etherases, LigE and LigF, from this pathway. The crystal structures show that both enzymes belong to the canonical two-domain fold and glutathione binding site architecture of the glutathione S-transferase family. Mutagenesis of the conserved active site serine in both LigE and LigF shows that, whereas the enzymatic activity is reduced, this amino acid side chain is not absolutely essential for catalysis. The results include descriptions of cofactor binding sites, substrate binding sites, and catalytic mechanisms. Because β-aryl ether bonds account for 50–70% of all interunit linkages in lignin, understanding the mechanism of enzymatic β-aryl ether cleavage has significant potential for informing ongoing studies on the valorization of lignin.« less

Validation studies of the site-directed docking program LibDock.

PubMed

Rao, Shashidhar N; Head, Martha S; Kulkarni, Amit; LaLonde, Judith M

2007-01-01

The performance of the site-features docking algorithm LibDock has been evaluated across eight GlaxoSmithKline targets as a follow-up to a broad validation study of docking and scoring software (Warren, G. L.; Andrews, W. C.; Capelli, A.; Clarke, B.; Lalonde, J.; Lambert, M. H.; Lindvall, M.; Nevins, N.; Semus, S. F.; Senger, S.; Tedesco, G.; Walls, I. D.; Woolven, J. M.; Peishoff, C. E.; Head, M. S. J. Med. Chem. 2006, 49, 5912-5931). Docking experiments were performed to assess both the accuracy in reproducing the binding mode of the ligand and the retrieval of active compounds in a virtual screening protocol using both the DJD (Diller, D. J.; Merz, K. M., Jr. Proteins 2001, 43, 113-124) and LigScore2 (Krammer, A. K.; Kirchoff, P. D.; Jiang, X.; Venkatachalam, C. M.; Waldman, M. J. Mol. Graphics Modell. 2005, 23, 395-407) scoring functions. This study was conducted using DJD scoring, and poses were rescored using all available scoring functions in the Accelrys LigandFit module, including LigScore2. For six out of eight targets at least 30% of the ligands were docked within a root-mean-square difference (RMSD) of 2.0 A for the crystallographic poses when the LigScore2 scoring function was used. LibDock retrieved at least 20% of active compounds in the top 10% of screened ligands for four of the eight targets in the virtual screening protocol. In both studies the LigScore2 scoring function enhanced the retrieval of crystallographic poses or active compounds in comparison with the results obtained using the DJD scoring function. The results for LibDock accuracy and ligand retrieval in virtual screening are compared to 10 other docking and scoring programs. These studies demonstrate the utility of the LigScore2 scoring function and that LibDock as a feature directed docking method performs as well as docking programs that use genetic/growing and Monte Carlo driven algorithms.

Laser-induced porous graphene films from commercial polymers

NASA Astrophysics Data System (ADS)

Lin, Jian; Peng, Zhiwei; Liu, Yuanyue; Ruiz-Zepeda, Francisco; Ye, Ruquan; Samuel, Errol L. G.; Yacaman, Miguel Jose; Yakobson, Boris I.; Tour, James M.

2014-12-01

The cost effective synthesis and patterning of carbon nanomaterials is a challenge in electronic and energy storage devices. Here we report a one-step, scalable approach for producing and patterning porous graphene films with three-dimensional networks from commercial polymer films using a CO2 infrared laser. The sp3-carbon atoms are photothermally converted to sp2-carbon atoms by pulsed laser irradiation. The resulting laser-induced graphene (LIG) exhibits high electrical conductivity. The LIG can be readily patterned to interdigitated electrodes for in-plane microsupercapacitors with specific capacitances of >4 mF cm-2 and power densities of ~9 mW cm-2. Theoretical calculations partially suggest that enhanced capacitance may result from LIG’s unusual ultra-polycrystalline lattice of pentagon-heptagon structures. Combined with the advantage of one-step processing of LIG in air from commercial polymer sheets, which would allow the employment of a roll-to-roll manufacturing process, this technique provides a rapid route to polymer-written electronic and energy storage devices.

Altered kinetics of nonhomologous end joining and class switch recombination in ligase IV-deficient B cells.

PubMed

Han, Li; Yu, Kefei

2008-11-24

Immunoglobulin heavy chain class switch recombination (CSR) is believed to occur through the generation and repair of DNA double-strand breaks (DSBs) in the long and repetitive switch regions. Although implied, the role of the major vertebrate DSB repair pathway, nonhomologous end joining (NHEJ), in CSR has been controversial. By somatic gene targeting of DNA ligase IV (Lig4; a key component of NHEJ) in a B cell line (CH12F3) capable of highly efficient CSR in vitro, we found that NHEJ is required for efficient CSR. Disruption of the Lig4 gene in CH12F3 cells severely inhibits the initial rate of CSR and causes a late cell proliferation defect under cytokine stimulation. However, unlike V(D)J recombination, which absolutely requires NHEJ, CSR accumulates to a substantial level in Lig4-null cells. The data revealed a fast-acting NHEJ and a slow-acting alterative end joining of switch region breaks during CSR.

Separation of cordycepin from Cordyceps militaris fermentation supernatant using preparative HPLC and evaluation of its antibacterial activity as an NAD+-dependent DNA ligase inhibitor

PubMed Central

Zhou, Xiaofeng; Cai, Guoqiang; He, Yi; Tong, Guotong

2016-01-01

Cordycepin exhibits various bio-activities, including anticancer, antibacterial, antiviral and immune regulation activities, and is a significant focus of research. However, the preparation of high-purity cordycepin remains challenging. Also, the molecular target with which cordycepin interacts to cause an antibacterial effect remains unknown. In the present study, cordycepin was prepared by preparative high-performance liquid chromatography (prep-HPLC) and the purity obtained was 99.6%, indicating that this technique may be useful for the large-scale isolation of cordycepin in the future. The results of computational molecular docking analysis indicated that the interaction energy between cordycepin and NAD+-dependent DNA ligase (LigA) was lower than that between cordycepin and other common antibacterial targets. The highly pure cordycepin obtained by prep-HPLC demonstrated inhibitory activity against LigA from various bacteria in vitro. In conclusion, cordycepin may be useful as a broad-spectrum antibiotic targeting LigA in various bacteria. PMID:27588098

A novel transformation system using a bleomycin resistance marker with chemosensitizers for Aspergillus oryzae.

PubMed

Suzuki, Satoshi; Tada, Sawaki; Fukuoka, Mari; Taketani, Hiroko; Tsukakoshi, Yoshiki; Matsushita, Mayumi; Oda, Kosuke; Kusumoto, Ken-Ichi; Kashiwagi, Yutaka; Sugiyama, Masanori

2009-05-22

Aspergillus oryzae is resistant to many kinds of antibiotics, which hampers their use to select transformants. In fact, the fungus is resistant to over 200microg/ml of bleomycin (Bm). By enhancing the susceptibility of A. oryzae to Bm using Triton X-100 as a detergent and an ATP-binding cassette (ABC) pump inhibitor, chlorpromazine, to the growing medium, we established a novel transformation system by Bm selection for A. oryzae. In a medium containing these reagents, A. oryzae showed little growth even in the presence of 30microg Bm/ml. Based on these findings, we constructed a Bm-resistance expression cassette (BmR), in which blmB encoding Bm N-acetyltransferase from Bm-producing Streptomyces verticillus was expressed under the control of a fungal promoter. We obtained a gene knockout mutant efficiently by Bm selection, i.e., the chromosomal ligD coding region was successfully replaced by BmR using ligD disruption cassette consisted of ligD flanking sequence and BmR through homologous recombination.

Laser-induced porous graphene films from commercial polymers

PubMed Central

Lin, Jian; Peng, Zhiwei; Liu, Yuanyue; Ruiz-Zepeda, Francisco; Ye, Ruquan; Samuel, Errol L. G.; Yacaman, Miguel Jose; Yakobson, Boris I.; Tour, James M.

2014-01-01

Synthesis and patterning of carbon nanomaterials cost effectively is a challenge in electronic and energy storage devices. Here report a one-step, scalable approach for producing and patterning porous graphene films with 3-dimensional networks from commercial polymer films using a CO2 infrared laser. The sp3-carbon atoms are photothermally converted to sp2-carbon atoms by pulsed laser irradiation. The resulting laser-induced graphene (LIG) exhibits high electrical conductivity. The LIG can be readily patterned to interdigitated electrodes for in-plane microsupercapacitors with specific capacitances of >4 mF·cm−2 and power densities of ~9 mW·cm−2. Theoretical calculations partially suggest that enhanced capacitance may result from LIG’s unusual ultra-polycrystalline lattice of pentagon-heptagon structures. Combined with the advantage of one-step processing of LIG in air from commercial polymer sheets, which would allow the employment of a roll-to-roll manufacturing process, this technique provides a rapid route to polymer-written electronic and energy storage devices. PMID:25493446

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodriguez, Mark A.; Sava Gallis, Dorina F.; Chavez, James S.

We report here the synthesis of a neutral viologen derivative, C 24H 16N 2O 4·2H 2O. The non-solvent portion of the structure (Z-Lig) is a zwitterion, consisting of two positively charged pyridinium cations and two negatively charged carboxylate anions. The carboxylate group is almost coplanar [dihedral angle = 2.04 (11)°] with the benzene ring, whereas the dihedral angle between pyridine and benzene rings is 46.28 (5)°. TheZ-Lig molecule is positioned on a center of inversion (Fig. 1). The presence of the twofold axis perpendicular to thec-glide plane in space groupC2/c generates a screw-axis parallel to thebaxis that is shifted from themore » origin by 1/4 in theaandcdirections. This screw-axis replicates the molecule (and solvent water molecules) through space. TheZ-Lig molecule links to adjacent moleculesviaO—H...O hydrogen bonds involving solvent water molecules as well as intermolecular C—H...O interactions. There are also π–π interactions between benzene rings on adjacent molecules.« less

Structural basis of stereospecificity in the bacterial enzymatic cleavage of β-aryl ether bonds in lignin

DOE PAGES

Helmich, Kate E.; Pereira, Jose Henrique; Gall, Daniel L.; ...

2015-12-04

Here, lignin is a combinatorial polymer comprising monoaromatic units that are linked via covalent bonds. Although lignin is a potential source of valuable aromatic chemicals, its recalcitrance to chemical or biological digestion presents major obstacles to both the production of second-generation biofuels and the generation of valuable coproducts from lignin's monoaromatic units. Degradation of lignin has been relatively well characterized in fungi, but it is less well understood in bacteria. A catabolic pathway for the enzymatic breakdown of aromatic oligomers linked via β-aryl ether bonds typically found in lignin has been reported in the bacterium Sphingobium sp. SYK-6. Here, wemore » present x-ray crystal structures and biochemical characterization of the glutathione-dependent β-etherases, LigE and LigF, from this pathway. The crystal structures show that both enzymes belong to the canonical two-domain fold and glutathione binding site architecture of the glutathione S-transferase family. Mutagenesis of the conserved active site serine in both LigE and LigF shows that, whereas the enzymatic activity is reduced, this amino acid side chain is not absolutely essential for catalysis. The results include descriptions of cofactor binding sites, substrate binding sites, and catalytic mechanisms. Because β-aryl ether bonds account for 50–70% of all interunit linkages in lignin, understanding the mechanism of enzymatic β-aryl ether cleavage has significant potential for informing ongoing studies on the valorization of lignin.« less

Lysine 271 but not lysine 210 of XRCC4 is required for the nuclear localization of XRCC4 and DNA ligase IV

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fukuchi, Mikoto; Wanotayan, Rujira; Liu, Sicheng

2015-06-12

XRCC4 and DNA Ligase IV (LIG4) cooperate to join two DNA ends at the final step of DNA double-strand break (DSB) repair through non-homologous end-joining (NHEJ). However, it is not fully understood how these proteins are localized to the nucleus. Here we created XRCC4{sup K271R} mutant, as Lys271 lies within the putative nuclear localization signal (NLS), and XRCC4{sup K210R} mutant, as Lys210 was reported to undergo SUMOylation, implicated in the nuclear localization of XRCC4. Wild-type and mutated XRCC4 with EGFP tag were introduced into HeLa cell, in which endogenous XRCC4 had been knocked down using siRNA directed to 3′-untranslated region,more » and tested for the nuclear localization function by fluorescence microscopy. XRCC4{sup K271R} was defective in the nuclear localization of itself and LIG4, whereas XRCC4{sup K210R} was competent for the nuclear localization with LIG4. To examine DSB repair function, wild-type and mutated XRCC4 were introduced into XRCC4-deficient M10. M10-XRCC4{sup K271R}, but not M10-XRCC4{sup K210R}, showed significantly reduced surviving fraction after 2 Gy γ-ray irradiation as compared to M10-XRCC4{sup WT}. The number of γ-H2AX foci remaining 2 h after 2 Gy γ-ray irradiation was significantly greater in M10-XRCC4{sup K271R} than in M10-XRCC4{sup WT}, whereas it was only marginally increased in M10-XRCC4{sup K210R} as compared to M10-XRCC4{sup WT}. The present results collectively indicated that Lys271, but not Lys210, of XRCC4 is required for the nuclear localization of XRCC4 and LIG4 and that the nuclear localizing ability is essential for DSB repair function of XRCC4. - Highlights: • XRCC4{sup K271R} is defective in the nuclear localization of itself and LIG4. • XRCC4{sup K210R} is competent for the nuclear localization of itself and LIG4. • XRCC4{sup K271R} is deficient in DSB repair function. • XRCC4{sup K210R} is mostly normal in DSB repair function.« less

Molecular Dynamic Studies of the Complex Polyethylenimine and Glucose Oxidase.

PubMed

Szefler, Beata; Diudea, Mircea V; Putz, Mihai V; Grudzinski, Ireneusz P

2016-10-27

Glucose oxidase (GOx) is an enzyme produced by Aspergillus, Penicillium and other fungi species. It catalyzes the oxidation of β-d-glucose (by the molecular oxygen or other molecules, like quinones, in a higher oxidation state) to form d-glucono-1,5-lactone, which hydrolyses spontaneously to produce gluconic acid. A coproduct of this enzymatic reaction is hydrogen peroxide (H₂O₂). GOx has found several commercial applications in chemical and pharmaceutical industries including novel biosensors that use the immobilized enzyme on different nanomaterials and/or polymers such as polyethylenimine (PEI). The problem of GOx immobilization on PEI is retaining the enzyme native activity despite its immobilization onto the polymer surface. Therefore, the molecular dynamic (MD) study of the PEI ligand (C14N8_07_B22) and the GOx enzyme (3QVR) was performed to examine the final complex PEI-GOx stabilization and the affinity of the PEI ligand to the docking sites of the GOx enzyme. The docking procedure showed two places/regions of major interaction of the protein with the polymer PEI: (LIG1) of -5.8 kcal/mol and (LIG2) of -4.5 kcal/mol located inside the enzyme and on its surface, respectively. The values of enthalpy for the PEI-enzyme complex, located inside of the protein (LIG1) and on its surface (LIG2) were computed. Docking also discovered domains of the GOx protein that exhibit no interactions with the ligand or have even repulsive characteristics. The structural data clearly indicate some differences in the ligand PEI behavior bound at the two places/regions of glucose oxidase.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wong, Fuh Yong, E-mail: fuhyong@yahoo.com; Wang, Fuqiang; Chen, John Ju

Purpose: To examine the outcomes of Southeast Asian (SEA) women with low-risk ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS) and adjuvant radiation therapy. Methods and Materials: Retrospective chart reviews of patients treated with BCS for DCIS from 1995 to 2011 were performed. Patients meeting the selection criteria from Eastern Cooperative Oncology Group 5194 were included. Most patients received adjuvant radiation therapy (RT) consisting of whole-breast RT delivered to 50 Gy followed by a 10-Gy boost to the tumor bed. Results: Of 744 patients with pathologic diagnosis of pure DCIS identified, 273 met the selection criteria: low-intermediate grade (LIG),more » n=219; high grade (HG), n=54. Median follow-up for these patients was 60 months. There were 8 ipsilateral breast tumor recurrences (IBTRs) in total, 7 of which were DCIS. The estimated actuarial IBTR rates at 5 and 10 years for the entire cohort are 1.8% and 4.3%, respectively. Of the 219 patients with LIG DCIS, 210 received RT and 9 did not. There were 7 IBTRs in LIG DCIS, 2 among the 9 patients who did not receive RT. The IBTR rates in LIG DCIS at 5 and 10 years are 2.3% and 4.2%, respectively. All patients with HG DCIS received RT. There was only 1 IBTR occurring beyond 5 years, giving an estimated IBTR rate of 4.5% at 10 years. Conclusions: SEA women with screen-detected DCIS have exceedingly low rates of IBTR after BCS, comparable to that observed in reports of similar patients with low-risk DCIS treated with adjuvant radiation.« less

The role of host DNA ligases in hepadnavirus covalently closed circular DNA formation

PubMed Central

Long, Quanxin; Yan, Ran; Hu, Jieli; Cai, Dawei; Kim, Elena S.; Zhang, Hu; Liu, Yuanjie

2017-01-01

Hepadnavirus covalently closed circular (ccc) DNA is the bona fide viral transcription template, which plays a pivotal role in viral infection and persistence. Upon infection, the non-replicative cccDNA is converted from the incoming and de novo synthesized viral genomic relaxed circular (rc) DNA, presumably through employment of the host cell’s DNA repair mechanisms in the nucleus. The conversion of rcDNA into cccDNA requires preparation of the extremities at the nick/gap regions of rcDNA for strand ligation. After screening 107 cellular DNA repair genes, we herein report that the cellular DNA ligase (LIG) 1 and 3 play a critical role in cccDNA formation. Ligase inhibitors or functional knock down/out of LIG1/3 significantly reduced cccDNA production in an in vitro cccDNA formation assay, and in cccDNA-producing cells without direct effect on viral core DNA replication. In addition, transcomplementation of LIG1/3 in the corresponding knock-out or knock-down cells was able to restore cccDNA formation. Furthermore, LIG4, a component in non-homologous end joining DNA repair apparatus, was found to be responsible for cccDNA formation from the viral double stranded linear (dsl) DNA, but not rcDNA. In conclusion, we demonstrate that hepadnaviruses utilize the whole spectrum of host DNA ligases for cccDNA formation, which sheds light on a coherent molecular pathway of cccDNA biosynthesis, as well as the development of novel antiviral strategies for treatment of hepatitis B. PMID:29287110

Upgrade to Ion Exchange Modeling for Removal of Technetium from Hanford Waste Using SuperLig® 639 Resin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamm, L.; Smith, F.; Aleman, S.

2013-05-16

This report documents the development and application of computer models to describe the sorption of pertechnetate [TcO₄⁻], and its surrogate perrhenate [ReO₄⁻], on SuperLig® 639 resin. Two models have been developed: 1) A thermodynamic isotherm model, based on experimental data, that predicts [TcO₄⁻] and [ReO₄⁻] sorption as a function of solution composition and temperature and 2) A column model that uses the isotherm calculated by the first model to simulate the performance of a full-scale sorption process. The isotherm model provides a synthesis of experimental data collected from many different sources to give a best estimate prediction of the behaviormore » of the pertechnetate-SuperLig® 639 system and an estimate of the uncertainty in this prediction. The column model provides a prediction of the expected performance of the plant process by determining the volume of waste solution that can be processed based on process design parameters such as column size, flow rate and resin physical properties.« less

Predicting Ligand Binding Sites on Protein Surfaces by 3-Dimensional Probability Density Distributions of Interacting Atoms

PubMed Central

Jian, Jhih-Wei; Elumalai, Pavadai; Pitti, Thejkiran; Wu, Chih Yuan; Tsai, Keng-Chang; Chang, Jeng-Yih; Peng, Hung-Pin; Yang, An-Suei

2016-01-01

Predicting ligand binding sites (LBSs) on protein structures, which are obtained either from experimental or computational methods, is a useful first step in functional annotation or structure-based drug design for the protein structures. In this work, the structure-based machine learning algorithm ISMBLab-LIG was developed to predict LBSs on protein surfaces with input attributes derived from the three-dimensional probability density maps of interacting atoms, which were reconstructed on the query protein surfaces and were relatively insensitive to local conformational variations of the tentative ligand binding sites. The prediction accuracy of the ISMBLab-LIG predictors is comparable to that of the best LBS predictors benchmarked on several well-established testing datasets. More importantly, the ISMBLab-LIG algorithm has substantial tolerance to the prediction uncertainties of computationally derived protein structure models. As such, the method is particularly useful for predicting LBSs not only on experimental protein structures without known LBS templates in the database but also on computationally predicted model protein structures with structural uncertainties in the tentative ligand binding sites. PMID:27513851

Preliminary study of semi-refined carrageenan (SRC) as secondary gelling agent in natural rubber (NR) latex foam

NASA Astrophysics Data System (ADS)

Norhazariah, S.; Azura, A. R.; Azahari, B.; Sivakumar, R.

2017-12-01

Semi-refined carrageenan (SRC) product is considerably cheaper and easier to produce as a natural polysaccharide, which was utilized in food and other product application. However, the application in latex is limited. The aim of this work is to evaluate the SRC produced from low industrial grade seaweed (LIGS) in the latex foam application. The FTIR spectra showed the SRC produced as kappa type carrageenan with lower sulfur content compared to native LIGS. NR latex foam is produced by using the Dunlop method with some modifications. The effect of SRC loading as a secondary gelling agent in NR latex foam is investigated. The density and morphology of the NR latex foam with the addition of the SRC are analyzed. NR latex foam density increased with SRC loading and peaked at 1.8 phr SRC. The addition of SRC has induced the bigger cell size compared to the cell size of the control NR latex foam, as shown in the optical micrograph. It can be concluded that SRC LIGS could be acted as secondary gelling agent in NR latex foam.

4,4'-([4,4'-Bipyridine]-1,1'-diium-1,1'-diyl)dibenzoate dihydrate

DOE PAGES

Rodriguez, Mark A.; Sava Gallis, Dorina F.; Chavez, James S.; ...

2016-06-01

We report here the synthesis of a neutral viologen derivative, C 24H 16N 2O 4·2H 2O. The non-solvent portion of the structure (Z-Lig) is a zwitterion, consisting of two positively charged pyridinium cations and two negatively charged carboxylate anions. The carboxylate group is almost coplanar [dihedral angle = 2.04 (11)°] with the benzene ring, whereas the dihedral angle between pyridine and benzene rings is 46.28 (5)°. TheZ-Lig molecule is positioned on a center of inversion (Fig. 1). The presence of the twofold axis perpendicular to thec-glide plane in space groupC2/c generates a screw-axis parallel to thebaxis that is shifted from themore » origin by 1/4 in theaandcdirections. This screw-axis replicates the molecule (and solvent water molecules) through space. TheZ-Lig molecule links to adjacent moleculesviaO—H...O hydrogen bonds involving solvent water molecules as well as intermolecular C—H...O interactions. There are also π–π interactions between benzene rings on adjacent molecules.« less

Anterior cruciate ligament reconstruction with a novel porcine xenograft: the initial Italian experience

PubMed Central

ZAFFAGNINI, STEFANO; GRASSI, ALBERTO; MUCCIOLI, GIULIO MARIA MARCHEGGIANI; DI SARSINA, TOMMASO ROBERTI; RAGGI, FEDERICO; BENZI, ANDREA; MARCACCI, MAURILIO

2015-01-01

At the current state of the art in anterior cruciate ligament (ACL) reconstruction, multiple techniques have been presented but none has given clearly defined and improved results. One of the main issues concerns the choice of graft. The concept of using xenograft tissue, defined as a graft tissue from one species and destined for implantation in an unlike species, was introduced in order to try to overcome the mechanical and biological concerns associated with synthetic materials and the safety and quality concerns and availability problems of allograft tissue. Xenograft tissue carries the risk of producing an immunological reaction. In order to try to overcome or attenuate the immune response against porcine xenograft tissue, the Z-Process® (Aperion Biologics Inc, San Antonio, Texas, USA) has been developed and used to produce the Z-Lig® family of devices for ACL reconstruction procedures. Z-Lig® is a tendon graft with or without bone blocks, sourced from animal tissue in a manner consistent with what has normally been sourced from human tissue, and processed to overcome anti-Gal-mediated rejection and to attenuate other immunological recognition in humans. All this while ensuring sterility, viral inactivation and preservation of mechanical proprieties appropriate for an ACL reconstruction device. The Z-Lig® device has been tested in skeletally mature monkeys and given interesting and promising results from the preclinical performance and safety profile point of view. On this basis, it was possible to proceed with the first clinical trial involving humans, which gave similar encouraging results. The Z-Lig® device has also been implanted in Italy at the Rizzoli Orthopaedic Institute in Bologna, as a part of international multicenter prospective randomized blinded controlled study aimed at comparing xenograft with allograft tissue. PMID:26605257

Effect of number of pig embryos in the uterus on their survival and development and on maternal metabolism.

PubMed

Père, M C; Dourmad, J Y; Etienne, M

1997-05-01

The effects of pig embryo number on fetal survival and growth and maternal metabolism were evaluated with 114 Large White gilts. Gilts were assigned at 38 kg to three treatments: control (CTR), ligature of the left oviduct (LIG), or right hemi-hysteroovariectomy (HHO). Insemination occurred at 311 +/- 18 d of age. A laparotomy was performed at d 35 of gestation, and gilts were slaughtered at d 112. Ovulation rate per uterine horn was 4.30, 8.70, and 17.12 in the LIG, CTR, and HHO groups, respectively. The hierarchy was the same for litter size at d 35 of gestation, but the relative differences were reduced (3.24, 5.98, and 8.40 fetuses/uterine horn, respectively). Litter size per uterine horn was similar in the CTR and HHO groups at d 112 of pregnancy (2.93, 4.69, and 4.76 fetuses in the LIG, CTR, and HHO groups, respectively). Early (before d 35 of gestation), late, and total fetal mortality increased with embryo potential per uterine horn. There was a compensation between early and late fetal mortality in the CTR and HHO groups. Fetal weight at d 112 was related to litter size in early pregnancy (1.50, 1.38, and 1.27 kg in the LIG, CTR, and HHO groups, respectively). Uterine capacity limits litter size and fetal development, even in sows with a conventional potential of embryos. Availability of energetic and gluconeogenic substrates was higher at 110 than at 60 d of gestation in the three groups. Blood substrate levels suggested that lipid mobilization and glucose uptake were higher in the gilts with a larger litter weight.

Molecular data and ecological niche modelling reveal the Pleistocene history of a semi-aquatic bug (Microvelia douglasi douglasi) in East Asia.

PubMed

Ye, Zhen; Zhu, Gengping; Chen, Pingping; Zhang, Danli; Bu, Wenjun

2014-06-01

This study investigated the Pleistocene history of a semi-aquatic bug, Microvelia douglasi douglasi Scott, 1874 (Hemiptera: Veliidae) in East Asia. We used M. douglasi douglasi as a model species to explore the effects of historical climatic fluctuations on montane semi-aquatic invertebrate species. Two hypotheses were developed using ecological niche models (ENMs). First, we hypothesized that M. douglasi douglasi persisted in suitable habitats in southern Guizhou, southern Yunnan, Hainan, Taiwan and southeast China during the LIG. After that, the populations expanded (Hypothesis 1). As the spatial prediction in the LGM was significantly larger than in the LIG, we then hypothesized that the population expanded during the LIG to LGM transition (Hypothesis 2). We tested these hypotheses using mitochondrial data (COI+COII) and nuclear data (ITS1+5.8S+ITS2). Young lineages, relatively deep splits, lineage differentiation among mountain ranges in central, south and southwest China and high genetic diversities were observed in these suitable habitats. Evidence of mismatch distributions and neutrality tests indicate that a population expansion occurred in the late Pleistocene. The Bayesian skyline plot (BSP) revealed an unusual population expansion that likely happened during the cooling transition between LIG and LGM. The results of genetic data were mostly consistent with the spatial predictions from ENM, a finding that can profoundly improve phylogeographic research. The ecological requirements of M. douglasi douglasi, together with the geographical heterogeneity and climatic fluctuations of Pleistocene in East Asia, could have shaped this unusual demographic history. Our study contributes to our knowledge of semi-aquatic bug/invertebrate responses to Pleistocene climatic fluctuations in East Asia. © 2014 John Wiley & Sons Ltd.

Polymorphisms of LIG4, BTBD2, HMGA2, and RTEL1 Genes Involved in the Double-Strand Break Repair Pathway Predict Glioblastoma Survival

PubMed Central

Liu, Yanhong; Shete, Sanjay; Etzel, Carol J.; Scheurer, Michael; Alexiou, George; Armstrong, Georgina; Tsavachidis, Spyros; Liang, Fu-Wen; Gilbert, Mark; Aldape, Ken; Armstrong, Terri; Houlston, Richard; Hosking, Fay; Robertson, Lindsay; Xiao, Yuanyuan; Wiencke, John; Wrensch, Margaret; Andersson, Ulrika; Melin, Beatrice S.; Bondy, Melissa

2010-01-01

Purpose Glioblastoma (GBM) is the most common and aggressive type of glioma and has the poorest survival. However, a small percentage of patients with GBM survive well beyond the established median. Therefore, identifying the genetic variants that influence this small number of unusually long-term survivors may provide important insight into tumor biology and treatment. Patients and Methods Among 590 patients with primary GBM, we evaluated associations of survival with the 100 top-ranking glioma susceptibility single nucleotide polymorphisms from our previous genome-wide association study using Cox regression models. We also compared differences in genetic variation between short-term survivors (STS; ≤ 12 months) and long-term survivors (LTS; ≥ 36 months), and explored classification and regression tree analysis for survival data. We tested results using two independent series totaling 543 GBMs. Results We identified LIG4 rs7325927 and BTBD2 rs11670188 as predictors of STS in GBM and CCDC26 rs10464870 and rs891835, HMGA2 rs1563834, and RTEL1 rs2297440 as predictors of LTS. Further survival tree analysis revealed that patients ≥ 50 years old with LIG4 rs7325927 (V) had the worst survival (median survival time, 1.2 years) and exhibited the highest risk of death (hazard ratio, 17.53; 95% CI, 4.27 to 71.97) compared with younger patients with combined RTEL1 rs2297440 (V) and HMGA2 rs1563834 (V) genotypes (median survival time, 7.8 years). Conclusion Polymorphisms in the LIG4, BTBD2, HMGA2, and RTEL1 genes, which are involved in the double-strand break repair pathway, are associated with GBM survival. PMID:20368557

Polymorphisms of LIG4, BTBD2, HMGA2, and RTEL1 genes involved in the double-strand break repair pathway predict glioblastoma survival.

PubMed

Liu, Yanhong; Shete, Sanjay; Etzel, Carol J; Scheurer, Michael; Alexiou, George; Armstrong, Georgina; Tsavachidis, Spyros; Liang, Fu-Wen; Gilbert, Mark; Aldape, Ken; Armstrong, Terri; Houlston, Richard; Hosking, Fay; Robertson, Lindsay; Xiao, Yuanyuan; Wiencke, John; Wrensch, Margaret; Andersson, Ulrika; Melin, Beatrice S; Bondy, Melissa

2010-05-10

Glioblastoma (GBM) is the most common and aggressive type of glioma and has the poorest survival. However, a small percentage of patients with GBM survive well beyond the established median. Therefore, identifying the genetic variants that influence this small number of unusually long-term survivors may provide important insight into tumor biology and treatment. Among 590 patients with primary GBM, we evaluated associations of survival with the 100 top-ranking glioma susceptibility single nucleotide polymorphisms from our previous genome-wide association study using Cox regression models. We also compared differences in genetic variation between short-term survivors (STS; or= 36 months), and explored classification and regression tree analysis for survival data. We tested results using two independent series totaling 543 GBMs. We identified LIG4 rs7325927 and BTBD2 rs11670188 as predictors of STS in GBM and CCDC26 rs10464870 and rs891835, HMGA2 rs1563834, and RTEL1 rs2297440 as predictors of LTS. Further survival tree analysis revealed that patients >or= 50 years old with LIG4 rs7325927 (V) had the worst survival (median survival time, 1.2 years) and exhibited the highest risk of death (hazard ratio, 17.53; 95% CI, 4.27 to 71.97) compared with younger patients with combined RTEL1 rs2297440 (V) and HMGA2 rs1563834 (V) genotypes (median survival time, 7.8 years). Polymorphisms in the LIG4, BTBD2, HMGA2, and RTEL1 genes, which are involved in the double-strand break repair pathway, are associated with GBM survival.

Sea-level history and tectonic uplift during the last-interglacial period (LIG): Inferred from the Bab al-Mandab coral reef terraces, southern Red Sea

NASA Astrophysics Data System (ADS)

Al-Mikhlafi, Ahmed Saif; Edwards, Lawrence R.; Cheng, Hai

2018-02-01

Results of U-series dating of late Pleistocene raised coral reef terraces from the Bab al-Mandab area, define two distinct groups: (1) well-preserved aragonitic fossil corals recorded from the Al-Hajaja terrace (Tr3) yield ages for last-interglacial period (LIG); and (2) calcitic fossil corals recovered from Perim Island terrace (Tr1) show varying degrees of U-series open system behavior and yield coral assemblage ages of LIG and older ages. Fossil corals from Tr1 are recrystallized corals, have anomalously high initial δ234U ranged from (152 ± 2‰ to 287 ± 7‰), corresponding to ages of ∼120 ka and ∼406 ka, respectively. Applying age reliability criteria on the current data suggest majority of the ages cannot be considered reliable and all are suspected for open system behavior associated with U loss/addition that significantly affects the 230Th/U ages. The diagenesis shown by these corals occurred probably due to extensive interaction of fossil corals with freshwater during the wet periods prevailed in southern Arabia coeval with the African monsoon, which led to U loss. Post-depositional U loss suggest (230Th/238U) increase, which shift the U-Th ages to unexpectedly higher levels as it is shown here. Measured elevation at the Al-Hajaja terrace (Tr3) is ∼4 ± 2 m above present sea level (apsl) consistent with eustatic sea level changes and indicates that the Bab al-Mandab area is stable at least since the LIG period. The Perim Island terrace (Tr1) is at elevation of 7 ± 2 m apsl; its reef yields diageneticaly-altered corals of multiple ages and cannot be used for sea level reconstructions.

NIST-NRC Comparison of Total Immersion Liquid-in-Glass Thermometers

NASA Astrophysics Data System (ADS)

Hill, K. D.; Gee, D. J.; Cross, C. D.; Strouse, G. F.

2009-02-01

The use of liquid-in-glass (LIG) thermometers is described in many documentary standards in the fields of environmental testing, material testing, and material transfer. Many national metrology institutes, including the National Institute of Standards and Technology (NIST) and the National Research Council of Canada (NRC), list calibration services for these thermometers among the Calibration Measurement Capabilities of Appendix C of the BIPM Key Comparison Database. NIST and NRC arranged a bilateral comparison of a set of total-immersion ASTM-type LIG thermometers to validate their uncertainty claims. Two each of ASTM thermometer types 62C through 69C were calibrated at NIST and at NRC at four temperatures distributed over the range appropriate to each thermometer, in addition to the ice point. Collectively, the thermometers span a temperature range of - 38 °C to 305 °C. In total, 160 measurements (80 pairs) comprise the comparison data set. Pair-wise differences ( T NIST- T NRC) were formed for each thermometer at each temperature. For 8 of the 80 pairs (10 %), the differences exceed the k = 2 combined uncertainties. These results support the claimed capabilities of NIST and NRC for the calibration of LIG thermometers.

Anti-infectious drug repurposing using an integrated chemical genomics and structural systems biology approach.

PubMed

Ng, Clara; Hauptman, Ruth; Zhang, Yinliang; Bourne, Philip E; Xie, Lei

2014-01-01

The emergence of multi-drug and extensive drug resistance of microbes to antibiotics poses a great threat to human health. Although drug repurposing is a promising solution for accelerating the drug development process, its application to anti-infectious drug discovery is limited by the scope of existing phenotype-, ligand-, or target-based methods. In this paper we introduce a new computational strategy to determine the genome-wide molecular targets of bioactive compounds in both human and bacterial genomes. Our method is based on the use of a novel algorithm, ligand Enrichment of Network Topological Similarity (ligENTS), to map the chemical universe to its global pharmacological space. ligENTS outperforms the state-of-the-art algorithms in identifying novel drug-target relationships. Furthermore, we integrate ligENTS with our structural systems biology platform to identify drug repurposing opportunities via target similarity profiling. Using this integrated strategy, we have identified novel P. falciparum targets of drug-like active compounds from the Malaria Box, and suggest that a number of approved drugs may be active against malaria. This study demonstrates the potential of an integrative chemical genomics and structural systems biology approach to drug repurposing.

EMP-1 is a junctional protein in a liver stem cell line and in the liver.

PubMed

Lee, Hsuan-Shu; Sherley, James L; Chen, Jeremy J W; Chiu, Chien-Chang; Chiou, Ling-Ling; Liang, Ja-Der; Yang, Pan-Chyr; Huang, Guan-Tarn; Sheu, Jin-Chuan

2005-09-09

In an attempt to discover cell markers for liver stem cells, a cDNA microarray analysis was carried out to compare the gene expression profiles between an adult liver stem cell line, Lig-8, and mature hepatocytes. Several genes in the categories of extracellular matrix, cell membrane, cell adhesion, transcription factor, signal molecule, transporter, and metabolic enzyme were shown to be differentially expressed in Lig-8 cells. Among them, epithelial membrane protein (EMP)-1 has been previously implicated with stem cell phenotypes. Antiserum to EMP-1 was produced to localize its expression. On monolayers of Lig-8 cells, EMP-1 was expressed along the intercellular border. In the liver harboring proliferating oval cells, the liver progenitors, EMP-1 was localized as ribbon bands, a staining pattern for epithelial junctions, all the way through bile duct epithelia, oval cell ductules, and into peri-hepatocytic regions. These peri-hepatocytic regions were proved to be bile canaliculi by co-localization of EMP-1 and dipeptidyl peptidase IV, an enzyme located on bile canaliculi. This report is the first to indicate EMP-1 to be a junctional protein in the liver.

Methylation of DNA Ligase 1 by G9a/GLP Recruits UHRF1 to Replicating DNA and Regulates DNA Methylation.

PubMed

Ferry, Laure; Fournier, Alexandra; Tsusaka, Takeshi; Adelmant, Guillaume; Shimazu, Tadahiro; Matano, Shohei; Kirsh, Olivier; Amouroux, Rachel; Dohmae, Naoshi; Suzuki, Takehiro; Filion, Guillaume J; Deng, Wen; de Dieuleveult, Maud; Fritsch, Lauriane; Kudithipudi, Srikanth; Jeltsch, Albert; Leonhardt, Heinrich; Hajkova, Petra; Marto, Jarrod A; Arita, Kyohei; Shinkai, Yoichi; Defossez, Pierre-Antoine

2017-08-17

DNA methylation is an essential epigenetic mark in mammals that has to be re-established after each round of DNA replication. The protein UHRF1 is essential for this process; it has been proposed that the protein targets newly replicated DNA by cooperatively binding hemi-methylated DNA and H3K9me2/3, but this model leaves a number of questions unanswered. Here, we present evidence for a direct recruitment of UHRF1 by the replication machinery via DNA ligase 1 (LIG1). A histone H3K9-like mimic within LIG1 is methylated by G9a and GLP and, compared with H3K9me2/3, more avidly binds UHRF1. Interaction with methylated LIG1 promotes the recruitment of UHRF1 to DNA replication sites and is required for DNA methylation maintenance. These results further elucidate the function of UHRF1, identify a non-histone target of G9a and GLP, and provide an example of a histone mimic that coordinates DNA replication and DNA methylation maintenance. Copyright © 2017 Elsevier Inc. All rights reserved.

Eemian and Holocene interglacial climate in northwest Greenland inferred from insect assemblages, lipid δ2H, and chitin δ18O preserved in lake sediments

NASA Astrophysics Data System (ADS)

McFarlin, J. M.; Axford, Y.; Osburn, M. R.; Lasher, G. E.; Kelly, M. A.; Osterberg, E. C.; Francis, D. R.; Farnsworth, L. B.

2016-12-01

We present a millennial-scale reconstruction of Holocene and Last Interglacial (Eemian) climate in northwest Greenland, inferred from insect assemblages (chironomid-inferred temperatures, CITs) and compound-specific organic isotopes (sedimentary lipid δ2H and chitin δ18O). Sediment cores collected from `Wax Lips Lake' (informal name), a non-glacial lake situated <2 km from the present margin of the Greenland Ice Sheet, yield radiocarbon ages that indicate preservation of Holocene lake sediments as well as an underlying unit of interglacial lake sediments that predate the Last Glacial Maximum (LGM). Terrestrial archives of continuous interglacial climate that predate the LGM and capture peak Last Interglacial (LIG) warmth are rare in Greenland and across the glaciated Arctic. Our quantitative estimates of LIG temperatures are derived from CITs and supported by enrichment in stable isotopes of precipitation (in both lipid δ2H and chitin δ18O) and the presence of the warm-dwelling insect Chaoboridae. Our record agrees with estimates of the peak LIG temperature anomaly (relative to the last millennium) from ice cores at NEEM (+8±4°C; Dahl-Jensen et al. 2013), also in northern Greenland. Peak LIG temperatures at both sites exceeded those of the Holocene. We pair an independent temperature proxy with proxies recording the stable isotopic composition of precipitation and lake water at this high-latitude site to provide insight on how hydroclimate changed over Arctic Greenland during two different warm periods - the Holocene Thermal Maximum and the LIG. We find general agreement amongst recorders of lake water isotopic composition, including δ18O of chitin from chironomid head capsules and δ2H of aquatic lipids. We infer the isotopic composition of precipitation from δ2H of long-chain n-alkanes from terrestrial plants. The δ2H of long-chain n-alkanes are internally consistent and deviate from lake water during prolonged periods of warmth, indicating changes in precipitation source, effective moisture, and/or seasonality associated with warming. We also briefly discuss our ongoing work to further characterize the source, distribution and isotopic composition of modern plant lipids in Greenlandic lakes, and thus clarify potential controls on past shifts recorded in sedimentary records.

Thermal comfort analysis: A case study of LIG housing in Chhattisgarh

NASA Astrophysics Data System (ADS)

Netam, Nisha; Sanyal, Shubhashis; Bhowmick, Shubhankar

2016-07-01

The present work reports the evaluation of temperature distribution inside a Low Income Group (LIG) house located in the city of Raipur, Chhattisgarh, using a Agros2D which is multi-platform C++ application capable of higher-order finite element formulation with h, p and hp adaptivity for the solution of differential equations based on the Hermes library. Variation of room air temperature along the length (x) of the house is calculated at different altitudes viz. 0.5m, 1m, 1.5m, 2m, 2.5m, and 3m. 2D model is generated for all the respective altitudes which show the temperature distribution inside the building.

Ion Exchange Column Tests Supporting Technetium Removal Resin Maturation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nash, C.; McCabe, D.; Hamm, L.

2013-12-20

The primary treatment of the tank waste at the DOE Hanford site will be done in the Waste Treatment and Immobilization Plant, currently under construction. The baseline plan for this facility is to treat the waste, splitting it into High Level Waste (HLW) and Low Activity Waste (LAW). Both waste streams are then separately vitrified as glass and sealed in canisters. The LAW glass will be disposed on site. There are currently no plans to treat the waste to remove technetium, so its disposition path is the LAW glass. Due to the soluble properties of pertechnetate and long half-life ofmore » 99Tc, effective management of 99Tc is important. Options are being explored to immobilize the supplemental LAW portion of the tank waste, as well as to examine the volatility of 99Tc during the vitrification process. Removal of 99Tc, followed by off-site disposal has potential to reduce treatment and disposal costs. A conceptual flow sheets for supplemental LAW treatment and disposal that could benefit from technetium removal will specifically examine removing 99Tc from the LAW feed stream to supplemental immobilization. SuperLig® 639 is an elutable ion exchange resin. In the tank waste, 99Tc is predominantly found in the tank supernate as pertechnetate (TcO 4 -). Perrhenate (ReO 4 -) has been shown to be a good non-radioactive surrogate for pertechnetate in laboratory testing for this ion exchange resin. This report contains results of experimental ion exchange distribution coefficient and column resin maturation kinetics testing using the resin SuperLig® 639a to selectively remove perrhenate from simulated LAW. This revision includes results from testing to determine effective resin operating temperature range. Loading tests were performed at 45°C, and the computer modeling was updated to include the temperature effects. Equilibrium contact testing indicated that this batch of SuperLig® 639 resin has good performance, with an average perrhenate distribution coefficient of 291 mL/g at a 100:1 phase ratio. This slightly exceeds the computer-modeled equilibrium distribution. The modeling agreed well with the experimental data for perrhenate removal with minor adjustments. Predicted breakthrough performance was on average within about 20% of measured values.« less

Development of Transcriptional Fusions to Assess Leptospira interrogans Promoter Activity

PubMed Central

Cerqueira, Gustavo M.; Souza, Natalie M.; Araújo, Eduardo R.; Barros, Aline T.; Morais, Zenaide M.; Vasconcellos, Sílvio A.; Nascimento, Ana L. T. O.

2011-01-01

Background Leptospirosis is a zoonotic infectious disease that affects both humans and animals. The existing genetic tools for Leptospira spp. have improved our understanding of the biology of this spirochete as well as the interaction of pathogenic leptospires with the mammalian host. However, new tools are necessary to provide novel and useful information to the field. Methodology and Principal Findings A series of promoter-probe vectors carrying a reporter gene encoding green fluorescent protein (GFP) were constructed for use in L. biflexa. They were tested by constructing transcriptional fusions between the lipL41, Leptospiral Immunoglobulin-like A (ligA) and Sphingomielynase 2 (sph2) promoters from L. interrogans and the reporter gene. ligA and sph2 promoters were the most active, in comparison to the lipL41 promoter and the non-induced controls. The results obtained are in agreement with LigA expression from the L. interrogans Fiocruz L1-130 strain. Conclusions The novel vectors facilitated the in vitro evaluation of L. interrogans promoter activity under defined growth conditions which simulate the mammalian host environment. The fluorescence and rt-PCR data obtained closely reflected transcriptional regulation of the promoters, thus demonstrating the suitability of these vectors for assessing promoter activity in L. biflexa. PMID:21445252

Development of transmucosal patch loaded with anesthetic and analgesic for dental procedures and in vivo evaluation.

PubMed

Nidhi, Malviya; Patro, M Nagaraju; Kusumvalli, Somisetty; Kusumdevi, Vemula

2016-01-01

Most of the dental surgeries require preoperative anesthetic and postoperative analgesic for painless procedures. A multidrug transmucosal drug delivery system loaded with lignocaine (Lig) base for immediate release and solid lipid nanoparticles (SLNs) of diclofenac (Dic) diethylamine for prolonged release was developed. SLNs were prepared by solvent emulsion-evaporation method with Precirol ATO 5 and Geleol as lipids and Pluronic F 68 as surfactant and optimized with Box-Behnken design for particle size and entrapment efficiency. SLNs were incorporated into the transmucosal patch (TP) prepared with hydroxypropyl cellulose-LF (HPC-LF) and with a backing layer of ethyl cellulose. Optimized SLNs and TP were characterized for Fourier transform infrared spectrophotometry, differential scanning calorimetry, scanning electron microscopy, X-ray diffraction, in vitro release, ex vivo permeation through porcine buccal mucosa, Caco-2 permeability, and residual solvent analysis by gas chromatography. The TP was also evaluated for swelling index, in vitro residence time, tensile strength, and mucoadhesive strength. Preclinical pharmacokinetic, pharmacodynamic, and histopathological studies by application of TP on the gingiva of New Zealand rabbits were carried out. Particle size and entrapment efficiency of the optimized SLN "S8" were determined as 98.23 nm and 84.36%, respectively. The gingival crevicular fluid and tissue concentrations were greater than plasma concentrations with increase in C max and area under the curve (AUC) of Lig and Dic when compared to the control group. Pain perception by needle prick showed prolonged combined anesthetic and analgesic effect. The developed TP loaded with Lig base and Dic diethylamine-SLNs exhibited immediate and complete permeation with tissue accumulation of Lig followed by controlled prolonged release and tissue accumulation of Dic at the site of application. Thus, it could be anticipated from the in vivo studies that the developed TP provides immediate initial anesthetic effect, and the analgesic effect would be prolonged for 24 hours, since optimal gingival crevicular fluid and tissue levels of analgesic would be achieved, while the tissue remains anesthetized.

LIGS measurements in the nozzle reservoir of a free-piston shock tunnel

NASA Astrophysics Data System (ADS)

Altenhöfer, P.; Sander, T.; Koroll, F.; Mundt, Ch.

2018-02-01

Free-piston shock tunnels are ground-based test facilities allowing the simulation of reentry flow conditions in a simple and cost-efficient way. For a better understanding of the processes occurring in a shock tunnel as well as for an optimal comparability of experimental data gained in shock tunnels to numerical simulations, it is highly desirable to have the best possible characterization of the generated test gas flows. This paper describes the final step of the development of a laser-induced grating spectroscopy (LIGS) system capable of measuring the temperature in the nozzle reservoir of a free-piston shock tunnel during tests: the successful adaptation of the measurement system to the shock tunnel. Preliminary measurements were taken with a high-speed camera and a LED lamp in order to investigate the optical transmissibility of the measurement volume during tests. The results helped to successfully measure LIGS signals in shock tube mode and shock tunnel mode in dry air seeded with NO. For the shock tube mode, six successful measurements for a shock Mach number of about 2.35 were taken in total, two of them behind the incoming shock (p ≈ 1 MPa, T ≈ 600 K) and four after the passing of the reflected shock (p ≈ 4 MPa, T ≈ 1000 K). For five of the six measurements, the derived temperatures were within a deviation range of 6% to a reference value calculated from measured shock speed. The uncertainty estimated was less than or equal to 3.5% for all six measurements. Two LIGS signals from measurements behind the reflected shock in shock tunnel mode were analyzed in detail. One of the signals allowed an unambiguous derivation of the temperature under the conditions of a shock with Mach 2.7 (p ≈ 5 MPa, T ≈ 1200 K, deviation 0.5% , uncertainty 4.9% ).

Single-Nucleotide Polymorphisms of Genes Involved in Repair of Oxidative DNA Damage and the Risk of Recurrent Depressive Disorder.

PubMed

Czarny, Piotr; Kwiatkowski, Dominik; Toma, Monika; Gałecki, Piotr; Orzechowska, Agata; Bobińska, Kinga; Bielecka-Kowalska, Anna; Szemraj, Janusz; Berk, Michael; Anderson, George; Śliwiński, Tomasz

2016-11-20

BACKGROUND Depressive disorder, including recurrent type (rDD), is accompanied by increased oxidative stress and activation of inflammatory pathways, which may induce DNA damage. This thesis is supported by the presence of increased levels of DNA damage in depressed patients. Such DNA damage is repaired by the base excision repair (BER) pathway. BER efficiency may be influenced by polymorphisms in BER-related genes. Therefore, we genotyped nine single-nucleotide polymorphisms (SNPs) in six genes encoding BER proteins. MATERIAL AND METHODS Using TaqMan, we selected and genotyped the following SNPs: c.-441G>A (rs174538) of FEN1, c.2285T>C (rs1136410) of PARP1, c.580C>T (rs1799782) and c.1196A>G (rs25487) of XRCC1, c.*83A>C (rs4796030) and c.*50C>T (rs1052536) of LIG3, c.-7C>T (rs20579) of LIG1, and c.-468T>G (rs1760944) and c.444T>G (rs1130409) of APEX1 in 599 samples (288 rDD patients and 311 controls). RESULTS We found a strong correlation between rDD and both SNPs of LIG3, their haplotypes, as well as a weaker association with the c.-468T>G of APEXI which diminished after Nyholt correction. Polymorphisms of LIG3 were also associated with early onset versus late onset depression, whereas the c.-468T>G polymorphism showed the opposite association. CONCLUSIONS The SNPs of genes involved in the repair of oxidative DNA damage may modulate rDD risk. Since this is an exploratory study, the results should to be treated with caution and further work needs to be done to elucidate the exact involvement of DNA damage and repair mechanisms in the development of this disease.

Single-Nucleotide Polymorphisms of Genes Involved in Repair of Oxidative DNA Damage and the Risk of Recurrent Depressive Disorder

PubMed Central

Czarny, Piotr; Kwiatkowski, Dominik; Toma, Monika; Gałecki, Piotr; Orzechowska, Agata; Bobińska, Kinga; Bielecka-Kowalska, Anna; Szemraj, Janusz; Berk, Michael; Anderson, George; Śliwiński, Tomasz

2016-01-01

Background Depressive disorder, including recurrent type (rDD), is accompanied by increased oxidative stress and activation of inflammatory pathways, which may induce DNA damage. This thesis is supported by the presence of increased levels of DNA damage in depressed patients. Such DNA damage is repaired by the base excision repair (BER) pathway. BER efficiency may be influenced by polymorphisms in BER-related genes. Therefore, we genotyped nine single-nucleotide polymorphisms (SNPs) in six genes encoding BER proteins. Material/Methods Using TaqMan, we selected and genotyped the following SNPs: c.-441G>A (rs174538) of FEN1, c.2285T>C (rs1136410) of PARP1, c.580C>T (rs1799782) and c.1196A>G (rs25487) of XRCC1, c.*83A>C (rs4796030) and c.*50C>T (rs1052536) of LIG3, c.-7C>T (rs20579) of LIG1, and c.-468T>G (rs1760944) and c.444T>G (rs1130409) of APEX1 in 599 samples (288 rDD patients and 311 controls). Results We found a strong correlation between rDD and both SNPs of LIG3, their haplotypes, as well as a weaker association with the c.-468T>G of APEXI which diminished after Nyholt correction. Polymorphisms of LIG3 were also associated with early onset versus late onset depression, whereas the c.-468T>G polymorphism showed the opposite association. Conclusions The SNPs of genes involved in the repair of oxidative DNA damage may modulate rDD risk. Since this is an exploratory study, the results should to be treated with caution and further work needs to be done to elucidate the exact involvement of DNA damage and repair mechanisms in the development of this disease. PMID:27866211

High-Performance Biomass-Based Flexible Solid-State Supercapacitor Constructed of Pressure-Sensitive Lignin-Based and Cellulose Hydrogels.

PubMed

Peng, Zhiyuan; Zou, Yubo; Xu, Shiqi; Zhong, Wenbin; Yang, Wantai

2018-06-19

Employing renewable, earth-abundant, environmentally friendly, low-cost natural materials to design flexible supercapacitors (FSCs) as energy storage devices in wearable/portable electronics represents the global perspective to build sustainable and green society. Chemically stable and flexible cellulose and electroactive lignin have been employed to construct a biomass-based FSC for the first time. The FSC was assembled using lignosulfonate/single-walled carbon nanotube HNO 3 (Lig/SWCNT HNO 3 ) pressure-sensitive hydrogels as electrodes and cellulose hydrogels as an electrolyte separator. The assembled biomass-based FSC shows high specific capacitance (292 F g -1 at a current density of 0.5 A g -1 ), excellent rate capability, and an outstanding energy density of 17.1 W h kg -1 at a power density of 324 W kg -1 . Remarkably, the FSC presents outstanding electrochemical stability even suffering 1000 bending cycles. Such excellent flexibility, stability, and electrochemical performance enable the designed biomass-based FSCs as prominent candidates in applications of wearable electronic devices.

Differential in vivo gene expression of major Leptospira proteins in resistant or susceptible animal models.

PubMed

Matsui, Mariko; Soupé, Marie-Estelle; Becam, Jérôme; Goarant, Cyrille

2012-09-01

Transcripts of Leptospira 16S rRNA, FlaB, LigB, LipL21, LipL32, LipL36, LipL41, and OmpL37 were quantified in the blood of susceptible (hamsters) and resistant (mice) animal models of leptospirosis. We first validated adequate reference genes and then evaluated expression patterns in vivo compared to in vitro cultures. LipL32 expression was downregulated in vivo and differentially regulated in resistant and susceptible animals. FlaB expression was also repressed in mice but not in hamsters. In contrast, LigB and OmpL37 were upregulated in vivo. Thus, we demonstrated that a virulent strain of Leptospira differentially adapts its gene expression in the blood of infected animals.

Novel Bioactive Antimicrobial Lignin Containing Coatings on Titanium Obtained by Electrophoretic Deposition

PubMed Central

Erakovic, Sanja; Jankovic, Ana; Tsui, Gary C. P.; Tang, Chak-Yin; Miskovic-Stankovic, Vesna; Stevanovic, Tatjana

2014-01-01

Hydroxyapatite (HAP) is the most suitable biocompatible material for bone implant coatings; its brittleness, however, is a major obstacle, and the reason why research focuses on creating composites with biopolymers. Organosolv lignin (Lig) is used for the production of composite coatings, and these composites were examined in this study. Titanium substrate is a key biomedical material due to its well-known properties, but infections of the implantation site still impose a serious threat. One approach to prevent infection is to improve antimicrobial properties of the coating material. Silver doped hydroxyapatite (Ag/HAP) and HAP coatings on titanium were obtained by an electrophoretic deposition method in order to control deposited coating mass and morphology by varying applied voltage and deposition time. The effect of lignin on microstructure, morphology and thermal behavior of biocomposite coatings was investigated. The results showed that higher lignin concentrations protect the HAP lattice during sintering, improving coating stability. The corrosion stability was evaluated in simulated body fluid (SBF) at 37 °C. Newly formed plate-shaped carbonate-HAP was detected, indicating enhanced bioactive performance. The antimicrobial efficiency of Ag/HAP/Lig was confirmed by its higher reduction of bacteria Staphylococcus aureus TL (S. aureus TL) than of HAP/Lig coating. Cytotoxicity assay revealed that both coatings can be classified as non-toxic against healthy immunocompetent peripheral blood mononuclear cells (PBMC). PMID:25019343

Novel bioactive antimicrobial lignin containing coatings on titanium obtained by electrophoretic deposition.

PubMed

Erakovic, Sanja; Jankovic, Ana; Tsui, Gary C P; Tang, Chak-Yin; Miskovic-Stankovic, Vesna; Stevanovic, Tatjana

2014-07-11

Hydroxyapatite (HAP) is the most suitable biocompatible material for bone implant coatings; its brittleness, however, is a major obstacle, and the reason why research focuses on creating composites with biopolymers. Organosolv lignin (Lig) is used for the production of composite coatings, and these composites were examined in this study. Titanium substrate is a key biomedical material due to its well-known properties, but infections of the implantation site still impose a serious threat. One approach to prevent infection is to improve antimicrobial properties of the coating material. Silver doped hydroxyapatite (Ag/HAP) and HAP coatings on titanium were obtained by an electrophoretic deposition method in order to control deposited coating mass and morphology by varying applied voltage and deposition time. The effect of lignin on microstructure, morphology and thermal behavior of biocomposite coatings was investigated. The results showed that higher lignin concentrations protect the HAP lattice during sintering, improving coating stability. The corrosion stability was evaluated in simulated body fluid (SBF) at 37 °C. Newly formed plate-shaped carbonate-HAP was detected, indicating enhanced bioactive performance. The antimicrobial efficiency of Ag/HAP/Lig was confirmed by its higher reduction of bacteria Staphylococcus aureus TL (S. aureus TL) than of HAP/Lig coating. Cytotoxicity assay revealed that both coatings can be classified as non-toxic against healthy immunocompetent peripheral blood mononuclear cells (PBMC).

Simulating climate and stable water isotopes during the Last Interglacial using a coupled climate-isotope model

NASA Astrophysics Data System (ADS)

Gierz, Paul; Werner, Martin; Lohmann, Gerrit

2017-09-01

Understanding the dynamics of warm climate states has gained increasing importance in the face of anthropogenic climate change, and while it is possible to simulate warm interglacial climates, these simulated results cannot be evaluated without the aid of geochemical proxies. One such proxy is δ18O, which allows for inference about both a climate state's hydrology and temperature. We utilize a stable water isotope equipped climate model to simulate three stages during the Last Interglacial (LIG), corresponding to 130, 125, and 120 kyr before present, using forcings for orbital configuration as well as greenhouse gases. We discover heterogeneous responses in the mean δ18O signal to the climate forcing, with large areas of depletion in the LIG δ18O signal over the tropical Atlantic, the Sahel, and the Indian subcontinent, and with enrichment over the Pacific and Arctic Oceans. While we find that the climatology mean relationship between δ18O and temperature remains stable during the LIG, we also discover that this relationship is not spatially consistent. Our results suggest that great care must be taken when comparing δ18O records of different paleoclimate archives with the results of climate models as both the qualitative and quantitative interpretation of δ18O variations as a proxy for past temperature changes may be problematic due to the complexity of the signals.

Differential In Vivo Gene Expression of Major Leptospira Proteins in Resistant or Susceptible Animal Models

PubMed Central

Matsui, Mariko; Soupé, Marie-Estelle; Becam, Jérôme

2012-01-01

Transcripts of Leptospira 16S rRNA, FlaB, LigB, LipL21, LipL32, LipL36, LipL41, and OmpL37 were quantified in the blood of susceptible (hamsters) and resistant (mice) animal models of leptospirosis. We first validated adequate reference genes and then evaluated expression patterns in vivo compared to in vitro cultures. LipL32 expression was downregulated in vivo and differentially regulated in resistant and susceptible animals. FlaB expression was also repressed in mice but not in hamsters. In contrast, LigB and OmpL37 were upregulated in vivo. Thus, we demonstrated that a virulent strain of Leptospira differentially adapts its gene expression in the blood of infected animals. PMID:22729538

Reconstruction of the Eemian climate using a fully coupled Earth system model

NASA Astrophysics Data System (ADS)

Rybak, Oleg; Volodin, Evgeny; Morozova, Polina; Huybrechts, Philippe

2017-04-01

Climate of the Last Interglacial (LIG) between ca. 130 and 115 kyr BP is thought to be a good analogue for future climate warming. Though the driving mechanisms of the past and current climate evolution differ, analysis of the LIG climate may provide important insights for projections of future environmental changes. We do not know properly what was spatial distribution and magnitude of surface air temperature and precipitation anomalies with respect to present. Sparse proxy data are attributed mostly to the continental margins, internal areas of ice sheets and particular regions of the World Ocean. Combining mathematical modeling and indirect evidence can help to identify driving mechanisms and feed-backs which formed climatic conditions of the LIG. In order to reproduce the LIG climate, we carried out transient numerical experiments using a fully coupled Earth System Model (ESM) consisting of an AO GCM, which includes decription of the biosphere, atmospheric and oceanic chemistry ets. (INMCM), developed in the Institute of Numerical Mathematics (Moscow, Russia) and the models of Greenland and Antarctic ice sheets (GrISM and AISM, Vrije Uninersiteit Brussel, Belgium). Though the newest version of the INMCM has rather high spatial resolution, it canot be used in long transient numerical experimemts because of high computational demand. Coupling of the GrISM and AISM to the low resolution version of the INMCM is complicated by essential differences in spatial and temporal scales of cryospheric, atmosphere and the ocean components of the ESM (spatial resolution 5˚×4˚, 21 vertical layers in the atmospheric block, 2.5°×2°, 6 min. temporal resolution; 33 vertical layers in the oceanic block; 20×20 km, 51 vertical layers and 1 yr temporal resolution in the GrISM and AISM). We apply two different coupling strategies. AISM is incorporated into the ESM via using procedures of resampling and interpolation of the input fields of annually averaged air surface temperatures and precipitation fields generated by the INMCM. To provide interactive coupling of the INMCM and the GrISM, we employ a special energy- and water balance model (EWBM-G), which serves as a buffer providing effective data exchange between sub-models. EWBM-G operates in a rectangle domain including Greenland and calculates annual surface mass balance (further transferred as an external forcing to the GrISM) and fresh water flux (transferred to the oceanic block of the INMCM). Orbital parameters of the LIG were set with 1 kyr step with further interpolation to 100 years. Assuming concentrations of greenhouse gases during the LIG were not very much different from the preindustrial values, this potential forcing was neglected. Climatic block of the ESM was called every 100 model years to follow changes in orbital forcing. AISM and GrISM were asynchronously coupled to sub-models of the atmosphere and the ocean with the ratio of model years as 100 to 1. Obtained fields of deviations of air surface temperature from preindustrial values correspond in general to the estimates made in earlier studies. Evaluated contribution of the Greenland ice sheet to the global sea level rise (approximately 2 m) supports the newest estimates based on model results and proxy data analysis.

Topical anaesthesia reduces sensitivity of castration wounds in neonatal piglets

PubMed Central

Windsor, Peter A.

2017-01-01

The aim of this study was to do determine the efficacy of the topical anaesthetic Tri-Solfen® in the amelioration of the pain of castration in piglets. The trial was conducted over a three day period, and blocked across six litters with 12 piglets treated on days one and two, and 16 on day three. The piglets were randomly allocated by weight and litter to 1 of 4 treatment groups: (i) sham castration (SHAM; n = 10); (ii) surgical castration with no anaesthetic intervention (CAST; n = 10); (iii) surgical castration with post-operative topical anaesthesia (TRI; n = 10); (iv) surgical castration with a pre-operative intra-testicular lignocaine hydrochloride injection (LIG; n = 10). Wound sensitivity testing involved von Frey monofilaments of weights 4g and 300g, and an 18 gauge needle, used to stimulate the wound and surrounding skin respectively, at various pre-determined sites. Neonatal piglets receiving topical anaesthesia (Tri-Solfen®) spray into castration wounds had significantly lower wound sensitivity responses for up to 4h, compared to those castrated following intra-testicular lignocaine injection or those with no treatment. The use of topical anaesthetic is suggested as a practical and affordable method of improving piglet welfare during castration. PMID:29140997

Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission.

PubMed

Church, Jessica D; Omer, Saad B; Guay, Laura A; Huang, Wei; Lidstrom, Jessica; Musoke, Philippa; Mmiro, Francis; Jackson, J Brooks; Eshleman, Susan H

2008-10-01

Single-dose nevirapine (SD NVP) at birth plus NVP prophylaxis for the infant up to 6 weeks of age is superior to SD NVP alone for prevention of vertical transmission of human immunodeficiency virus (HIV) through breastfeeding. We analyzed NVP resistance in HIV-infected Ugandan infants who received either SD NVP or extended NVP prophylaxis. We tested plasma HIV by using a genotyping assay (ViroSeq; Celera Diagnostics), a phenotypic resistance assay (PhenoSense; Monogram Biosciences), and sensitive point mutation assay (LigAmp, for K103N, Y181C, and G190A). When infants were 6 weeks old, ViroSeq detected NVP resistance in a higher proportion of infants in the extended NVP arm than in the SD NVP arm (21 of 25 [84%] vs. 12 of 24 [50%]; P = .01). Similar results were obtained with LigAmp and PhenoSense. In both study arms, infants who were HIV infected at birth frequently had NVP resistance detected. In contrast, infants in the extended NVP arm who were HIV infected after birth were more likely to have resistance detected at 6 weeks, compared with infants in the SD NVP arm. The use of extended NVP prophylaxis was also associated with detection of NVP resistance by ViroSeq at 6 months (7 of 7 [100%] infants in the extended NVP arm had resistance detected, compared with 1 of 6 [16.7%] infants in the SD NVP arm; P = .005). The use of extended NVP prophylaxis was associated with increased selection for and persistence of NVP resistance in HIV-infected Ugandan infants.

Elucidation of Transport Mechanism of Paeoniflorin and the Influence of Ligustilide, Senkyunolide I and Senkyunolide A on Paeoniflorin Transport through Mdck-Mdr1 Cells as Blood-Brain Barrier in Vitro Model.

PubMed

Hu, Peng-Yi; Liu, Dan; Zheng, Qin; Wu, Qing; Tang, Yu; Yang, Ming

2016-03-02

The objectives of the present investigation were to: (1) elucidate the transport mechanism of paeoniflorin (PF) across MDCK-MDR1 monolayers; and (2) evaluate the effect of ligustilide (LIG), senkyunolide I (SENI) and senkyunolide A (SENA) on the transport of PF through blood-brain barrier so as to explore the enhancement mechanism. Transport studies of PF were performed in both directions, from apical to basolateral side (A→B) and from basolateral to apical sides (B→A). Drug concentrations were analyzed by LC-MS/MS. PF showed relatively poor absorption in MDCK-MDR1 cells, apparent permeability coefficients (Papp) ranging from 0.587 × 10(-6) to 0.705 × 10(-6) cm/s. In vitro experiments showed that the transport of PF in both directions was concentration dependent and not saturable. The B→A/A→B permeability ER of PF was more than 2 in the MDCK-MDR1 cells, which indicated that the transport mechanism of PF might be passive diffusion as the dominating process with the active transportation mediated mechanism involved. The increased Papp of PF in A→B direction by EDTA-Na₂ suggested that PF was absorbed via the paracellular route. The P-gp inhibitor verapamil could significantly increase the transport of PF in A→B direction, and ER decreased from 2.210 to 0.690, which indicated that PF was P-gp substance. The transport of PF in A→B direction significantly increased when co-administrated with increasing concentrations of LIG, SENI and SENA. An increased cellular accumulation of Rho 123 and Western blot analysis indicated that LIG, SENI and SENA had increased the transport of PF in the BBB models attribute to down-regulate P-gp expression. A decrease in transepithelial electrical resistance (TEER) during the permeation experiment can be explained by the modulation and opening of the tight junctions caused by the permeation enhancer LIG, SENI and SENA.

Development of transmucosal patch loaded with anesthetic and analgesic for dental procedures and in vivo evaluation

PubMed Central

Nidhi, Malviya; Patro, M Nagaraju; Kusumvalli, Somisetty; Kusumdevi, Vemula

2016-01-01

Most of the dental surgeries require preoperative anesthetic and postoperative analgesic for painless procedures. A multidrug transmucosal drug delivery system loaded with lignocaine (Lig) base for immediate release and solid lipid nanoparticles (SLNs) of diclofenac (Dic) diethylamine for prolonged release was developed. SLNs were prepared by solvent emulsion–evaporation method with Precirol ATO 5 and Geleol as lipids and Pluronic F 68 as surfactant and optimized with Box–Behnken design for particle size and entrapment efficiency. SLNs were incorporated into the transmucosal patch (TP) prepared with hydroxypropyl cellulose-LF (HPC-LF) and with a backing layer of ethyl cellulose. Optimized SLNs and TP were characterized for Fourier transform infrared spectrophotometry, differential scanning calorimetry, scanning electron microscopy, X-ray diffraction, in vitro release, ex vivo permeation through porcine buccal mucosa, Caco-2 permeability, and residual solvent analysis by gas chromatography. The TP was also evaluated for swelling index, in vitro residence time, tensile strength, and mucoadhesive strength. Preclinical pharmacokinetic, pharmacodynamic, and histopathological studies by application of TP on the gingiva of New Zealand rabbits were carried out. Particle size and entrapment efficiency of the optimized SLN “S8” were determined as 98.23 nm and 84.36%, respectively. The gingival crevicular fluid and tissue concentrations were greater than plasma concentrations with increase in Cmax and area under the curve (AUC) of Lig and Dic when compared to the control group. Pain perception by needle prick showed prolonged combined anesthetic and analgesic effect. The developed TP loaded with Lig base and Dic diethylamine-SLNs exhibited immediate and complete permeation with tissue accumulation of Lig followed by controlled prolonged release and tissue accumulation of Dic at the site of application. Thus, it could be anticipated from the in vivo studies that the developed TP provides immediate initial anesthetic effect, and the analgesic effect would be prolonged for 24 hours, since optimal gingival crevicular fluid and tissue levels of analgesic would be achieved, while the tissue remains anesthetized. PMID:27382279

Lignolytic-consortium omics analyses reveal novel genomes and pathways involved in lignin modification and valorization.

PubMed

Moraes, Eduardo C; Alvarez, Thabata M; Persinoti, Gabriela F; Tomazetto, Geizecler; Brenelli, Livia B; Paixão, Douglas A A; Ematsu, Gabriela C; Aricetti, Juliana A; Caldana, Camila; Dixon, Neil; Bugg, Timothy D H; Squina, Fabio M

2018-01-01

Lignin is a heterogeneous polymer representing a renewable source of aromatic and phenolic bio-derived products for the chemical industry. However, the inherent structural complexity and recalcitrance of lignin makes its conversion into valuable chemicals a challenge. Natural microbial communities produce biocatalysts derived from a large number of microorganisms, including those considered unculturable, which operate synergistically to perform a variety of bioconversion processes. Thus, metagenomic approaches are a powerful tool to reveal novel optimized metabolic pathways for lignin conversion and valorization. The lignin-degrading consortium (LigMet) was obtained from a sugarcane plantation soil sample. The LigMet taxonomical analyses (based on 16S rRNA) indicated prevalence of Proteobacteria , Actinobacteria and Firmicutes members, including the Alcaligenaceae and Micrococcaceae families, which were enriched in the LigMet compared to sugarcane soil. Analysis of global DNA sequencing revealed around 240,000 gene models, and 65 draft bacterial genomes were predicted. Along with depicting several peroxidases, dye-decolorizing peroxidases, laccases, carbohydrate esterases, and lignocellulosic auxiliary (redox) activities, the major pathways related to aromatic degradation were identified, including benzoate (or methylbenzoate) degradation to catechol (or methylcatechol), catechol ortho-cleavage, catechol meta-cleavage, and phthalate degradation. A novel Paenarthrobacter strain harboring eight gene clusters related to aromatic degradation was isolated from LigMet and was able to grow on lignin as major carbon source. Furthermore, a recombinant pathway for vanillin production was designed based on novel gene sequences coding for a feruloyl-CoA synthetase and an enoyl-CoA hydratase/aldolase retrieved from the metagenomic data set. The enrichment protocol described in the present study was successful for a microbial consortium establishment towards the lignin and aromatic metabolism, providing pathways and enzyme sets for synthetic biology engineering approaches. This work represents a pioneering study on lignin conversion and valorization strategies based on metagenomics, revealing several novel lignin conversion enzymes, aromatic-degrading bacterial genomes, and a novel bacterial strain of potential biotechnological interest. The validation of a biosynthetic route for vanillin synthesis confirmed the applicability of the targeted metagenome discovery approach for lignin valorization strategies.

New endoscopic platform for endoluminal en bloc tissue resection in the gastrointestinal tract (with videos).

PubMed

Kantsevoy, Sergey V; Bitner, Marianne; Piskun, Gregory

2016-07-01

Endoscopic removal of gastrointestinal tract lesions is increasingly popular around the world. We evaluated feasibility, safety, effectiveness, and user learning curve of new endoscopic platform for complex intraluminal interventions. A novel system, consisting of expandable working chamber with two independent instrument guides (LIG), was inserted into colon. Simulated colonic lesions were removed with endoscopic submucosal (ESD) and submuscular (ESmD) dissection. In all nine in vivo models, an intraluminal chamber and its dynamic tissue retractors (via LIG) provided a stable working space with excellent visualization and adequate access to target tissue. Endoscopic platform facilitated successful completion of 11 en bloc ESDs (mean size 43.0 ± 11.3 mm, mean time 46.3 ± 41.2 min) and eight ESmD (mean size 50.0 ± 14.1 mm, mean time 48.0 ± 21.2 min). The learning curve for ESD using this platform demonstrated three phases: rapid improvement in procedural skills took place during the first three procedures (mean ESD time 98.7 ± 40.0 min). A plateau phase then occurred (procedures 4-7) with mean procedure time 42.0 ± 13.4 min (p = 0.04), followed by another sharp improvement in procedural skills (procedures 8-11) requiring only 16.3 ± 11.4 min (p = 0.03) to complete ESD. Especially dramatic (p = 0.002) was the time difference between the first three procedures (mean time 98.7 ± 40.0 min) and subsequent eight procedures (mean time 29.1 ± 17.9 min). A newly developed endoscopic platform provides stable intraluminal working space, dynamic tissue retraction, and instrument triangulation, improving visualization and access to the target tissue for safer and more effective en bloc endoscopic submucosal and submuscular dissection. The learning curve for ESD was markedly facilitated by this new endoscopic platform.

Theoretical study of the hydrolysis mechanism of 2-pyrone-4,6-dicarboxylate (PDC) catalyzed by LigI.

PubMed

Zhang, Shujun; Ma, Guangcai; Liu, Yongjun; Ling, Baoping

2015-09-01

2-Pyrone-4,6-dicarboxylate lactonase (LigI) is the first identified enzyme from amidohydrolase superfamily that does not require a divalent metal ion for catalytic activity. It catalyzes the reversible hydrolysis of 2-pyrone-4,6-dicarboxylate (PDC) to 4-oxalomesaconate (OMA) and 4-carboxy-2-hydroxymuconate (CHM) in the degradation of lignin. In this paper, a combined quantum mechanics and molecule mechanics (QM/MM) approach was employed to study the reaction mechanism of LigI from Sphingomonas paucimobilis. According to the results of our calculations, the whole catalytic reaction contains three elementary steps, including the nucleophilic attack, the cleavage of CO of lactone (substrate) and the intramolecular proton transfer. The intermediate has two intramolecular proton transfer pathways, due to which, two final hydrolysis products can be obtained. The energy profile indicates that 4-carboxy-2-hydroxymuconate (CHM) is the main hydrolysis product, therefore, the isomerization between 4-carboxy-2-hydroxymuconate (CHM) and 4-oxalomesaconate (OMA) is suggested to occur in solvent. During the catalytic reaction, residue Asp248 acts as a general base to activate the hydrolytic water molecule. Although His31, His33 and His180 do not directly participate in the chemical process, they play assistant roles by forming electrostatic interactions with the substrate and its involved species in activating the carbonyl group of the substrate and stabilizing the intermediates and transition states. Copyright © 2015 Elsevier Inc. All rights reserved.

Characteristics and synergistic effects of co-combustion of carbonaceous wastes with coal.

PubMed

Onenc, Sermin; Retschitzegger, Stefan; Evic, Nikola; Kienzl, Norbert; Yanik, Jale

2018-01-01

This study presents combustion behavior and emission results obtained for different fuels: poultry litter (PL) and its char (PLC), scrap tires (ST) and its char (STC) and blends of char/lignite (PLC/LIG and STC/LIG). The combustion parameters and emissions were investigated via a non-isothermal thermogravimetric method and experiments in a lab-scale reactor. Fuel indexes were used for the prediction of high temperature corrosion risks and slagging potentials of the fuels used. The addition of chars to lignite caused a lowering of the combustion reactivity (anti-synergistic effect). There was a linear correlation between the NO x emissions and the N content of the fuel. The form of S and the concentrations of alkali metals in the fuel had a strong effect on the extent of SO 2 emissions. The use of PL and PLC in blends reduced SO 2 emissions and sulphur compounds in the fly ash. The 2S/Cl ratio in the fuel showed that only PLC and STC/PLC would show a risk of corrosion during combustion. The ratio of basic to acidic oxides in fuel indicated that ST, STC and STC/LIG have low slagging potential. The molar (Si+P+K)/(Ca+Mg) ratio, which was used for PL, PLC and PLC containing blends, showed that the ash melting temperatures of these fuels would be higher than 1000 °C. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mutations in the NHEJ Component XRCC4 Cause Primordial Dwarfism

PubMed Central

Murray, Jennie E.; van der Burg, Mirjam; IJspeert, Hanna; Carroll, Paula; Wu, Qian; Ochi, Takashi; Leitch, Andrea; Miller, Edward S.; Kysela, Boris; Jawad, Alireza; Bottani, Armand; Brancati, Francesco; Cappa, Marco; Cormier-Daire, Valerie; Deshpande, Charu; Faqeih, Eissa A.; Graham, Gail E.; Ranza, Emmanuelle; Blundell, Tom L.; Jackson, Andrew P.; Stewart, Grant S.; Bicknell, Louise S.

2015-01-01

Non-homologous end joining (NHEJ) is a key cellular process ensuring genome integrity. Mutations in several components of the NHEJ pathway have been identified, often associated with severe combined immunodeficiency (SCID), consistent with the requirement for NHEJ during V(D)J recombination to ensure diversity of the adaptive immune system. In contrast, we have recently found that biallelic mutations in LIG4 are a common cause of microcephalic primordial dwarfism (MPD), a phenotype characterized by prenatal-onset extreme global growth failure. Here we provide definitive molecular genetic evidence supported by biochemical, cellular, and immunological data for mutations in XRCC4, encoding the obligate binding partner of LIG4, causing MPD. We report the identification of biallelic mutations in XRCC4 in five families. Biochemical and cellular studies demonstrate that these alterations substantially decrease XRCC4 protein levels leading to reduced cellular ligase IV activity. Consequently, NHEJ-dependent repair of ionizing-radiation-induced DNA double-strand breaks is compromised in XRCC4 cells. Similarly, immunoglobulin junctional diversification is impaired in cells. However, immunoglobulin levels are normal, and individuals lack overt signs of immunodeficiency. Additionally, in contrast to individuals with LIG4 mutations, pancytopenia leading to bone marrow failure has not been observed. Hence, alterations that alter different NHEJ proteins give rise to a phenotypic spectrum, from SCID to extreme growth failure, with deficiencies in certain key components of this repair pathway predominantly exhibiting growth deficits, reflecting differential developmental requirements for NHEJ proteins to support growth and immune maturation. PMID:25728776

REGULATION OF VASCULOGENESIS AND ANGIOGENESIS

EPA Science Inventory

Regulation of vasculogenesis and angiogenesis.
B.D. Abbott
Reproductive Toxicology Division, Environmental Protection Agency, Research Triangle Park, North Carolina, USA
Vasculogenesis and angiogenesis are regulated by a complex, interactive family of receptors and lig...

75 FR 50760 - Crosstex LIG, LLC; Notice of Filing

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-17

..., clarify the nature in which certain gas accounting will be managed, and to change certain situational... interventions in lieu of paper using the ``eFiling'' link at http://www.ferc.gov . Persons unable to file...

Extended low-resolution structure of a Leptospira antigen offers high bactericidal antibody accessibility amenable to vaccine design

PubMed Central

Tseng, Andrew; Suguiura, Igor Massahiro de Souza; McDonough, Sean P; Sritrakul, Tepyuda; Li, Ting; Lin, Yi-Pin; Gillilan, Richard E

2017-01-01

Pathogens rely on proteins embedded on their surface to perform tasks essential for host infection. These obligatory structures exposed to the host immune system provide important targets for rational vaccine design. Here, we use a systematically designed series of multi-domain constructs in combination with small angle X-ray scattering (SAXS) to determine the structure of the main immunoreactive region from a major antigen from Leptospira interrogans, LigB. An anti-LigB monoclonal antibody library exhibits cell binding and bactericidal activity with extensive domain coverage complementing the elongated architecture observed in the SAXS structure. Combining antigenic motifs in a single-domain chimeric immunoglobulin-like fold generated a vaccine that greatly enhances leptospiral protection over vaccination with single parent domains. Our study demonstrates how understanding an antigen’s structure and antibody accessible surfaces can guide the design and engineering of improved recombinant antigen-based vaccines. PMID:29210669

Mutations in the NHEJ component XRCC4 cause primordial dwarfism.

PubMed

Murray, Jennie E; van der Burg, Mirjam; IJspeert, Hanna; Carroll, Paula; Wu, Qian; Ochi, Takashi; Leitch, Andrea; Miller, Edward S; Kysela, Boris; Jawad, Alireza; Bottani, Armand; Brancati, Francesco; Cappa, Marco; Cormier-Daire, Valerie; Deshpande, Charu; Faqeih, Eissa A; Graham, Gail E; Ranza, Emmanuelle; Blundell, Tom L; Jackson, Andrew P; Stewart, Grant S; Bicknell, Louise S

2015-03-05

Non-homologous end joining (NHEJ) is a key cellular process ensuring genome integrity. Mutations in several components of the NHEJ pathway have been identified, often associated with severe combined immunodeficiency (SCID), consistent with the requirement for NHEJ during V(D)J recombination to ensure diversity of the adaptive immune system. In contrast, we have recently found that biallelic mutations in LIG4 are a common cause of microcephalic primordial dwarfism (MPD), a phenotype characterized by prenatal-onset extreme global growth failure. Here we provide definitive molecular genetic evidence supported by biochemical, cellular, and immunological data for mutations in XRCC4, encoding the obligate binding partner of LIG4, causing MPD. We report the identification of biallelic mutations in XRCC4 in five families. Biochemical and cellular studies demonstrate that these alterations substantially decrease XRCC4 protein levels leading to reduced cellular ligase IV activity. Consequently, NHEJ-dependent repair of ionizing-radiation-induced DNA double-strand breaks is compromised in XRCC4 cells. Similarly, immunoglobulin junctional diversification is impaired in cells. However, immunoglobulin levels are normal, and individuals lack overt signs of immunodeficiency. Additionally, in contrast to individuals with LIG4 mutations, pancytopenia leading to bone marrow failure has not been observed. Hence, alterations that alter different NHEJ proteins give rise to a phenotypic spectrum, from SCID to extreme growth failure, with deficiencies in certain key components of this repair pathway predominantly exhibiting growth deficits, reflecting differential developmental requirements for NHEJ proteins to support growth and immune maturation. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Oleaceae cross-reactions as potential pollinosis cause in urban areas.

PubMed

Vara, A; Fernández-González, M; Aira, M J; Rodríguez-Rajo, F J

2016-01-15

It is worth noting the allergological problems induced by a not accurate design of the ornamental vegetation in the parks and streets of the cities. Usually, in the Oleaceae family, only the olive pollen is considered an important aeroallergen but other species of the family could be an important source of airborne pollen allergens. Pollen from Fraxinus, Olea and Ligustrum and its main aeroallergens were sampled in the atmosphere of an urban area in North-Western Spain during 2011. The allergen bioaerosol content was quantified by using specific 2-site ELISA and Ole e 1 antibodies. The Fra e 1 and Lig v 1 allergens were detected by means Ole e 1 antibodies. This fact demonstrates the cross-reactivity between the main allergens of Fraxinus, Olea and Ligustrum, plants widely species used as ornamental in the cities. Therefore, the urban allergenic people sensitized to Olea pollen could present allergenic reactions during the winter (due to ash pollen allergens), the spring (caused by olive pollen allergens) and the early summer (triggered by the privet flowering). As a consequence, sensitivity to the pollen of one species may favour development of sensitivity to all three species as consequence of the priming effect. The combination of pollen count and the allergen quantification must be assessed in the epidemiologic study of allergic respiratory diseases.

Evaluation of solar-powered raised pavement markers.

DOT National Transportation Integrated Search

2008-01-01

An evaluation of a limited number of solar-powered raised pavement markers (SRPMs) was conducted to : determine if this type of marker would be more visible than retroreflective markers in some situations on : Oregon highways. SRPMs typically use Lig...

Comparison of genome engineering using the CRISPR-Cas9 system in C. glabrata wild-type and lig4 strains.

PubMed

Cen, Yuke; Timmermans, Bea; Souffriau, Ben; Thevelein, Johan M; Van Dijck, Patrick

2017-10-01

Candida glabrata is reported as the second most prevalent human opportunistic fungal pathogen in North America and is threatening patients all over the world. Its incidence is rising, while it has developed resistance to the most widely used antifungal drugs, necessitating new approaches based on better insight into the biology of the organism. Despite its close phylogenetic relationship with Saccharomyces cerevisiae, generating precise genomic alterations in this species is problematic. Previously we have shown that deletion of LIG4, which encodes an enzyme involved in Non-Homologous End Joining (NHEJ), strongly enhances the probability of obtaining correctly modified transformants. In this work we used the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR associated protein 9 (Cas9) system to genetically engineer the C. glabrata genome, targeting the genes ADE2, MET15 and SOK2, located on different chromosomes. We used the CRISPR-Cas9 technology to replace the open reading frame (ORF) by the SAT1 selective marker or introduced a premature stop codon in ADE2 and MET15, as they are easily scored by their adenine or methionine auxotrophy, respectively. The SOK2 gene was modified by insertion of a triple HA-tag sequence and the transformants were verified in a western blot. The CRISPR-Cas9 mediated targeting efficiency varies depending on the gene targeted and the genetic modification performed. We show that CRISPR-Cas9 mediated genome editing is more efficient than the conventional method in the wild-type strain, moreover it has the big advantage being marker-free. In previous work, we showed that the targeting efficiency is highly increased in the lig4Δ strain using the conventional way to delete genes in C. glabrata. Using the CRISPR-Cas9 system in this strain, the percentage of correct transformants is consistently higher compared to the wild-type strain. This indicates that using the lig4 mutant as such is already a strong improvement, while the CRISPR-Cas9 gives the additional advantage of not leaving a scar or marker and that it therefore can be used to generate multiple modifications. Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical shift imprint of intersubunit communication in a symmetric homodimer

PubMed Central

Falk, Bradley T.; Sapienza, Paul J.; Lee, Andrew L.

2016-01-01

Allosteric communication is critical for protein function and cellular homeostasis, and it can be exploited as a strategy for drug design. However, unlike many protein–ligand interactions, the structural basis for the long-range communication that underlies allostery is not well understood. This lack of understanding is most evident in the case of classical allostery, in which a binding event in one protomer is sensed by a second symmetric protomer. A primary reason why study of interdomain signaling is challenging in oligomeric proteins is the difficulty in characterizing intermediate, singly bound species. Here, we use an NMR approach to isolate and characterize a singly ligated state (“lig1”) of a homodimeric enzyme that is otherwise obscured by rapid exchange with apo and saturated forms. Mixed labeled dimers were prepared that simultaneously permit full population of the lig1 state and isotopic labeling of either protomer. Direct visualization of peaks from lig1 yielded site-specific ligand-state multiplets that provide a convenient format for assessing mechanisms of intersubunit communication from a variety of NMR measurements. We demonstrate this approach on thymidylate synthase from Escherichia coli, a homodimeric enzyme known to be half-the-sites reactive. Resolving the dUMP1 state shows that active site communication occurs not upon the first dUMP binding, but upon the second. Surprisingly, for many sites, dUMP1 peaks are found beyond the limits set by apo and dUMP2 peaks, indicating that binding the first dUMP pushes the enzyme ensemble to further conformational extremes than the apo or saturated forms. The approach used here should be generally applicable to homodimers. PMID:27466406

Structure and catalytic mechanism of LigI: insight into the amidohydrolase enzymes of cog3618 and lignin degradation.

PubMed

Hobbs, Merlin Eric; Malashkevich, Vladimir; Williams, Howard J; Xu, Chengfu; Sauder, J Michael; Burley, Stephen K; Almo, Steven C; Raushel, Frank M

2012-04-24

LigI from Sphingomonas paucimobilis catalyzes the reversible hydrolysis of 2-pyrone-4,6-dicarboxylate (PDC) to 4-oxalomesaconate and 4-carboxy-2-hydroxymuconate in the degradation of lignin. This protein is a member of the amidohydrolase superfamily of enzymes. The protein was expressed in Escherichia coli and then purified to homogeneity. The purified recombinant enzyme does not contain bound metal ions, and the addition of metal chelators or divalent metal ions to the assay mixtures does not affect the rate of product formation. This is the first enzyme from the amidohydrolase superfamily that does not require a divalent metal ion for catalytic activity. The kinetic constants for the hydrolysis of PDC are 340 s(-1) and 9.8 × 10(6) M(-1) s(-1) (k(cat) and k(cat)/K(m), respectively). The pH dependence on the kinetic constants suggests that a single active site residue must be deprotonated for the hydrolysis of PDC. The site of nucleophilic attack was determined by conducting the hydrolysis of PDC in (18)O-labeled water and subsequent (13)C nuclear magnetic resonance analysis. The crystal structures of wild-type LigI and the D248A mutant in the presence of the reaction product were determined to a resolution of 1.9 Å. The C-8 and C-11 carboxylate groups of PDC are coordinated within the active site via ion pair interactions with Arg-130 and Arg-124, respectively. The hydrolytic water molecule is activated by the transfer of a proton to Asp-248. The carbonyl group of the lactone substrate is activated by electrostatic interactions with His-180, His-31, and His-33.

TGF-β1 accelerates the DNA damage response in epithelial cells via Smad signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Jeeyong; Kim, Mi-Ra; Kim, Hyun-Ji

The evidence suggests that transforming growth factor-beta (TGF-β) regulates the DNA-damage response (DDR) upon irradiation, and we previously reported that TGF-β1 induced DNA ligase IV (Lig4) expression and enhanced the nonhomologous end-joining repair pathway in irradiated cells. In the present study, we investigated the effects of TGF-β1 on the irradiation-induced DDRs of A431 and HaCaT cells. Cells were pretreated with or without TGF-β1 and irradiated. At 30 min post-irradiation, DDRs were detected by immunoblotting of phospho-ATM, phospho-Chk2, and the presence of histone foci (γH2AX). The levels of all three factors were similar right after irradiation regardless of TGF-β1 pretreatment. However, theymore » soon thereafter exhibited downregulation in TGF-β1-pretreated cells, indicating the acceleration of the DDR. Treatment with a TGF-β type I receptor inhibitor (SB431542) or transfections with siRNAs against Smad2/3 or DNA ligase IV (Lig4) reversed this acceleration of the DDR. Furthermore, the frequency of irradiation-induced apoptosis was decreased by TGF-β1 pretreatment in vivo, but this effect was abrogated by SB431542. These results collectively suggest that TGF-β1 could enhance cell survival by accelerating the DDR via Smad signaling and Lig4 expression. -- Highlights: •TGF-β1 pretreatment accelerates γ-radiation-induced DNA damage response. •TGF-β1-accelerated DNA damage response is dependent on Smad signaling and DNA Ligase IV. •TGF-β1 pretreatment protects epithelial cells from γ-radiation in vivo.« less

Sequence of events from the onset to the demise of the Last Interglacial: Evaluating strengths and limitations of chronologies used in climatic archives

NASA Astrophysics Data System (ADS)

Govin, A.; Capron, E.; Tzedakis, P. C.; Verheyden, S.; Ghaleb, B.; Hillaire-Marcel, C.; St-Onge, G.; Stoner, J. S.; Bassinot, F.; Bazin, L.; Blunier, T.; Combourieu-Nebout, N.; El Ouahabi, A.; Genty, D.; Gersonde, R.; Jimenez-Amat, P.; Landais, A.; Martrat, B.; Masson-Delmotte, V.; Parrenin, F.; Seidenkrantz, M.-S.; Veres, D.; Waelbroeck, C.; Zahn, R.

2015-12-01

The Last Interglacial (LIG) represents an invaluable case study to investigate the response of components of the Earth system to global warming. However, the scarcity of absolute age constraints in most archives leads to extensive use of various stratigraphic alignments to different reference chronologies. This feature sets limitations to the accuracy of the stratigraphic assignment of the climatic sequence of events across the globe during the LIG. Here, we review the strengths and limitations of the methods that are commonly used to date or develop chronologies in various climatic archives for the time span (∼140-100 ka) encompassing the penultimate deglaciation, the LIG and the glacial inception. Climatic hypotheses underlying record alignment strategies and the interpretation of tracers are explicitly described. Quantitative estimates of the associated absolute and relative age uncertainties are provided. Recommendations are subsequently formulated on how best to define absolute and relative chronologies. Future climato-stratigraphic alignments should provide (1) a clear statement of climate hypotheses involved, (2) a detailed understanding of environmental parameters controlling selected tracers and (3) a careful evaluation of the synchronicity of aligned paleoclimatic records. We underscore the need to (1) systematically report quantitative estimates of relative and absolute age uncertainties, (2) assess the coherence of chronologies when comparing different records, and (3) integrate these uncertainties in paleoclimatic interpretations and comparisons with climate simulations. Finally, we provide a sequence of major climatic events with associated age uncertainties for the period 140-105 ka, which should serve as a new benchmark to disentangle mechanisms of the Earth system's response to orbital forcing and evaluate transient climate simulations.

Analysis of the Functions of Recombination-Related Genes in the Generation of Large Chromosomal Deletions by Loop-Out Recombination in Aspergillus oryzae

PubMed Central

Ogawa, Masahiro; Koyama, Yasuji

2012-01-01

Loop-out-type recombination is a type of intrachromosomal recombination followed by the excision of a chromosomal region. The detailed mechanism underlying this recombination and the genes involved in loop-out recombination remain unknown. In the present study, we investigated the functions of ku70, ligD, rad52, rad54, and rdh54 in the construction of large chromosomal deletions via loop-out recombination and the effect of the position of the targeted chromosomal region on the efficiency of loop-out recombination in Aspergillus oryzae. The efficiency of generation of large chromosomal deletions in the near-telomeric region of chromosome 3, including the aflatoxin gene cluster, was compared with that in the near-centromeric region of chromosome 8, including the tannase gene. In the Δku70 and Δku70-rdh54 strains, only precise loop-out recombination occurred in the near-telomeric region. In contrast, in the ΔligD, Δku70-rad52, and Δku70-rad54 strains, unintended chromosomal deletions by illegitimate loop-out recombination occurred in the near-telomeric region. In addition, large chromosomal deletions via loop-out recombination were efficiently achieved in the near-telomeric region, but barely achieved in the near-centromeric region, in the Δku70 strain. Induction of DNA double-strand breaks by I-SceI endonuclease facilitated large chromosomal deletions in the near-centromeric region. These results indicate that ligD, rad52, and rad54 play a role in the generation of large chromosomal deletions via precise loop-out-type recombination in the near-telomeric region and that loop-out recombination between distant sites is restricted in the near-centromeric region by chromosomal structure. PMID:22286092

Last Interglacial climate and sea-level evolution from a coupled ice sheet-climate model

NASA Astrophysics Data System (ADS)

Goelzer, Heiko; Huybrechts, Philippe; Loutre, Marie-France; Fichefet, Thierry

2016-12-01

As the most recent warm period in Earth's history with a sea-level stand higher than present, the Last Interglacial (LIG, ˜ 130 to 115 kyr BP) is often considered a prime example to study the impact of a warmer climate on the two polar ice sheets remaining today. Here we simulate the Last Interglacial climate, ice sheet, and sea-level evolution with the Earth system model of intermediate complexity LOVECLIM v.1.3, which includes dynamic and fully coupled components representing the atmosphere, the ocean and sea ice, the terrestrial biosphere, and the Greenland and Antarctic ice sheets. In this setup, sea-level evolution and climate-ice sheet interactions are modelled in a consistent framework.Surface mass balance change governed by changes in surface meltwater runoff is the dominant forcing for the Greenland ice sheet, which shows a peak sea-level contribution of 1.4 m at 123 kyr BP in the reference experiment. Our results indicate that ice sheet-climate feedbacks play an important role to amplify climate and sea-level changes in the Northern Hemisphere. The sensitivity of the Greenland ice sheet to surface temperature changes considerably increases when interactive albedo changes are considered. Southern Hemisphere polar and sub-polar ocean warming is limited throughout the Last Interglacial, and surface and sub-shelf melting exerts only a minor control on the Antarctic sea-level contribution with a peak of 4.4 m at 125 kyr BP. Retreat of the Antarctic ice sheet at the onset of the LIG is mainly forced by rising sea level and to a lesser extent by reduced ice shelf viscosity as the surface temperature increases. Global sea level shows a peak of 5.3 m at 124.5 kyr BP, which includes a minor contribution of 0.35 m from oceanic thermal expansion. Neither the individual contributions nor the total modelled sea-level stand show fast multi-millennial timescale variations as indicated by some reconstructions.

Effects of warm-up on vertical jump performance and muscle electrical activity using half-squats at low and moderate intensity.

PubMed

Sotiropoulos, Konstantinos; Smilios, Ilias; Christou, Marios; Barzouka, Karolina; Spaias, Angelos; Douda, Helen; Tokmakidis, Savvas P

2010-01-01

The purpose of this study was to determine the effects of a specific warm-up using half-squats at low and moderate intensity on vertical jump performance and electromyographic activity of the thigh muscles. The subjects were 26 men who were divided into a low intensity group (LIG; n = 13) and a moderate intensity group (MIG; n = 13). The LIG performed a specific warm-up protocol that included the explosive execution of half-squats with loads 25 and 35% of the one repetition maximum (1RM) and the MIG with loads 45 and 65% of the 1RM. The two groups performed a countermovement jump (CMJ) before and three minutes after the specific warm-up protocols. During the concentric phase of the CMJ a linear encoder connected to an A/D converter interfaced to a PC with a software for data acquisition and analysis allowed the calculation of average mechanical power. The electromyographic (EMG) activity of the vastus lateralis (VL), vastus medialis (VM) and rectus femoris (RF) were recorded during the concentric phase of the jumps. The average quadriceps (Qc) activity (mean value of the VL, VM and RF) was also calculated. A two way ANOVA (protocols X time) with repeated measures on the second factor was used to analyze the data. Following the specific warm-up procedure both groups improved (p ≤ 0.05) CMJ performance and mechanical power by 3.5% and 6.3%, respectively, with no differences observed between the two groups. EMG activity of the Qc and VL increased (p ≤ 0.05) for both groups by 5.9% and 8.5%, respectively. It is concluded that the use of a specific warm-up that includes half-squats, performed explosively with low to moderate intensity, improves CMJ performance. This may be due to increased muscle activation as evaluated by the surface EMG. Key pointsThe inclusion of two sets of explosively performed half squats with low to moderate loads in the warm up procedure elicited an acute performance en-hancement.The performance was enhanced regardless of the load used in the warm-up.The performance enhancement is accompanied by a greater electromyographic activity of the knee extensors muscles.

Effects of Warm-Up on Vertical Jump Performance and Muscle Electrical Activity Using Half-Squats at Low and Moderate Intensity

PubMed Central

Sotiropoulos, Konstantinos; Smilios, Ilias; Christou, Marios; Barzouka, Karolina; Spaias, Angelos; Douda, Helen; Tokmakidis, Savvas p.

2010-01-01

The purpose of this study was to determine the effects of a specific warm-up using half-squats at low and moderate intensity on vertical jump performance and electromyographic activity of the thigh muscles. The subjects were 26 men who were divided into a low intensity group (LIG; n = 13) and a moderate intensity group (MIG; n = 13). The LIG performed a specific warm-up protocol that included the explosive execution of half-squats with loads 25 and 35% of the one repetition maximum (1RM) and the MIG with loads 45 and 65% of the 1RM. The two groups performed a countermovement jump (CMJ) before and three minutes after the specific warm-up protocols. During the concentric phase of the CMJ a linear encoder connected to an A/D converter interfaced to a PC with a software for data acquisition and analysis allowed the calculation of average mechanical power. The electromyographic (EMG) activity of the vastus lateralis (VL), vastus medialis (VM) and rectus femoris (RF) were recorded during the concentric phase of the jumps. The average quadriceps (Qc) activity (mean value of the VL, VM and RF) was also calculated. A two way ANOVA (protocols X time) with repeated measures on the second factor was used to analyze the data. Following the specific warm-up procedure both groups improved (p ≤ 0.05) CMJ performance and mechanical power by 3.5% and 6.3%, respectively, with no differences observed between the two groups. EMG activity of the Qc and VL increased (p ≤ 0.05) for both groups by 5.9% and 8.5%, respectively. It is concluded that the use of a specific warm-up that includes half-squats, performed explosively with low to moderate intensity, improves CMJ performance. This may be due to increased muscle activation as evaluated by the surface EMG. Key points The inclusion of two sets of explosively performed half squats with low to moderate loads in the warm up procedure elicited an acute performance en-hancement. The performance was enhanced regardless of the load used in the warm-up. The performance enhancement is accompanied by a greater electromyographic activity of the knee extensors muscles. PMID:24149703

CHARACTERIZATION OF FLAME-SYNTHESIZED FE, CO, OR MN-DOPED TITANIA NANOSTRUCTURED PARTICLES

EPA Science Inventory

The flame-synthesized catalysts have higher surface areas than commercial-grade titania and are composed of nanometer-sized primary particles with low internal porosity. Preliminary studies suggest that flame-synthesized iron-doped titania may be photoactivated in the visible lig...

Floodplain restoration increases hyporheic flow in the Yakima River Watershed, Washington

EPA Science Inventory

Hyporheic exchange between a river channel and its floodplain region assists in mediating processes such as nutrient removal and temperature regulation. Floodplain restoration in the form of levee setbacks are often carried out to improve the hyporheic exchange. In this study Lig...

Viscoelastic properties of kenaf bast fiber in relation to stem age

USDA-ARS?s Scientific Manuscript database

Natural fibers traditionally used for cordage are proving valuable for advanced industrial applications due in part to beneficial physical and chemical properties, but also because they are a renewable and biodegradable resource. Kenaf (Hibiscus cannabinus L., Malvaceae) produces high yields of lig...

Distinct photoresponse in graphene induced by laser irradiation and interfacial gating.

NASA Astrophysics Data System (ADS)

Wang, Wenhui; Guo, Xitao; Nan, Haiyan; Ni, Zhenhua; Spectroscopy; Optoelectronics Group Team

Graphene-based photodetectors have recently received much attention due to its unique optical and electronic properties. The photoresponse modulation plays a crucial role in the study of photocurrent generation mechanism and optoelectronic applications. Here, the tunable p-p +-p junctions of graphene were fabricated through simple laser irradiation process. Distinct photoresponse was observed at the graphene (G)-laser irradiation graphene (LIG) junction. Detailed investigation suggests that the photo-thermoelectric effect, instead of the photovoltaic effect, dominates the photocurrent generation at the G-LIG junction. On the other hand, the localized interface states, existing at the silicon dioxide/lightly doped Si interface, would induce an interfacial gating mechanism, which will enhance the photoresponsivity to 1000 A/W. More important, the photoresponse time of our device has been pushed to 400ns. The current device structure does not need a complicated fabrication process and is fully compatible with silicon technology. This work will open up a route to graphene-based high-performance optoelectronic devices. This work was supported by Southeast University.

A study on operative findings and pathogenic factors in ulnar neuropathy at the elbow.

PubMed

Kojima, T; Kurihara, K; Nagano, T

1979-01-01

A study was made of operative findings obtained in 44 cases of ulnar nerve neuropathy at the elbow in an attempt to help elucidate the pathogenetic factors for the condition. Distinction must be made between Lig. epitrochleo-anconeum or a ligament-like thickening at the same site and the tendinous arch of M. flexor carpi ulnaris. These 2 sites constitute the entrapment points for the condition. A thick tendinous arch, Lig. epitrochleo-anconeum of M. anconeus epitrochlearis deters the ulnar nerve from being mobile, thereby contributing to the development of neuropathy with trauma acting as a precipitating factor. Dislocation of the ulnar nerve cannot be considered a factor of major etiologic significance. An important part is played by the tendinous arch in the pathogenesis of neuropathy, regardless of whether it is in association with ganglion, osteochondromatosis or osteoarthritis. In surgery for ulnar neuropathy decompression of the nerve is of primary necessity. Division of the tendinous arch is mandatory. Medial epicondylectomy may be added as required.

p73 coordinates with Δ133p53 to promote DNA double-strand break repair.

PubMed

Gong, Hongjian; Zhang, Yuxi; Jiang, Kunpeng; Ye, Shengfan; Chen, Shuming; Zhang, Qinghe; Peng, Jinrong; Chen, Jun

2018-03-06

Tumour repressor p53 isoform Δ133p53 is a target gene of p53 and an antagonist of p53-mediated apoptotic activity. We recently demonstrated that Δ133p53 promotes DNA double-strand break (DSB) repair by upregulating transcription of the repair genes RAD51, LIG4 and RAD52 in a p53-independent manner. However, Δ133p53 lacks the transactivation domain of full-length p53, and the mechanism by which it exerts transcriptional activity independently of full-length p53 remains unclear. In this report, we describe the accumulation of high levels of both Δ133p53 and p73 (a p53 family member) at 24 h post γ-irradiation (hpi). Δ133p53 can form a complex with p73 upon γ-irradiation. The co-expression of Δ133p53 and p73, but not either protein alone, can significantly promote DNA DSB repair mechanisms, including homologous recombination (HR), non-homologous end joining (NHEJ) and single-strand annealing (SSA). p73 and Δ133p53 act synergistically to promote the expression of RAD51, LIG4 and RAD52 by joining together to bind to region containing a Δ133p53-responsive element (RE) and a p73-RE in the promoters of all three repair genes. In addition to its accumulation at 24 hpi, p73 protein expression also peaks at 4 hpi. The depletion of p73 not only reduces early-stage apoptotic frequency (4-6 hpi), but also significantly increases later-stage DNA DSB accumulation (48 hpi), leading to cell cycle arrest in the G2 phase and, ultimately, cell senescence. In summary, the apoptotic regulator p73 also coordinates with Δ133p53 to promote DNA DSB repair, and the loss of function of p73 in DNA DSB repair may underlie spontaneous and carcinogen-induced tumorigenesis in p73 knockout mice.

Soil, water, and greenhouse-gas impacts of alternative biomass cropping systems

USDA-ARS?s Scientific Manuscript database

Through the 2008 Energy Independence and Security Act and other state and federal mandates, the U.S. is embarking on an aggressive agenda to reduce dependency on fossil fuels. While grain-derived ethanol will be used to largely meet initial renewable fuels targets, advanced biofuels derived from lig...

Molecular and physiological mechanisms of plant tolerance to toxic metals

USDA-ARS?s Scientific Manuscript database

Plants have evolved a myriad of adaptive mechanisms based on a number of genes to deal with the different toxic metals they encounter in the soils worldwide. These genes encode a range of different metal and organic compound transporters and enzyme pathways for the synthesis of metal detoxifying lig...

The impact of the conversion of incandescent bulbs to the LED light source in traffic signals in Houston : a step toward sustainable control devices.

DOT National Transportation Integrated Search

2015-06-01

With the slowing of the American economy since 2008, it has become imperative that municipalities : identify areas in which costs can be reduced while still providing needed services to its constituents. The : use of traffic signals equipped with lig...

Literature Review of Spherical Resorcinol-Formaldehyde for Cesium Ion Exchange

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, Garrett N.

2014-09-30

The current report summarizes work performed throughout the scientific community and DOE complex as reported in the open literature and DOE-sponsored reports to evaluate the Cs+ ion exchange (CIX) characteristics of SRF resin. King (2007) completed a similar literature review in support of material selection for the Small Column Ion Exchange (SCIX) project. Josephson et al. (2010) and Sams et al. (2009) provided a similar brief review of SRF CIX for the near-tank Cs+ removal (NTCR) project. Thorson (2008a) documented the basis for recommending SRF over SuperLigTM 644 as the primary CIX resin in the WTP. The current review expandsmore » on previous work, summarizes additional work completed to date, and provides a broad view of the literature without focusing on a specific column system. Although the focus of the current review is the SRF resin, many cited references include multiple materials such as the non-spherical GGRF and SuperLigTM 644 organic resins and crystalline silicotitanate (CST) IONSIVTM IE-911, a non-elutable inorganic material. This report summarizes relevant information provided in the literature.« less

Genome-Wide Association Study Reveals the Genetic Basis of Stalk Cell Wall Components in Maize

PubMed Central

Hu, Xiaojiao; Liu, Zhifang; Wu, Yujin; Huang, Changling

2016-01-01

Lignin, cellulose and hemicellulose are the three main components of the plant cell wall and can impact stalk quality by affecting cell wall structure and strength. In this study, we evaluated the lignin (LIG), cellulose (CEL) and hemicellulose (HC) contents in maize using an association mapping panel that included 368 inbred lines in seven environments. A genome-wide association study using approximately 0.56 million SNPs with a minor allele frequency of 0.05 identified 22, 18 and 24 loci significantly associated with LIG, CEL and HC at P < 1.0×10−4, respectively. The allelic variation of each significant association contributed 4 to 7% of the phenotypic variation. Candidate genes identified by GWAS mainly encode enzymes involved in cell wall metabolism, transcription factors, protein kinase and protein related to other biological processes. Among the association signals, six candidate genes had pleiotropic effects on lignin and cellulose content. These results provide valuable information for better understanding the genetic basis of stalk cell wall components in maize. PMID:27479588

Alternative end-joining pathway(s): bricolage at DNA breaks.

PubMed

Frit, Philippe; Barboule, Nadia; Yuan, Ying; Gomez, Dennis; Calsou, Patrick

2014-05-01

To cope with DNA double strand break (DSB) genotoxicity, cells have evolved two main repair pathways: homologous recombination which uses homologous DNA sequences as repair templates, and non-homologous Ku-dependent end-joining involving direct sealing of DSB ends by DNA ligase IV (Lig4). During the last two decades a third player most commonly named alternative end-joining (A-EJ) has emerged, which is defined as any Ku- or Lig4-independent end-joining process. A-EJ increasingly appears as a highly error-prone bricolage on DSBs and despite expanding exploration, it still escapes full characterization. In the present review, we discuss the mechanism and regulation of A-EJ as well as its biological relevance under physiological and pathological situations, with a particular emphasis on chromosomal instability and cancer. Whether or not it is a genuine DSB repair pathway, A-EJ is emerging as an important cellular process and understanding A-EJ will certainly be a major challenge for the coming years. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Use of essential gene, encoding prophobilinogen deaminase from extreme psychrophilic Colwellia sp. C1, to generate temperature-sensitive strain of Francisella novicida.

PubMed

Pankowski, J A

2016-08-01

Previously, several essential genes from psychrophilic bacteria have been substituted for their homologues in mesophilic bacterial pathogens to make the latter temperature sensitive. It has been noted that an essential ligA gene from an extreme psychrophile, Colwellia sp. C1, yielded a gene product that is inactivated at 27°C, the lowest that has been observed for any psychrophilic enzyme, and hypothesized that other essential proteins of that strain would also have low inactivation temperatures. This work describes the partial sequencing of the genome of Colwellia sp. C1 strain and the identification of 24 open reading frames encoding homologues of highly conserved bacterial essential genes. The gene encoding porphobilinogen deaminase (hemC), which is involved in the pathway of haem synthesis, has been tested for its ability to convert Francisella novicida into a temperature-sensitive strain. The hybrid strain carrying the C1-derived hemC gene exhibited a temperature-sensitive phenotype with a restrictive temperature of 36°C. These results support the conclusion that Colwellia sp. C1 is a rich source of heat-labile enzymes. The issue of biosafety is often raised when it comes to work with pathogenic organisms. The main concern is caused by the risk of researchers being exposed to infectious doses of dangerous microbes. This paper analyses essential genes identified in partial genomic sequence of the psychrophilic bacterium Collwelia sp. C1. These sequences can be used as a mean of generating temperature-sensitive strains of pathogenic bacteria. Such strains are incapable of surviving at the temperature of human body. This means they could be applied as vaccines or for safer work with dangerous organisms. © 2016 The Society for Applied Microbiology.

Highly Precise and Developmentally Programmed Genome Assembly in Paramecium Requires Ligase IV–Dependent End Joining

PubMed Central

Marmignon, Antoine; Ku, Michael; Silve, Aude; Meyer, Eric; Forney, James D.; Malinsky, Sophie; Bétermier, Mireille

2011-01-01

During the sexual cycle of the ciliate Paramecium, assembly of the somatic genome includes the precise excision of tens of thousands of short, non-coding germline sequences (Internal Eliminated Sequences or IESs), each one flanked by two TA dinucleotides. It has been reported previously that these genome rearrangements are initiated by the introduction of developmentally programmed DNA double-strand breaks (DSBs), which depend on the domesticated transposase PiggyMac. These DSBs all exhibit a characteristic geometry, with 4-base 5′ overhangs centered on the conserved TA, and may readily align and undergo ligation with minimal processing. However, the molecular steps and actors involved in the final and precise assembly of somatic genes have remained unknown. We demonstrate here that Ligase IV and Xrcc4p, core components of the non-homologous end-joining pathway (NHEJ), are required both for the repair of IES excision sites and for the circularization of excised IESs. The transcription of LIG4 and XRCC4 is induced early during the sexual cycle and a Lig4p-GFP fusion protein accumulates in the developing somatic nucleus by the time IES excision takes place. RNAi–mediated silencing of either gene results in the persistence of free broken DNA ends, apparently protected against extensive resection. At the nucleotide level, controlled removal of the 5′-terminal nucleotide occurs normally in LIG4-silenced cells, while nucleotide addition to the 3′ ends of the breaks is blocked, together with the final joining step, indicative of a coupling between NHEJ polymerase and ligase activities. Taken together, our data indicate that IES excision is a “cut-and-close” mechanism, which involves the introduction of initiating double-strand cleavages at both ends of each IES, followed by DSB repair via highly precise end joining. This work broadens our current view on how the cellular NHEJ pathway has cooperated with domesticated transposases for the emergence of new mechanisms involved in genome dynamics. PMID:21533177

Highly precise and developmentally programmed genome assembly in Paramecium requires ligase IV-dependent end joining.

PubMed

Kapusta, Aurélie; Matsuda, Atsushi; Marmignon, Antoine; Ku, Michael; Silve, Aude; Meyer, Eric; Forney, James D; Malinsky, Sophie; Bétermier, Mireille

2011-04-01

During the sexual cycle of the ciliate Paramecium, assembly of the somatic genome includes the precise excision of tens of thousands of short, non-coding germline sequences (Internal Eliminated Sequences or IESs), each one flanked by two TA dinucleotides. It has been reported previously that these genome rearrangements are initiated by the introduction of developmentally programmed DNA double-strand breaks (DSBs), which depend on the domesticated transposase PiggyMac. These DSBs all exhibit a characteristic geometry, with 4-base 5' overhangs centered on the conserved TA, and may readily align and undergo ligation with minimal processing. However, the molecular steps and actors involved in the final and precise assembly of somatic genes have remained unknown. We demonstrate here that Ligase IV and Xrcc4p, core components of the non-homologous end-joining pathway (NHEJ), are required both for the repair of IES excision sites and for the circularization of excised IESs. The transcription of LIG4 and XRCC4 is induced early during the sexual cycle and a Lig4p-GFP fusion protein accumulates in the developing somatic nucleus by the time IES excision takes place. RNAi-mediated silencing of either gene results in the persistence of free broken DNA ends, apparently protected against extensive resection. At the nucleotide level, controlled removal of the 5'-terminal nucleotide occurs normally in LIG4-silenced cells, while nucleotide addition to the 3' ends of the breaks is blocked, together with the final joining step, indicative of a coupling between NHEJ polymerase and ligase activities. Taken together, our data indicate that IES excision is a "cut-and-close" mechanism, which involves the introduction of initiating double-strand cleavages at both ends of each IES, followed by DSB repair via highly precise end joining. This work broadens our current view on how the cellular NHEJ pathway has cooperated with domesticated transposases for the emergence of new mechanisms involved in genome dynamics.

Genetic and ecological insights into glacial refugia of walnut (Juglans regia L.)

PubMed Central

Aradhya, Mallikarjuna; Ibrahimov, Zakir; Toktoraliev, Biimyrza; Maghradze, David; Musayev, Mirza; Bobokashvili, Zviadi; Preece, John E.

2017-01-01

The distribution and survival of trees during the last glacial maximum (LGM) has been of interest to paleoecologists, biogeographers, and geneticists. Ecological niche models that associate species occurrence and abundance with climatic variables are widely used to gain ecological and evolutionary insights and to predict species distributions over space and time. The present study deals with the glacial history of walnut to address questions related to past distributions through genetic analysis and ecological modeling of the present, LGM and Last Interglacial (LIG) periods. A maximum entropy method was used to project the current walnut distribution model on to the LGM (21–18 kyr BP) and LIG (130–116 kyr BP) climatic conditions. Model tuning identified the walnut data set filtered at 10 km spatial resolution as the best for modeling the current distribution and to hindcast past (LGM and LIG) distributions of walnut. The current distribution model predicted southern Caucasus, parts of West and Central Asia extending into South Asia encompassing northern Afghanistan, Pakistan, northwestern Himalayan region, and southwestern Tibet, as the favorable climatic niche matching the modern distribution of walnut. The hindcast of distributions suggested the occurrence of walnut during LGM was somewhat limited to southern latitudes from southern Caucasus, Central and South Asian regions extending into southwestern Tibet, northeastern India, Himalayan region of Sikkim and Bhutan, and southeastern China. Both CCSM and MIROC projections overlapped, except that MIROC projected a significant presence of walnut in the Balkan Peninsula during the LGM. In contrast, genetic analysis of the current walnut distribution suggested a much narrower area in northern Pakistan and the surrounding areas of Afghanistan, northwestern India, and southern Tajikistan as a plausible hotspot of diversity where walnut may have survived glaciations. Overall, the findings suggest that walnut perhaps survived the last glaciations in several refugia across a wide geographic area between 30° and 45° North latitude. However, humans probably played a significant role in the recent history and modern distribution of walnut. PMID:29023476

Uterine blood flow in sows: effects of pregnancy stage and litter size.

PubMed

Père, M C; Etienne, M

2000-01-01

Female pigs were assigned to three groups at 94 days of age: a control group (CTR), a group undergoing the ligation and severing of the left oviduct (LIG), and a group undergoing right hysteroovariectomy (HHO). They were inseminated at 307 days of age. At 35 days of pregnancy, an ultrasonic transit time flow probe was implanted around the middle artery of one uterine horn in 33 sows and uterine blood flow was measured during thirteen 24-h periods between 44 and 111 days. Despite large differences in ovulation rate per uterine horn (4.8, 8.3 and 16.9 in the LIG, CTR and HHO groups, respectively), variation of litter size was considerably reduced with advancement of pregnancy (3.0, 6.6 and 10.8 foetuses per uterine horn at 35 days, and 3.0, 5.8 and 4.9 at 112 days (slaughter), respectively). Uterine blood flow increased linearly during pregnancy. It was lower in the LIG sows (0.82 to 1.74 L x min(-1) x horn(-1) from 44 to 111 days) than in the CTR and HHO sows (1.22 to 2.84 and 1.09 to 2.63 L x min(-1) x horn(1), respectively). It was more closely related to litter weight than to litter size and amounted to 0.42 L x min(-1) x kg foetus(-1) at 111 days. Uterine blood flow per foetus decreased when litter size increased. It increased from 0.31 to 0.72, 0.26 to 0.60 and 0.20 to 0.43 L x min(-1) x foetus(-1) from 44 to 111 days when there were 2 to 3, 4 to 5, and 6 to 8 foetuses in the uterine horn, respectively. This explains why piglets from large litters are lighter at birth.

Genetic and ecological insights into glacial refugia of walnut (Juglans regia L.).

PubMed

Aradhya, Mallikarjuna; Velasco, Dianne; Ibrahimov, Zakir; Toktoraliev, Biimyrza; Maghradze, David; Musayev, Mirza; Bobokashvili, Zviadi; Preece, John E

2017-01-01

The distribution and survival of trees during the last glacial maximum (LGM) has been of interest to paleoecologists, biogeographers, and geneticists. Ecological niche models that associate species occurrence and abundance with climatic variables are widely used to gain ecological and evolutionary insights and to predict species distributions over space and time. The present study deals with the glacial history of walnut to address questions related to past distributions through genetic analysis and ecological modeling of the present, LGM and Last Interglacial (LIG) periods. A maximum entropy method was used to project the current walnut distribution model on to the LGM (21-18 kyr BP) and LIG (130-116 kyr BP) climatic conditions. Model tuning identified the walnut data set filtered at 10 km spatial resolution as the best for modeling the current distribution and to hindcast past (LGM and LIG) distributions of walnut. The current distribution model predicted southern Caucasus, parts of West and Central Asia extending into South Asia encompassing northern Afghanistan, Pakistan, northwestern Himalayan region, and southwestern Tibet, as the favorable climatic niche matching the modern distribution of walnut. The hindcast of distributions suggested the occurrence of walnut during LGM was somewhat limited to southern latitudes from southern Caucasus, Central and South Asian regions extending into southwestern Tibet, northeastern India, Himalayan region of Sikkim and Bhutan, and southeastern China. Both CCSM and MIROC projections overlapped, except that MIROC projected a significant presence of walnut in the Balkan Peninsula during the LGM. In contrast, genetic analysis of the current walnut distribution suggested a much narrower area in northern Pakistan and the surrounding areas of Afghanistan, northwestern India, and southern Tajikistan as a plausible hotspot of diversity where walnut may have survived glaciations. Overall, the findings suggest that walnut perhaps survived the last glaciations in several refugia across a wide geographic area between 30° and 45° North latitude. However, humans probably played a significant role in the recent history and modern distribution of walnut.

The PMIP4 contribution to CMIP6 - Part 1: Overview and over-arching analysis plan

NASA Astrophysics Data System (ADS)

Kageyama, Masa; Braconnot, Pascale; Harrison, Sandy P.; Haywood, Alan M.; Jungclaus, Johann H.; Otto-Bliesner, Bette L.; Peterschmitt, Jean-Yves; Abe-Ouchi, Ayako; Albani, Samuel; Bartlein, Patrick J.; Brierley, Chris; Crucifix, Michel; Dolan, Aisling; Fernandez-Donado, Laura; Fischer, Hubertus; Hopcroft, Peter O.; Ivanovic, Ruza F.; Lambert, Fabrice; Lunt, Daniel J.; Mahowald, Natalie M.; Peltier, W. Richard; Phipps, Steven J.; Roche, Didier M.; Schmidt, Gavin A.; Tarasov, Lev; Valdes, Paul J.; Zhang, Qiong; Zhou, Tianjun

2018-03-01

This paper is the first of a series of four GMD papers on the PMIP4-CMIP6 experiments. Part 2 (Otto-Bliesner et al., 2017) gives details about the two PMIP4-CMIP6 interglacial experiments, Part 3 (Jungclaus et al., 2017) about the last millennium experiment, and Part 4 (Kageyama et al., 2017) about the Last Glacial Maximum experiment. The mid-Pliocene Warm Period experiment is part of the Pliocene Model Intercomparison Project (PlioMIP) - Phase 2, detailed in Haywood et al. (2016).The goal of the Paleoclimate Modelling Intercomparison Project (PMIP) is to understand the response of the climate system to different climate forcings for documented climatic states very different from the present and historical climates. Through comparison with observations of the environmental impact of these climate changes, or with climate reconstructions based on physical, chemical, or biological records, PMIP also addresses the issue of how well state-of-the-art numerical models simulate climate change. Climate models are usually developed using the present and historical climates as references, but climate projections show that future climates will lie well outside these conditions. Palaeoclimates very different from these reference states therefore provide stringent tests for state-of-the-art models and a way to assess whether their sensitivity to forcings is compatible with palaeoclimatic evidence. Simulations of five different periods have been designed to address the objectives of the sixth phase of the Coupled Model Intercomparison Project (CMIP6): the millennium prior to the industrial epoch (CMIP6 name: past1000); the mid-Holocene, 6000 years ago (midHolocene); the Last Glacial Maximum, 21 000 years ago (lgm); the Last Interglacial, 127 000 years ago (lig127k); and the mid-Pliocene Warm Period, 3.2 million years ago (midPliocene-eoi400). These climatic periods are well documented by palaeoclimatic and palaeoenvironmental records, with climate and environmental changes relevant for the study and projection of future climate changes. This paper describes the motivation for the choice of these periods and the design of the numerical experiments and database requests, with a focus on their novel features compared to the experiments performed in previous phases of PMIP and CMIP. It also outlines the analysis plan that takes advantage of the comparisons of the results across periods and across CMIP6 in collaboration with other MIPs.

Suppression of cucumber powdery mildew by UV-B is affected by background light quality

USDA-ARS?s Scientific Manuscript database

Brief (5-10 min) exposure to UV-B radiation (280-300 nm) suppressed powdery mildew (Podosphaera xanthii) on Cucumis sativus. The effect was enhanced by red light (600-660 nm), but offset by blue light (420-500 nm) and UV-A (300-420 nm). Compared to untreated controls, 2 h red light from specific lig...

Neuronal targeting, internalization, and biological activity of a recombinant atoxic derivative of botulinum neurotoxin A

USDA-ARS?s Scientific Manuscript database

Non-toxic derivatives of Botulinum neurotoxin A (BoNT/A) have potential use as neuron-targeting delivery vehicles, and as reagents to study intracellular trafficking. We have designed and expressed an atoxic derivative of BoNT/A (BoNT/A ad) as a full-length 150kDa molecule consisting of a 50 kDa lig...

Space-Filling Supercapacitor Carpets: Highly scalable fractal architecture for energy storage

NASA Astrophysics Data System (ADS)

Tiliakos, Athanasios; Trefilov, Alexandra M. I.; Tanasǎ, Eugenia; Balan, Adriana; Stamatin, Ioan

2018-04-01

Revamping ground-breaking ideas from fractal geometry, we propose an alternative micro-supercapacitor configuration realized by laser-induced graphene (LIG) foams produced via laser pyrolysis of inexpensive commercial polymers. The Space-Filling Supercapacitor Carpet (SFSC) architecture introduces the concept of nested electrodes based on the pre-fractal Peano space-filling curve, arranged in a symmetrical equilateral setup that incorporates multiple parallel capacitor cells sharing common electrodes for maximum efficiency and optimal length-to-area distribution. We elucidate on the theoretical foundations of the SFSC architecture, and we introduce innovations (high-resolution vector-mode printing) in the LIG method that allow for the realization of flexible and scalable devices based on low iterations of the Peano algorithm. SFSCs exhibit distributed capacitance properties, leading to capacitance, energy, and power ratings proportional to the number of nested electrodes (up to 4.3 mF, 0.4 μWh, and 0.2 mW for the largest tested model of low iteration using aqueous electrolytes), with competitively high energy and power densities. This can pave the road for full scalability in energy storage, reaching beyond the scale of micro-supercapacitors for incorporating into larger and more demanding applications.

TRF2/RAP1 and DNA–PK mediate a double protection against joining at telomeric ends

PubMed Central

Bombarde, Oriane; Boby, Céline; Gomez, Dennis; Frit, Philippe; Giraud-Panis, Marie-Josèphe; Gilson, Eric; Salles, Bernard; Calsou, Patrick

2010-01-01

DNA-dependent protein kinase (DNA-PK) is a double-strand breaks repair complex, the subunits of which (KU and DNA-PKcs) are paradoxically present at mammalian telomeres. Telomere fusion has been reported in cells lacking these proteins, raising two questions: how is DNA–PK prevented from initiating classical ligase IV (LIG4)-dependent non-homologous end-joining (C-NHEJ) at telomeres and how is the backup end-joining (EJ) activity (B-NHEJ) that operates at telomeres under conditions of C-NHEJ deficiency controlled? To address these questions, we have investigated EJ using plasmid substrates bearing double-stranded telomeric tracks and human cell extracts with variable C-NHEJ or B-NHEJ activity. We found that (1) TRF2/RAP1 prevents C-NHEJ-mediated end fusion at the initial DNA–PK end binding and activation step and (2) DNA–PK counteracts a potent LIG4-independent EJ mechanism. Thus, telomeres are protected against EJ by a lock with two bolts. These results account for observations with mammalian models and underline the importance of alternative non-classical EJ pathways for telomere fusions in cells. PMID:20407424

Overcoming a hemihedral twinning problem in tetrahydrofolate-dependent O -demethylase crystals by the microseeding method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harada, Ayaka; Sato, Yukari; Kamimura, Naofumi

2016-11-30

A tetrahydrofolate-dependentO-demethylase, LigM, fromSphingobiumsp. SYK-6 was crystallized by the hanging-drop vapour-diffusion method. However, the obtainedP3 121 orP3 221 crystals, which diffracted to 2.5–3.3 Å resolution, were hemihedrally twinned. To overcome the twinning problem, microseeding usingP3 121/P3 221 crystals as microseeds was performed with optimization of the reservoir conditions. As a result, another crystal form was obtained. The newly obtained crystal diffracted to 2.5–3.0 Å resolution and belonged to space groupP2 12 12, with unit-cell parametersa= 102.0,b= 117.3,c= 128.1 Å. TheP2 12 12 crystals diffracted to better than 2.0 Å resolution after optimizing the cryoconditions. Phasing using the single anomalous diffractionmore » method was successful at 3.0 Å resolution with a Pt-derivative crystal. This experience suggested that microseeding is an effective method to overcome the twinning problem, even when twinned crystals are utilized as microseeds.« less

Overcoming a hemihedral twinning problem in tetrahydrofolate-dependent O -demethylase crystals by the microseeding method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harada, Ayaka; Sato, Yukari; Kamimura, Naofumi

2016-11-30

A tetrahydrofolate-dependentO-demethylase, LigM, from Sphingobiumsp. SYK-6 was crystallized by the hanging-drop vapour-diffusion method. However, the obtained P3 121 orP3 221 crystals, which diffracted to 2.5–3.3 Å resolution, were hemihedrally twinned. To overcome the twinning problem, microseeding using P3 121/P3 2 21 crystals as microseeds was performed with optimization of the reservoir conditions. As a result, another crystal form was obtained. The newly obtained crystal diffracted to 2.5–3.0 Å resolution and belonged to space group P2 12 12, with unit-cell parametersa= 102.0,b= 117.3,c = 128.1 Å. The P2 12 12 crystals diffracted to better than 2.0 Å resolution after optimizing themore » cryoconditions. Phasing using the single anomalous diffraction method was successful at 3.0 Å resolution with a Pt-derivative crystal. This experience suggested that microseeding is an effective method to overcome the twinning problem, even when twinned crystals are utilized as microseeds.« less

Genetic Determinants for Promoter Hypermethylation in the Lungs of Smokers: A Candidate Gene-Based Study

PubMed Central

Leng, Shuguang; Stidley, Christine A.; Liu, Yushi; Edlund, Christopher K.; Willink, Randall P.; Han, Younghun; Landi, Maria Teresa; Thun, Michael; Picchi, Maria A.; Bruse, Shannon E.; Crowell, Richard E.; Van Den Berg, David; Caporaso, Neil E.; Amos, Christopher I.; Siegfried, Jill M.; Tesfaigzi, Yohannes; Gilliland, Frank D.; Belinsky, Steven A.

2011-01-01

The detection of tumor suppressor gene promoter methylation in sputum-derived exfoliated cells predicts early lung cancer. Here we identified genetic determinants for this epigenetic process and examined their biological effects on gene regulation. A two-stage approach involving discovery and replication was employed to assess the association between promoter hypermethylation of a 12-gene panel and common variation in 40 genes involved in carcinogen metabolism, regulation of methylation, and DNA damage response in members of the Lovelace Smokers Cohort (n=1434). Molecular validation of three identified variants was conducted using primary bronchial epithelial cells. Association of study-wide significance (P<8.2×10−5) was identified for rs1641511, rs3730859, and rs1883264 in TP53, LIG1, and BIK, respectively. These SNPs were significantly associated with altered expression of the corresponding genes in primary bronchial epithelial cells. In addition, rs3730859 in LIG1 was also moderately associated with increased risk for lung cancer among Caucasian smokers. Together, our findings suggest that genetic variation in DNA replication and apoptosis pathways impacts the propensity for gene promoter hypermethylation in the aerodigestive tract of smokers. The incorporation of genetic biomarkers for gene promoter hypermethylation with clinical and somatic markers may improve risk assessment models for lung cancer. PMID:22139380

Training, Muscle Fatigue, and Stress Fractures

DTIC Science & Technology

1988-07-15

fractures in the lower appendicular skeleton of new recruits. During peacetime, stress fractures are by far the most co~m~n physical injury in the...research program is to study the etiology of the stress fracture lesion, and isolate any aspects of a physical regime which may exacerbate this...34 of remodelLig, to use the model to identify those areas of the cortex at greatest risk of failure, and the activities which accelerate the deleterious

Four Pillars of Service-Oriented Architecture

DTIC Science & Technology

2007-09-01

ic A lig n m e n t Figure 1: Pillars of SOA-Based Systems Development Service -Oriented Architectures 12 CROSSTALK The Journal of Defense Software ...et al. “On the Business Value and Technical Challenges of Adopting Web Services .” Journal of Software Maintenance and Evolution 16 (2004): 16, 31-50...10 CROSSTALK The Journal of Defense Software Engineering September 2007 Acornerstone of DoD policy forfuture software and systems policy is the

Temperature-Sensitive Salmonella enterica Serovar Enteritidis PT13a Expressing Essential Proteins of Psychrophilic Bacteria.

PubMed

Duplantis, Barry N; Puckett, Stephanie M; Rosey, Everett L; Ameiss, Keith A; Hartman, Angela D; Pearce, Stephanie C; Nano, Francis E

2015-10-01

Synthetic genes based on deduced amino acid sequences of the NAD-dependent DNA ligase (ligA) and CTP synthetase (pyrG) of psychrophilic bacteria were substituted for their native homologues in the genome of Salmonella enterica serovar Enteritidis phage type 13a (PT13a). The resulting strains were rendered temperature sensitive (TS) and did not revert to temperature resistance at a detectable level. At permissive temperatures, TS strains grew like the parental strain in broth medium and in macrophage-like cells, but their growth was slowed or stopped when they were shifted to a restrictive temperature. When injected into BALB/c mice at the base of the tail, representing a cool site of the body, the strains with restrictive temperatures of 37, 38.5, and 39°C persisted for less than 1 day, 4 to 7 days, and 20 to 28 days, respectively. The wild-type strain persisted at the site of inoculation for at least 28 days. The wild-type strain, but not the TS strains, was also found in spleen-plus-liver homogenates within 1 day of inoculation of the tail and was detectable in these organs for at least 28 days. Intramuscular vaccination of White Leghorn chickens with the PT13a strain carrying the psychrophilic pyrG gene provided some protection against colonization of the reproductive tract and induced an anti-S. enterica antibody response. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Temperature-Sensitive Salmonella enterica Serovar Enteritidis PT13a Expressing Essential Proteins of Psychrophilic Bacteria

PubMed Central

Duplantis, Barry N.; Puckett, Stephanie M.; Rosey, Everett L.; Ameiss, Keith A.; Hartman, Angela D.; Pearce, Stephanie C.

2015-01-01

Synthetic genes based on deduced amino acid sequences of the NAD-dependent DNA ligase (ligA) and CTP synthetase (pyrG) of psychrophilic bacteria were substituted for their native homologues in the genome of Salmonella enterica serovar Enteritidis phage type 13a (PT13a). The resulting strains were rendered temperature sensitive (TS) and did not revert to temperature resistance at a detectable level. At permissive temperatures, TS strains grew like the parental strain in broth medium and in macrophage-like cells, but their growth was slowed or stopped when they were shifted to a restrictive temperature. When injected into BALB/c mice at the base of the tail, representing a cool site of the body, the strains with restrictive temperatures of 37, 38.5, and 39°C persisted for less than 1 day, 4 to 7 days, and 20 to 28 days, respectively. The wild-type strain persisted at the site of inoculation for at least 28 days. The wild-type strain, but not the TS strains, was also found in spleen-plus-liver homogenates within 1 day of inoculation of the tail and was detectable in these organs for at least 28 days. Intramuscular vaccination of White Leghorn chickens with the PT13a strain carrying the psychrophilic pyrG gene provided some protection against colonization of the reproductive tract and induced an anti-S. enterica antibody response. PMID:26187965

p53 isoform Δ113p53/Δ133p53 promotes DNA double-strand break repair to protect cell from death and senescence in response to DNA damage.

PubMed

Gong, Lu; Gong, Hongjian; Pan, Xiao; Chang, Changqing; Ou, Zhao; Ye, Shengfan; Yin, Le; Yang, Lina; Tao, Ting; Zhang, Zhenhai; Liu, Cong; Lane, David P; Peng, Jinrong; Chen, Jun

2015-03-01

The inhibitory role of p53 in DNA double-strand break (DSB) repair seems contradictory to its tumor-suppressing property. The p53 isoform Δ113p53/Δ133p53 is a p53 target gene that antagonizes p53 apoptotic activity. However, information on its functions in DNA damage repair is lacking. Here we report that Δ113p53 expression is strongly induced by γ-irradiation, but not by UV-irradiation or heat shock treatment. Strikingly, Δ113p53 promotes DNA DSB repair pathways, including homologous recombination, non-homologous end joining and single-strand annealing. To study the biological significance of Δ113p53 in promoting DNA DSB repair, we generated a zebrafish Δ113p53(M/M) mutant via the transcription activator-like effector nuclease technique and found that the mutant is more sensitive to γ-irradiation. The human ortholog, Δ133p53, is also only induced by γ-irradiation and functions to promote DNA DSB repair. Δ133p53-knockdown cells were arrested at the G2 phase at the later stage in response to γ-irradiation due to a high level of unrepaired DNA DSBs, which finally led to cell senescence. Furthermore, Δ113p53/Δ133p53 promotes DNA DSB repair via upregulating the transcription of repair genes rad51, lig4 and rad52 by binding to a novel type of p53-responsive element in their promoters. Our results demonstrate that Δ113p53/Δ133p53 is an evolutionally conserved pro-survival factor for DNA damage stress by preventing apoptosis and promoting DNA DSB repair to inhibit cell senescence. Our data also suggest that the induction of Δ133p53 expression in normal cells or tissues provides an important tolerance marker for cancer patients to radiotherapy.

Temperature and Oxidative Stress as Triggers for Virulence Gene Expression in Pathogenic Leptospira spp.

PubMed Central

Fraser, Tricia; Brown, Paul D.

2017-01-01

Leptospirosis is a zooanthroponosis aetiologically caused by pathogenic bacteria belonging to the genus, Leptospira. Environmental signals such as increases in temperatures or oxidative stress can trigger response regulatory modes of virulence genes during infection. This study sought to determine the effect of temperature and oxidative stress on virulence associated genes in highly passaged Leptospira borgpeterseneii Jules and L. interrogans Portlandvere. Bacteria were grown in EMJH at 30°C, 37°C, or at 30°C before being transferred to 37°C. A total of 14 virulence-associated genes (fliY, invA, lenA, ligB, lipL32, lipL36, lipL41, lipL45, loa22, lsa21, mce, ompL1, sph2, and tlyC) were assessed using endpoint PCR. Transcriptional analyses of lenA, lipL32, lipL41, loa22, sph2 were assessed by quantitative real-time RT-PCR at the temperature conditions. To assess oxidative stress, bacteria were exposed to H2O2 for 30 and 60 min with or without the temperature stress. All genes except ligB (for Portlandvere) and ligB and mce (for Jules) were detectable in the strains. Quantitatively, temperature stress resulted in significant changes in gene expression within species or between species. Temperature changes were more influential in gene expression for Jules, particularly at 30°C and upshift conditions; at 37°C, expression levels were higher for Portlandvere. However, compared to Jules, where temperature was influential in two of five genes, temperature was an essential element in four of five genes in Portlandvere exposed to oxidative stress. At both low and high oxidative stress levels, the interplay between genetic predisposition (larger genome size) and temperature was biased towards Portlandvere particularly at 30°C and upshift conditions. While it is clear that expression of many virulence genes in highly passaged strains of Leptospira are attenuated or lost, genetic predisposition, changes in growth temperature and/or oxidative intensity and/or duration were factors which acted in isolation or together with other regulatory cues to contribute to the variable gene expression observed in this study. Overall, differential gene expression in serovar Portlandvere was more responsive to temperature and oxidative stress. PMID:28536558

Refining the timing of the MIS 5e signal, West Caicos, Bristish West Indies:implications for paleoclimatic interpretation of the stratigraphic record

NASA Astrophysics Data System (ADS)

Kerans, C.; Zahm, C.; Bachtel, S.; Hearty, P.; Cheng, H.

2017-12-01

The progressive refinement of the Last Interglacial (LIG) tropical carbonate record has focused attention on the dramatically abrupt and episodic nature of this critical approximate 12 ka time window. From initial carbonate platform flooding at 133 ka to rapid sea level fall and exposure at 118 ka, the majority of present-day Bahamian and Caribbean strata were produced in a remarkably similar pattern extending from Bermuda and the Bahamas through the Cayman Islands, Yucatan, and south to the Dominican Republic. The position of coral reefs and oolitic sands of the LIG to a first order fit the global insolation-driven climate warming signal. Less well accepted/resolved is the existence of two distinct SL peaks with an intervening sea level fall implying a non-orbitally forced climate shift during this broader highstand. West Caicos, a 10 x 5 km leeward island on the Caicos Platform is an excellent example of LIG carbonate stratigraphic complexity. We collected sub-meter-resolution whole-island airborn LIDAR and decimeter-resolution UAV-constructed DEM's of the western and southern coastal outcrops to serve as a base for decimeter-scale mapping of the MIS 11, 7?, 5e, and Holocene units of the island, with particular focus on the continuous 8.4 km west coast outcrop of the MIS 5e. Seventy-five AAR relative age assignments from ooid separates, pinned by 16 U/Th dates from corals coming from MIS stage 11, lower MIS 5e, and upper MIS 5e reefs helped establish the age model for the Pleistocene-Holocene stratigraphy. The lower MIS 5e reef system averages 128 ka with an onset age of 133 ka. Upper MIS 5e corals ranges from 123 ka to 116 ka, bracketing the intra-MIS 5e sea-level fall between to approximately 125 ka. The intra-MIS 5e fall is a distinct erosional unconformity across 5 km of continuous outcrop, truncating the upper 2.5 m of lower 5e reef. The complexity of MIS 5e record on West Caicos and in the Northern Atlantic and Caribbean platforms regionally provides important insights for those using the Pleistocene as a model for older stratigraphic successions and their linked paleoclimatic records.

North American Monsoon Response to Eemian Climate Forcings and its Effect on Rocky Mountain Forests

NASA Astrophysics Data System (ADS)

Insel, N.; Berkelhammer, M. B.

2017-12-01

The key to recognizing and predicting future changes in regional climate and ecosystems lies in understanding the causes and characteristics of paleovariations. The Last Interglacial (LIG: 130-116 ka) is the most recent period in Earth history when temperatures are believed to have exceeded those of today. In this study, we are focusing on the response of the North American monsoon (NAM) to shifts in orbital forcings during LIG. In particular, we are using regional climate model (RegCM) simulations under LIG (115ka, 125 ka and 135 ka) and modern forcings to evaluate changes in the strength, timing, duration, and amount of moisture transported from different sources during the NAM season. Understanding these variations is critical to forecast seasonal supply of water to the southwestern U.S. under current warming conditions. In addition, cellulose extracted stable isotopes from Rocky Mountain Eemian wood samples provides both a tool to diagnose the model simulations and to evaluate the response of western U.S. tree species to changes in temperature and moisture availability. Our preliminary results indicate enhanced summer precipitation, wind shifts and changes in NAM characteristics in response to increased Northern Hemisphere insolation. The following features were observed: (1) The NAM strengthens and extends slightly more northward during the Eemian due to a shift in upper-level divergence. (2) The onset and duration of the NAM seems to be similar between modern and Eemian simulations. (3) Consistent with modern observations, simulations suggest a western NAM region in Arizona that receives most of its monsoonal moisture from the Gulf of California, while the eastern NAM region in New Mexico obtains most of its summer rains from the Gulf of Mexico. In the Eemian, we see a spatial shift from more depleted to more enriched source waters throughout the monsoon season. These changes in the summer climate are confirmed by the tree ring isotope data, which show a clear increase in δ18O late in the growing season suggesting a change in water source or water stress. Ongoing simulations will be used to address the question of whether increased access to moisture sources offset the negative impact of earlier snowmelt on tree growth.

The Mu.Ta.Lig. Chemotheca: A community-populated molecular database for multi-target ligands identification and compound-repurposing

NASA Astrophysics Data System (ADS)

Ortuso, Francesco; Bagetta, Donatella; Maruca, Annalisa; Talarico, Carmine; Bolognesi, Maria L.; Haider, Norbert; Borges, Fernanda; Bryant, Sharon; Langer, Thierry; Senderowitz, Hanoch; Alcaro, Stefano

2018-04-01

Abstract For every lead compound developed in medicinal chemistry research, numerous other inactive or less active candidates are synthetized/isolated and tested. The majority of these compounds will not be selected for further development due to a sub-optimal pharmacological profile. However, some poorly active or even inactive compounds could live a second life if tested against other targets. Thus, new therapeutic opportunities could emerge and synergistic activities could be identified and exploited for existing compounds by sharing information between researchers who are working on different targets. The Mu.Ta.Lig (Multi-Target Ligand) Chemotheca database aims to offer such opportunities by facilitating information exchange among researchers worldwide. After a preliminary registration, users can (a) virtually upload structures and activity data for their compounds with corresponding, and eventually known activity data, and (b) search for other available compounds uploaded by the users community. Each piece of information about given compounds is owned by the user who initially uploaded it and multiple ownership is possible (occurs if different users uploaded the same compounds or information pertaining to the same compounds). A web-based graphical user interface has been developed to assist compound uploading, compounds searching and data retrieval. Physico-chemical and ADME properties as well as substructure-based PAINS evaluations are computed on the fly for each uploaded compound. Samples of compounds that match a set of search criteria and additional data on these compounds could be requested directly from their owners with no mediation by the Mu.Ta.Lig Chemotheca team. Guest access provides a simplified search interface to retrieve only basic information such as compound IDs and related 2D or 3D chemical structures. Moreover, some compounds can be hidden from Guest users according to an owner’s decision. In contrast, registered users have full access to all of the Chemotheca data including the permission to upload new compounds and/or update experimental/theoretical data (e.g., activities against new targets tested) related to already stored compounds. In order to facilitate scientific collaborations, all available data are connected to the corresponding owner’s email address (available for registered users only). The Chemotheca web site is accessible at http://chemotheca.unicz.it.

The Mu.Ta.Lig. Chemotheca: A Community-Populated Molecular Database for Multi-Target Ligands Identification and Compound-Repurposing.

PubMed

Ortuso, Francesco; Bagetta, Donatella; Maruca, Annalisa; Talarico, Carmine; Bolognesi, Maria L; Haider, Norbert; Borges, Fernanda; Bryant, Sharon; Langer, Thierry; Senderowitz, Hanoch; Alcaro, Stefano

2018-01-01

For every lead compound developed in medicinal chemistry research, numerous other inactive or less active candidates are synthetized/isolated and tested. The majority of these compounds will not be selected for further development due to a sub-optimal pharmacological profile. However, some poorly active or even inactive compounds could live a second life if tested against other targets. Thus, new therapeutic opportunities could emerge and synergistic activities could be identified and exploited for existing compounds by sharing information between researchers who are working on different targets. The Mu.Ta.Lig (Multi-Target Ligand) Chemotheca database aims to offer such opportunities by facilitating information exchange among researchers worldwide. After a preliminary registration, users can (a) virtually upload structures and activity data for their compounds with corresponding, and eventually known activity data, and (b) search for other available compounds uploaded by the users community. Each piece of information about given compounds is owned by the user who initially uploaded it and multiple ownership is possible (this occurs if different users uploaded the same compounds or information pertaining to the same compounds). A web-based graphical user interface has been developed to assist compound uploading, compounds searching and data retrieval. Physico-chemical and ADME properties as well as substructure-based PAINS evaluations are computed on the fly for each uploaded compound. Samples of compounds that match a set of search criteria and additional data on these compounds could be requested directly from their owners with no mediation by the Mu.Ta.Lig Chemotheca team. Guest access provides a simplified search interface to retrieve only basic information such as compound IDs and related 2D or 3D chemical structures. Moreover, some compounds can be hidden to Guest users according to an owner's decision. In contrast, registered users have full access to all of the Chemotheca data including the permission to upload new compounds and/or update experimental/theoretical data (e.g., activities against new targets tested) related to already stored compounds. In order to facilitate scientific collaborations, all available data are connected to the corresponding owner's email address (available for registered users only). The Chemotheca web site is accessible at http://chemotheca.unicz.it.

Logistics and Maintenance Concepts for a Future Naval Force

DTIC Science & Technology

2001-12-01

Co - opetition . Currency-Doubleday. Retrieved December 10, 2001 from...Navigation CND Can Not Duplicate CO Commanding Officer COMNAVAIRLANT Commander Naval Forces Atlantic COSAL Consolidated Ship Allowance List CPO...ra ul ic s C or ro si on , O pe ra tio na l f lig ht co nt ro ls de gr ad at io n W id es pr ea d W ir e D am ag e X X X X X X X X

A Self-Assembling Protein Hydrogel Technology for Enzyme Incorporation onto Electrodes in Biofuel Cells

DTIC Science & Technology

2015-10-26

amount of the product J and the unreacted N/C in the same lane. Figure 2. Crystal structure of Tip1-Tip1lig ( PDB code: 3IDW). (A...stability (able to retain its trimeric quaternary structure in solutions after boiling in SDS buffer). We reasoned that its very strong...109, 10 is a flexible polyanionic linker and was incorporated as the midblock for water retention. Mixing of the two protein block copolymers

Imaging monitoring techniques applications in the transient gratings detection

NASA Astrophysics Data System (ADS)

Zhao, Qing-ming

2009-07-01

Experimental studies of Degenerate four-wave mixing (DFWM) in iodine vapor at atmospheric pressure and 0℃ and 25℃ are reported. The Laser-induced grating (LIG) studies are carried out by generating the thermal grating using a pulsed, narrow bandwidth, dye laser .A new image processing system for detecting forward DFWM spectroscopy on iodine vapor is reported. This system is composed of CCD camera, imaging processing card and the related software. With the help of the detecting system, phase matching can be easily achieved in the optical arrangement by crossing the two pumps and the probe as diagonals linking opposite corners of a rectangular box ,and providing a way to position the PhotoMultiplier Tube (PMT) . Also it is practical to know the effect of the pointing stability on the optical path by monitoring facula changing with the laser beam pointing and disturbs of the environment. Finally the effects of Photostability of dye laser on the ration of signal to noise in DFWM using forward geometries have been investigated in iodine vapor. This system makes it feasible that the potential application of FG-DFWM is used as a diagnostic tool in combustion research and environment monitoring.

Production of a Novel OX40 Ligand for Clinical Use

DTIC Science & Technology

2015-10-01

several documented mechanisms. Our group has developed a technique to enhance immune function in tumor-bearing hosts by targeting a protein on the surface...immune function in tumor-bearing hosts through the use of OX40 agonists, which can lead to regression of tumors of various histologies, including...prostate cancer. In particular, we have produced a human OX40 agonist, termed OX40L:ILZ:Ig (OX40L:Ig) that has potent biologic function in vitro and is

Widespread Dependence of Backup NHEJ on Growth State: Ramifications for the Use of DNA-PK Inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, Satyendra K.; Wu Wenqi; Zhang Lihua

2011-02-01

Purpose: The backup pathway of nonhomologous end joining (B-NHEJ) enables cells to process DNA double-strand breaks (DSBs) when the DNA-PK-dependent pathway of NHEJ (D-NHEJ) is compromised. Our previous results show marked reduction in the activity of B-NHEJ when LIG4{sup -/-} mouse embryo fibroblasts (MEFs) cease to grow and enter a plateau phase. The dependence of B-NHEJ on growth state is substantially stronger than that of D-NHEJ and points to regulatory mechanisms or processing determinants that require elucidation. Because the different D-NHEJ mutants show phenotypes distinct in their details, it is necessary to characterize the dependence of their DSB repair capacitymore » on growth state and to explore species-specific responses. Methods and Materials: DSB repair was measured in cells of different genetic background from various species using pulsed-field gel electrophoresis, or the formation of {gamma}-H2AX foci, at different stages of growth. Results: Using pulsed-field gel electrophoresis, we report a marked reduction of B-NHEJ during the plateau phase of growth in KU and XRCC4, mouse or Chinese hamster, mutants. Notably, this reduction is only marginal in DNA-PKcs-deficient cells. However, reduced B-NHEJ is also observed in repair proficient, plateau-phase cells after treatment with DNA-PK inhibitors. The reduction of B-NHEJ activity in the plateau phase of growth does not derive from the reduced expression of participating proteins, is detectable by {gamma}-H2AX foci analysis, and leads to enhanced cell killing. Conclusions: These results further document the marked dependence on growth state of an essential DSB repair pathway and show the general nature of the effect. Molecular characterization of the mechanism underlying this response will help to optimize the administration of DNA repair inhibitors as adjuvants in radiation therapy.« less

Role for Artemis nuclease in the repair of radiation-induced DNA double strand breaks by alternative end joining.

PubMed

Moscariello, Mario; Wieloch, Radi; Kurosawa, Aya; Li, Fanghua; Adachi, Noritaka; Mladenov, Emil; Iliakis, George

2015-07-01

Exposure of cells to ionizing radiation or radiomimetic drugs generates DNA double-strand breaks that are processed either by homologous recombination repair (HRR), or by canonical, DNA-PKcs-dependent non-homologous end-joining (C-NHEJ). Chemical or genetic inactivation of factors involved in C-NHEJ or HRR, but also their local failure in repair proficient cells, promotes an alternative, error-prone end-joining pathway that serves as backup (A-EJ). There is evidence for the involvement of Artemis endonuclease, a protein deficient in a human radiosensitivity syndrome associated with severe immunodeficiency (RS-SCID), in the processing of subsets of DSBs by HRR or C-NHEJ. It is thought that within HRR or C-NHEJ Artemis processes DNA termini at complex DSBs. Whether Artemis has a role in A-EJ remains unknown. Here, we analyze using pulsed-field gel electrophoresis (PFGE) and specialized reporter assays, DSB repair in wild-type pre-B NALM-6 lymphocytes, as well as in their Artemis(-/-), DNA ligase 4(-/-) (LIG4(-/-)), and LIG4(-/-)/Artemis(-/-) double mutant counterparts, under conditions allowing evaluation of A-EJ. Our results substantiate the suggested roles of Artemis in C-NHEJ and HRR, but also demonstrate a role for the protein in A-EJ that is confirmed in Artemis deficient normal human fibroblasts. We conclude that Artemis is a nuclease participating in DSB repair by all major repair pathways. Copyright © 2015 Elsevier B.V. All rights reserved.

Speech profile of patients undergoing primary palatoplasty.

PubMed

Menegueti, Katia Ignacio; Mangilli, Laura Davison; Alonso, Nivaldo; Andrade, Claudia Regina Furquim de

2017-10-26

To characterize the profile and speech characteristics of patients undergoing primary palatoplasty in a Brazilian university hospital, considering the time of intervention (early, before two years of age; late, after two years of age). Participants were 97 patients of both genders with cleft palate and/or cleft and lip palate, assigned to the Speech-language Pathology Department, who had been submitted to primary palatoplasty and presented no prior history of speech-language therapy. Patients were divided into two groups: early intervention group (EIG) - 43 patients undergoing primary palatoplasty before 2 years of age and late intervention group (LIG) - 54 patients undergoing primary palatoplasty after 2 years of age. All patients underwent speech-language pathology assessment. The following parameters were assessed: resonance classification, presence of nasal turbulence, presence of weak intraoral air pressure, presence of audible nasal air emission, speech understandability, and compensatory articulation disorder (CAD). At statistical significance level of 5% (p≤0.05), no significant difference was observed between the groups in the following parameters: resonance classification (p=0.067); level of hypernasality (p=0.113), presence of nasal turbulence (p=0.179); presence of weak intraoral air pressure (p=0.152); presence of nasal air emission (p=0.369), and speech understandability (p=0.113). The groups differed with respect to presence of compensatory articulation disorders (p=0.020), with the LIG presenting higher occurrence of altered phonemes. It was possible to assess the general profile and speech characteristics of the study participants. Patients submitted to early primary palatoplasty present better speech profile.

Constraints on the thermosteric component of Last Interglacial sea level

NASA Astrophysics Data System (ADS)

Shackleton, S. A.; Severinghaus, J. P.; Petrenko, V. V.; Dyonisius, M.; Hmiel, B.

2016-12-01

With global temperatures 1 to 2°C above preindustrial, but sea level exceeding current levels by upwards of 8 meters, the Last Interglacial (LIG) period at 125 ka may provide valuable insight into Earth system constraints under future global warming. The relative contributions of thermal expansion and ice sheet loss to sea level rise over this period are of particular interest in seeking to improve sea level projections in the upcoming decades and beyond. Here we quantify this thermosteric component from a reconstruction of global ocean temperature over the LIG from atmospheric noble gases trapped in glacial ice. With no major sources or sinks outside of the ocean-atmosphere system, the relative changes in the atmospheric content of krypton, xenon, and nitrogen reflect changes in ocean gas storage. This storage is primarily governed by solubility and ocean temperature, making dKr/N2, dXe/N2­, and dXe/Kr unique tracers of globally integrated oceanic heat content. However, processes within the firn can fractionate these gases, and firn effects on these tracers must be removed to derive an ocean temperature. We present high precision measurements of these gas ratios along with isotopes of argon, krypton, and xenon in firn air withdrawn from the snowpack at Summit, Greenland. We use these isotopes to identify sources of fractionation within the firn and quantify their effects on the noble gas tracers, enabling a reconstruction of Last Interglacial ocean temperature.

Simulation of the Greenland Ice Sheet over two glacial-interglacial cycles: investigating a sub-ice-shelf melt parameterization and relative sea level forcing in an ice-sheet-ice-shelf model

NASA Astrophysics Data System (ADS)

Bradley, Sarah L.; Reerink, Thomas J.; van de Wal, Roderik S. W.; Helsen, Michiel M.

2018-05-01

Observational evidence, including offshore moraines and sediment cores, confirm that at the Last Glacial Maximum (LGM) the Greenland ice sheet (GrIS) expanded to a significantly larger spatial extent than seen at present, grounding into Baffin Bay and out onto the continental shelf break. Given this larger spatial extent and its close proximity to the neighbouring Laurentide Ice Sheet (LIS) and Innuitian Ice Sheet (IIS), it is likely these ice sheets will have had a strong non-local influence on the spatial and temporal behaviour of the GrIS. Most previous paleo ice-sheet modelling simulations recreated an ice sheet that either did not extend out onto the continental shelf or utilized a simplified marine ice parameterization which did not fully include the effect of ice shelves or neglected the sensitivity of the GrIS to this non-local bedrock signal from the surrounding ice sheets. In this paper, we investigated the evolution of the GrIS over the two most recent glacial-interglacial cycles (240 ka BP to the present day) using the ice-sheet-ice-shelf model IMAU-ICE. We investigated the solid earth influence of the LIS and IIS via an offline relative sea level (RSL) forcing generated by a glacial isostatic adjustment (GIA) model. The RSL forcing governed the spatial and temporal pattern of sub-ice-shelf melting via changes in the water depth below the ice shelves. In the ensemble of simulations, at the glacial maximums, the GrIS coalesced with the IIS to the north and expanded to the continental shelf break to the southwest but remained too restricted to the northeast. In terms of the global mean sea level contribution, at the Last Interglacial (LIG) and LGM the ice sheet added 1.46 and -2.59 m, respectively. This LGM contribution by the GrIS is considerably higher (˜ 1.26 m) than most previous studies whereas the contribution to the LIG highstand is lower (˜ 0.7 m). The spatial and temporal behaviour of the northern margin was highly variable in all simulations, controlled by the sub-ice-shelf melting which was dictated by the RSL forcing and the glacial history of the IIS and LIS. In contrast, the southwestern part of the ice sheet was insensitive to these forcings, with a uniform response in all simulations controlled by the surface air temperature, derived from ice cores.

Exposure to Nickel, Chromium, or Cadmium Causes Distinct Changes in the Gene Expression Patterns of a Rat Liver Derived Cell Line

DTIC Science & Technology

2011-11-16

protein A (Rpa2), the minichromosome maintenance complex component genes which encode helicases, DNA ligase (Lig1), DNA polymerase e ( Pole and Pole2...and DNA polymerase d ( Pold1 and Pold2 ) are all up-regulated as a result of exposure to chromium (Figure 6), suggesting that there is an increase in...Exposure to Nickel, Chromium, or Cadmium Causes Distinct Changes in the Gene Expression Patterns of a Rat Liver Derived Cell Line Matthew G

The perturbation of tryptophan fluorescence by phenylalanine to alanine mutations identifies the hydrophobic core in a subset of bacterial Ig-like domains.

PubMed

Raman, Rajeev; Ptak, Christopher P; Hsieh, Ching-Lin; Oswald, Robert E; Chang, Yung-Fu; Sharma, Yogendra

2013-07-09

Many host-parasite interactions are mediated via surface-exposed proteins containing bacterial immunoglobulin-like (Big) domains. Here, we utilize the spectral properties of a conserved Trp to provide evidence that, along with a Phe, these residues are positioned within the hydrophobic core of a subset of Big_2 domains. The mutation of the Phe to Ala decreases Big_2 domain stability and impairs the ability of LigBCen2 to bind to the host protein, fibronectin.

Cell Cycle Dependent Regulation of Human Progesterone Receptor in Breast Cancer

DTIC Science & Technology

2004-10-01

wt PR or S400A PR (0.01-1.0 [tg each), CDK2 (ljig), and PRE-2x-TATA-luc reporter plasmid (lig) along with Renilla plasmid (10ng) as a control for...8 hours prior to treatment. Cells were collected following treatment with 10 nM R5020 or ETOH vehicle control for 18 hrs. Luciferase and renilla ...reporter, a renilla reporter construct as a transfection control, either wt PR-B or S400A mutant PR-B, and control parental vector or a vector encoding an

Liquid-Hydrogen-Cooled 450-hp Electric Motor Test Stand Being Developed

NASA Technical Reports Server (NTRS)

Kascak, Albert F.; Trudell, Jeffrey J.; Brown, Gerald V.

2005-01-01

With growing concerns about global warming, there is a need to develop pollution-free aircraft. One approach is to use hydrogen-fueled airc raft that use fuel cells or turbogenerators to produce electric power to drive the electric motors that turn the aircraft#s propulsive fan s. Hydrogen fuel would be carried as a liquid, stored at its boiling point of 20.5 K (-422.5 ?F). Conventional electric motors, however, are too heavy to use on an aircraft. We need to develop high-power, lig htweight electric motors (high-powerdensity motors).

Wastewater Characterization Survey, Plattsburgh AFB, New York.

DTIC Science & Technology

1987-05-01

day 1/6 months 24-hour composite Chromium 1.5 lbs/day 1/6 months 24-hour composite Cyanide (free) 1.5 lbs/day 1/6 months 24-hour composite Arsenic 1.5...pollutant. Average concentrations of iron, chromium , and zinc were 1.88 mg/1, 50 Lig/i, and 196.7 4g/l, respectively. The iron concentration exceeded the...iron, chromium , silver and zinc were 1.2 mg/l, 76 Wg/l, 44 ug/l, and 180 g/l, respectively. The iron concentration exceeded the EPA criterion for fresh

Measurement of Particle Size Distribution in a Solid Propellant Rocket Motor Using Light Scattering

DTIC Science & Technology

1987-06-01

RE>NTOF PARTICLE SIZE DISTRIBUTION IN A SOLID PROPELLA NT iRO7CET M -OTOR USING7V LIG-THT SCATTERI0- PERO’J: ABTHOS) 3j -*"i 0, REPORT 30 ,’ME COVERED...ENGINEERING SCIENCE from the NAVAL POSTGRADUATE SCHOOL " June 1987 Author: Ted E.Prqi Approved by: 61’ D. W. Netzer, Thesdvisor M . F. Platzer, Chairman...Motor Profile, 22 May .................... .......... 87 4.38 Motor Profile, 26 May ................................ 88 N) 4. 8 M t r P o i e 2 a

Hazardous Waste Technical Assistance Survey, Fairchild AFB, Washington

DTIC Science & Technology

1988-09-01

disposal is primarI"f the-: !--3,,Psp iih; o-1’ shoe -S gc-nearLig .na waste. Waste generators keep ;ogs on the ar-oL(0!, and.c types of ;D~:sc ino ili-jced...to the sanitary sewer. All paint waste skimmed off the top of the water is placed into a 55-gallon drum along with any sludge removed from the bottom...responsible for inspecting aircraft and aircraft parts for structural flaws using magnetic particle inspection and dye penetrant inspection. The magnetic

The rare isotope beams production at the Texas A and M university Cyclotron Institute

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tabacaru, G.; May, D. P.; Chubarian, G.

2013-04-19

The Cyclotron Institute at Texas A and M initiated an upgrade project for the production of radioactive-ion beams that incorporates a light-ion guide (LIG) and a heavy-ion guide coupled (HIG) with an Electron Cyclotron Resonance Ion Source (ECRIS) constructed for charge-boosting (CB-ECRIS). This scheme is intended to produce radioactive beams suitable for injection into the K500 superconducting cyclotron. The current status of the project and details on the ion sources and devices used in the project is presented.

Super-sensitive two-wavelength fringe projection profilometry with 2-sensitivities temporal unwrapping

NASA Astrophysics Data System (ADS)

Servin, Manuel; Padilla, Moises; Garnica, Guillermo

2018-07-01

Since the early 1970s, optical two-wavelength phase-metrology (TWPM) has been used in a wide variety of experimental set ups. In TWPM one may compute the phase-sum and the phase-difference of two close phase measurements. Early TWPM optically computed the phase difference and phase sum by double exposure holography. However soon after, TWPM became almost synonymous to calculating the phase-difference only. The more sensitive phase-sum was largely forgotten. The standard application for phase-difference TWPM is to extend the phase measurement depth without phase-unwrapping for discontinuous phase-objects. This phase-difference, while non-wrapped, decreases however the signal-to-noise ratio (SNR) of the estimated phase. On the other hand, the phase-sum increases the phase sensitivity, and the SNR of the estimated phase. In spite of these two great advantages, the use of the phase-sum in TWPM has been almost ignored. In this paper we review and set the stage for digital TWPM for super-sensitive phase-sum estimation. This is coupled with two-sensitivity phase-unwrapping to obtain extended-range super-sensitive fringe-projection profilometry estimations. Here we mathematically prove, and experimentally show that using the phase-sum one obtains a huge increase in SNR with respect to using the phase-difference alone. The pioneer works on double exposure TWPM holography that uses the phase-difference and phase-sum are also properly acknowledged. Finally, two experimental results from fringe-projection profilometry that clearly show the huge SNR gain of the phase-sum, with respect to the phase-difference is now mathematically well established.

The PMIP4 contribution to CMIP6 - Part 2: Two interglacials, scientific objective and experimental design for Holocene and Last Interglacial simulations

NASA Astrophysics Data System (ADS)

Otto-Bliesner, Bette L.; Braconnot, Pascale; Harrison, Sandy P.; Lunt, Daniel J.; Abe-Ouchi, Ayako; Albani, Samuel; Bartlein, Patrick J.; Capron, Emilie; Carlson, Anders E.; Dutton, Andrea; Fischer, Hubertus; Goelzer, Heiko; Govin, Aline; Haywood, Alan; Joos, Fortunat; LeGrande, Allegra N.; Lipscomb, William H.; Lohmann, Gerrit; Mahowald, Natalie; Nehrbass-Ahles, Christoph; Pausata, Francesco S. R.; Peterschmitt, Jean-Yves; Phipps, Steven J.; Renssen, Hans; Zhang, Qiong

2017-11-01

Two interglacial epochs are included in the suite of Paleoclimate Modeling Intercomparison Project (PMIP4) simulations in the Coupled Model Intercomparison Project (CMIP6). The experimental protocols for simulations of the mid-Holocene (midHolocene, 6000 years before present) and the Last Interglacial (lig127k, 127 000 years before present) are described here. These equilibrium simulations are designed to examine the impact of changes in orbital forcing at times when atmospheric greenhouse gas levels were similar to those of the preindustrial period and the continental configurations were almost identical to modern ones. These simulations test our understanding of the interplay between radiative forcing and atmospheric circulation, and the connections among large-scale and regional climate changes giving rise to phenomena such as land-sea contrast and high-latitude amplification in temperature changes, and responses of the monsoons, as compared to today. They also provide an opportunity, through carefully designed additional sensitivity experiments, to quantify the strength of atmosphere, ocean, cryosphere, and land-surface feedbacks. Sensitivity experiments are proposed to investigate the role of freshwater forcing in triggering abrupt climate changes within interglacial epochs. These feedback experiments naturally lead to a focus on climate evolution during interglacial periods, which will be examined through transient experiments. Analyses of the sensitivity simulations will also focus on interactions between extratropical and tropical circulation, and the relationship between changes in mean climate state and climate variability on annual to multi-decadal timescales. The comparative abundance of paleoenvironmental data and of quantitative climate reconstructions for the Holocene and Last Interglacial make these two epochs ideal candidates for systematic evaluation of model performance, and such comparisons will shed new light on the importance of external feedbacks (e.g., vegetation, dust) and the ability of state-of-the-art models to simulate climate changes realistically.

Phase-space evolution of x-ray coherence in phase-sensitive imaging.

PubMed

Wu, Xizeng; Liu, Hong

2008-08-01

X-ray coherence evolution in the imaging process plays a key role for x-ray phase-sensitive imaging. In this work we present a phase-space formulation for the phase-sensitive imaging. The theory is reformulated in terms of the cross-spectral density and associated Wigner distribution. The phase-space formulation enables an explicit and quantitative account of partial coherence effects on phase-sensitive imaging. The presented formulas for x-ray spectral density at the detector can be used for performing accurate phase retrieval and optimizing the phase-contrast visibility. The concept of phase-space shearing length derived from this phase-space formulation clarifies the spatial coherence requirement for phase-sensitive imaging with incoherent sources. The theory has been applied to x-ray Talbot interferometric imaging as well. The peak coherence condition derived reveals new insights into three-grating-based Talbot-interferometric imaging and gratings-based x-ray dark-field imaging.

Genetic variation in the base excision repair pathway and bladder cancer risk.

PubMed

Figueroa, Jonine D; Malats, Núria; Real, Francisco X; Silverman, Debra; Kogevinas, Manolis; Chanock, Stephen; Welch, Robert; Dosemeci, Mustafa; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Castaño-Vinyals, Gemma; Rothman, Nathaniel; García-Closas, Montserrat

2007-04-01

Genetic polymorphisms in DNA repair genes may impact individual variation in DNA repair capacity and alter cancer risk. In order to examine the association of common genetic variation in the base-excision repair (BER) pathway with bladder cancer risk, we analyzed 43 single nucleotide polymorphisms (SNPs) in 12 BER genes (OGG1, MUTYH, APEX1, PARP1, PARP3, PARP4, XRCC1, POLB, POLD1, PCNA, LIG1, and LIG3). Using genotype data from 1,150 cases of urinary bladder transitional cell carcinomas and 1,149 controls from the Spanish Bladder Cancer Study we estimated odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for age, gender, region and smoking status. SNPs in three genes showed significant associations with bladder cancer risk: the 8-oxoG DNA glycosylase gene (OGG1), the Poly (ADP-ribose) polymerase family member 1 (PARP1) and the major gap filling polymerase-beta (POLB). Subjects who were heterozygous or homozygous variant for an OGG1 SNP in the promoter region (rs125701) had significantly decreased bladder cancer risk compared to common homozygous: OR (95%CI) 0.78 (0.63-0.96). Heterozygous or homozygous individuals for the functional SNP PARP1 rs1136410 (V762A) or for the intronic SNP POLB rs3136717 were at increased risk compared to those homozygous for the common alleles: 1.24 (1.02-1.51) and 1.30 (1.04-1.62), respectively. In summary, data from this large case-control study suggested bladder cancer risk associations with selected BER SNPs, which need to be confirmed in other study populations.

Latitudinal environmental niches and riverine barriers shaped the phylogeography of the Central Chilean endemic Dioscorea humilis (Dioscoreaceae).

PubMed

Viruel, Juan; Catalán, Pilar; Segarra-Moragues, José Gabriel

2014-01-01

The effects of Pleistocene glaciations and geographical barriers on the phylogeographic patterns of lowland plant species in Mediterranean-climate areas of Central Chile are poorly understood. We used Dioscorea humilis (Dioscoreaceae), a dioecious geophyte extending 530 km from the Valparaíso to the Bío-Bío Regions, as a case study to disentangle the spatio-temporal evolution of populations in conjunction with latitudinal environmental changes since the Last Inter-Glacial (LIG) to the present. We used nuclear microsatellite loci, chloroplast (cpDNA) sequences and environmental niche modelling (ENM) to construct current and past scenarios from bioclimatic and geographical variables and to infer the evolutionary history of the taxa. We found strong genetic differentiation at nuclear microsatellite loci between the two subspecies of D. humilis, probably predating the LIG. Bayesian analyses of population structure revealed strong genetic differentiation of the widespread D. humilis subsp. humilis into northern and southern population groups, separated by the Maipo river. ENM revealed that the ecological niche differentiation of both groups have been maintained up to present times although their respective geographical distributions apparently fluctuated in concert with the climatic oscillations of the Last Glacial Maximum (LGM) and the Holocene. Genetic data revealed signatures of eastern and western postglacial expansion of the northern populations from the central Chilean depression, whereas the southern ones experienced a rapid southward expansion after the LGM. This study describes the complex evolutionary histories of lowland Mediterranean Chilean plants mediated by the summed effects of spatial isolation caused by riverine geographical barriers and the climatic changes of the Quaternary.

Latitudinal Environmental Niches and Riverine Barriers Shaped the Phylogeography of the Central Chilean Endemic Dioscorea humilis (Dioscoreaceae)

PubMed Central

Viruel, Juan; Catalán, Pilar; Segarra-Moragues, José Gabriel

2014-01-01

The effects of Pleistocene glaciations and geographical barriers on the phylogeographic patterns of lowland plant species in Mediterranean-climate areas of Central Chile are poorly understood. We used Dioscorea humilis (Dioscoreaceae), a dioecious geophyte extending 530 km from the Valparaíso to the Bío-Bío Regions, as a case study to disentangle the spatio-temporal evolution of populations in conjunction with latitudinal environmental changes since the Last Inter-Glacial (LIG) to the present. We used nuclear microsatellite loci, chloroplast (cpDNA) sequences and environmental niche modelling (ENM) to construct current and past scenarios from bioclimatic and geographical variables and to infer the evolutionary history of the taxa. We found strong genetic differentiation at nuclear microsatellite loci between the two subspecies of D. humilis, probably predating the LIG. Bayesian analyses of population structure revealed strong genetic differentiation of the widespread D. humilis subsp. humilis into northern and southern population groups, separated by the Maipo river. ENM revealed that the ecological niche differentiation of both groups have been maintained up to present times although their respective geographical distributions apparently fluctuated in concert with the climatic oscillations of the Last Glacial Maximum (LGM) and the Holocene. Genetic data revealed signatures of eastern and western postglacial expansion of the northern populations from the central Chilean depression, whereas the southern ones experienced a rapid southward expansion after the LGM. This study describes the complex evolutionary histories of lowland Mediterranean Chilean plants mediated by the summed effects of spatial isolation caused by riverine geographical barriers and the climatic changes of the Quaternary. PMID:25295517

Genome-wide identification, characterization and classification of ionotropic glutamate receptor genes (iGluRs) in the malaria vector Anopheles sinensis (Diptera: Culicidae).

PubMed

Wang, Ting-Ting; Si, Feng-Ling; He, Zheng-Bo; Chen, Bin

2018-01-15

Ionotropic glutamate receptors (iGluRs) are conserved ligand-gated ion channel receptors, and ionotropic receptors (IRs) were revealed as a new family of iGluRs. Their subdivision was unsettled, and their characteristics are little known. Anopheles sinensis is a major malaria vector in eastern Asia, and its genome was recently well sequenced and annotated. We identified iGluR genes in the An. sinensis genome, analyzed their characteristics including gene structure, genome distribution, domains and specific sites by bioinformatic methods, and deduced phylogenetic relationships of all iGluRs in An. sinensis, Anopheles gambiae and Drosophila melanogaster. Based on the characteristics and phylogenetics, we generated the classification of iGluRs, and comparatively analyzed the intron number and selective pressure of three iGluRs subdivisions, iGluR group, Antenna IR and Divergent IR subfamily. A total of 56 iGluR genes were identified and named in the whole-genome of An. sinensis. These genes were located on 18 scaffolds, and 31 of them (29 being IRs) are distributed into 10 clusters that are suggested to form mainly from recent gene duplication. These iGluRs can be divided into four groups: NMDA, non-NMDA, Antenna IR and Divergent IR based on feature comparison and phylogenetic analysis. IR8a and IR25a were suggested to be monophyletic, named as Putative in the study, and moved from the Antenna subfamily in the IR family to the non-NMDA group as a sister of traditional non-NMDA. The generated iGluRs of genes (including NMDA and regenerated non-NMDA) are relatively conserved, and have a more complicated gene structure, smaller ω values and some specific functional sites. The iGluR genes in An. sinensis, An. gambiae and D. melanogaster have amino-terminal domain (ATD), ligand binding domain (LBD) and Lig_Chan domains, except for IR8a that only has the LBD and Lig_Chan domains. However, the new concept IR family of genes (including regenerated Antenna IR, and Divergent IR), especially for Divergent IR are more variable, have a simpler gene structure (intron loss phenomenon) and larger ω values, and lack specific functional sites. These IR genes have no other domains except for Antenna IRs that only have the Lig_Chan domain. This study provides a comprehensive information framework for iGluR genes in An. sinensis, and generated the classification of iGluRs by feature and bioinformatics analyses. The work lays the foundation for further functional study of these genes.

Comparing phase-sensitive and phase-insensitive echolocation target images using a monaural audible sonar.

PubMed

Kuc, Roman

2018-04-01

This paper describes phase-sensitive and phase-insensitive processing of monaural echolocation waveforms to generate target maps. Composite waveforms containing both the emission and echoes are processed to estimate the target impulse response using an audible sonar. Phase-sensitive processing yields the composite signal envelope, while phase-insensitive processing that starts with the composite waveform power spectrum yields the envelope of the autocorrelation function. Analysis and experimental verification show that multiple echoes form an autocorrelation function that produces near-range phantom-reflector artifacts. These artifacts interfere with true target echoes when the first true echo occurs at a time that is less than the total duration of the target echoes. Initial comparison of phase-sensitive and phase-insensitive maps indicates that both display important target features, indicating that phase is not vital. A closer comparison illustrates the improved resolution of phase-sensitive processing, the near-range phantom-reflectors produced by phase-insensitive processing, and echo interference and multiple reflection artifacts that were independent of the processing.

Water storage in marine sediment and implications for inferences of past global ice volume

NASA Astrophysics Data System (ADS)

Ferrier, K.; Li, Q.; Pico, T.; Austermann, J.

2017-12-01

Changes in past sea level are of wide interest because they provide information on the sensitivity of ice sheets to climate change, and thus inform predictions of future sea-level change. Sea level changes are influenced by many processes, including the storage of water in sedimentary pore space. Here we use a recent extension of gravitationally self-consistent sea-level models to explore the effects of marine sedimentary water storage on the global seawater balance and inferences of past global ice volume. Our analysis suggests that sedimentary water storage can be a significant component of the global seawater budget over the 105-year timescales associated with glacial-interglacial cycles, and an even larger component over longer timescales. Estimates of global sediment fluxes to the oceans suggest that neglecting marine sedimentary water storage may produce meter-scale errors in estimates of peak global mean sea level equivalent (GMSL) during the Last Interglacial (LIG). These calculations show that marine sedimentary water storage can be a significant contributor to the overall effects of sediment redistribution on sea-level change, and that neglecting sedimentary water storage can lead to substantial errors in inferences of global ice volume at past interglacials. This highlights the importance of accounting for the influences of sediment fluxes and sedimentary water storage on sea-level change over glacial-interglacial timescales.

Design principles for enhancing phase sensitivity and suppressing phase fluctuations simultaneously in biochemical oscillatory systems.

PubMed

Fei, Chenyi; Cao, Yuansheng; Ouyang, Qi; Tu, Yuhai

2018-04-12

Biological systems need to function accurately in the presence of strong noise and at the same time respond sensitively to subtle external cues. Here we study design principles in biochemical oscillatory circuits to achieve these two seemingly incompatible goals. We show that energy dissipation can enhance phase sensitivity linearly by driving the phase-amplitude coupling and increase timing accuracy by suppressing phase diffusion. Two general design principles in the key underlying reaction loop formed by two antiparallel pathways are found to optimize oscillation performance with a given energy budget: balancing the forward-to-backward flux ratio between the two pathways to reduce phase diffusion and maximizing the net flux of the phase-advancing pathway relative to that of the phase-retreating pathway to enhance phase sensitivity. Experimental evidences consistent with these design principles are found in the circadian clock of cyanobacteria. Future experiments to test the predicted dependence of phase sensitivity on energy dissipation are proposed.

Binaural interaction in low-frequency neurons in inferior colliculus of the cat. II. Effects of changing rate and direction of interaural phase.

PubMed

Yin, T C; Kuwada, S

1983-10-01

We used the binaural beat stimulus to study the interaural phase sensitivity of inferior colliculus (IC) neurons in the cat. The binaural beat, produced by delivering tones of slightly different frequencies to the two ears, generates continuous and graded changes in interaural phase. Over 90% of the cells that exhibit a sensitivity to changes in the interaural delay also show a sensitivity to interaural phase disparities with the binaural beat. Cells respond with a burst of impulses with each complete cycle of the beat frequency. The period histogram obtained by binning the poststimulus time histogram on the beat frequency gives a measure of the interaural phase sensitivity of the cell. In general, there is good correspondence in the shapes of the period histograms generated from binaural beats and the interaural phase curves derived from interaural delays and in the mean interaural phase angle calculated from them. The magnitude of the beat frequency determines the rate of change of interaural phase and the sign determines the direction of phase change. While most cells respond in a phase-locked manner up to beat frequencies of 10 Hz, there are some cells tht will phase lock up to 80 Hz. Beat frequency and mean interaural phase angle are linearly related for most cells. Most cells respond equally in the two directions of phase change and with different rates of change, at least up to 10 Hz. However, some IC cells exhibit marked sensitivity to the speed of phase change, either responding more vigorously at low beat frequencies or at high beat frequencies. In addition, other cells demonstrate a clear directional sensitivity. The cells that show sensitivity to the direction and speed of phase changes would be expected to demonstrate a sensitivity to moving sound sources in the free field. Changes in the mean interaural phase of the binaural beat period histograms are used to determine the effects of changes in average and interaural intensity on the phase sensitivity of the cells. The effects of both forms of intensity variation are continuously distributed. The binaural beat offers a number of advantages for studying the interaural phase sensitivity of binaural cells. The dynamic characteristics of the interaural phase can be varied so that the speed and direction of phase change are under direct control. The data can be obtained in a much more efficient manner, as the binaural beat is about 10 times faster in terms of data collection than the interaural delay.

The impact of Quaternary climate oscillations on divergence times and historical population sizes in Thylamys opossums from the Andes.

PubMed

Giarla, Thomas C; Jansa, Sharon A

2015-05-01

Climate oscillations during the Quaternary altered the distributions of terrestrial animals at a global scale. In mountainous regions, temperature fluctuations may have led to shifts in range size and population size as species tracked their shifting habitats upslope or downslope. This creates the potential for both allopatric speciation and population size fluctuations, as species are either constrained to smaller patches of habitat at higher elevations or able to expand into broader areas at higher latitudes. We considered the impact of climate oscillations on three pairs of marsupial species from the Andes (Thylamys opossums) by inferring divergence times and demographic changes. We compare four different divergence dating approaches, using anywhere from one to 26 loci. Each pair comprises a northern (tropical) lineage and a southern (subtropical to temperate) lineage. We predicted that divergences would have occurred during the last interglacial (LIG) period approximately 125 000 years ago and that population sizes for northern and southern lineages would either contract or expand, respectively. Our results suggest that all three north-south pairs diverged in the late Pleistocene during or slightly after the LIG. The three northern lineages showed no signs of population expansion, whereas two southern lineages exhibited dramatic, recent expansions. We attribute the difference in responses between tropical and subtropical lineages to the availability of 'montane-like' habitats at lower elevations in regions at higher latitudes. We conclude that climate oscillations of the late Quaternary had a powerful impact on the evolutionary history of some of these species, both promoting speciation and leading to significant population size shifts. © 2015 John Wiley & Sons Ltd.

Reduced expression of DNA repair genes and chemosensitivity in 1p19q codeleted lower-grade gliomas.

PubMed

Tang, Lei; Deng, Lu; Bai, Harrison X; Sun, James; Neale, Natalie; Wu, Jing; Wang, Yinyan; Chang, Ken; Huang, Raymond Y; Zhang, Paul J; Li, Xuejun; Xiao, Bo; Cao, Ya; Tao, Yongguang; Yang, Li

2018-06-19

Lower-grade gliomas (LGGs, defined as WHO grades II and III) with 1p19q codeletion have increased chemosensitivity when compared to LGGs without 1p19q codeletion, but the mechanism is currently unknown. RNAseq data from 515 LGG patients in the Cancer Genome Atlas (TCGA) were analyzed to compare the effect of expression of the 9 DNA repair genes located on chromosome arms 1p and 19q on progression free survival (PFS) and overall survival (OS) between patients who received chemotherapy and those who did not. Chemosensitivity of cells with DNA repair genes knocked down was tested using MTS cell proliferation assay in HS683 cell line and U251 cell line. The expression of 9 DNA repair genes on 1p and 19q was significantly lower in 1p19q-codeleted tumors (n = 175) than in tumors without the codeletion (n = 337) (p < 0.001). In LGG patients who received chemotherapy, lower expression of LIG1, POLD1, PNKP, RAD54L and MUTYH was associated with longer PFS and OS. This difference between chemotherapy and non-chemotherapy groups in the association of gene expression with survival was not observed in non-DNA repair genes located on chromosome arms 1p and 19q. MTS assays showed that knockdown of DNA repair genes LIG1, POLD1, PNKP, RAD54L and MUTYH significantly inhibited recovery in response to temozolomide when compared with control group (p < 0.001). Our results suggest that reduced expression of DNA repair genes on chromosome arms 1p and 19q may account for the increased chemosensitivity of LGGs with 1p19q codeletion.

Structural insights into NHEJ: building up an integrated picture of the dynamic DSB repair super complex, one component and interaction at a time

PubMed Central

Williams, Gareth J.; Hammel, Michal; Radhakrishnan, Sarvan Kumar; Ramsden, Dale; Lees-Miller, Susan P.; Tainer, John A.

2014-01-01

Non-homologous end joining (NHEJ) is the major pathway for repair of DNA double-strand breaks (DSBs) in human cells. NHEJ is also needed for V(D)J recombination and the development of T and B cells in vertebrate immune systems, and acts in both the generation and prevention of non-homologous chromosomal translocations, a hallmark of genomic instability and many human cancers. X-ray crystal structures, cryo-electron microscopy envelopes, and small angle X-ray scattering (SAXS) solution conformations and assemblies are defining most of the core protein components for NHEJ: Ku70/Ku80 heterodimer; the DNA dependent protein kinase catalytic subunit (DNA-PKcs); the structure-specific endonuclease Artemis along with polynucleotide kinase/phosphatase (PNKP), aprataxin and PNKP related protein (APLF); the scaffolding proteins XRCC4 and XLF (XRCC4-like factor); DNA polymerases, and DNA ligase IV (Lig IV). The dynamic assembly of multi-protein NHEJ complexes at DSBs is regulated in part by protein phosphorylation. The basic steps of NHEJ have been biochemically defined to require: 1) DSB detection by the Ku heterodimer with subsequent DNA-PKcs tethering to form the DNA-PKcs-Ku-DNA complex (termed DNA-PK), 2) lesion processing, and 3) DNA end ligation by Lig IV, which functions in complex with XRCC4 and XLF. The current integration of structures by combined methods is resolving puzzles regarding the mechanisms, coordination and regulation of these three basic steps. Overall, structural results suggest the NHEJ system forms a flexing scaffold with the DNA-PKcs HEAT repeats acting as compressible macromolecular springs suitable to store and release conformational energy to apply forces to regulate NHEJ complexes and the DNA substrate for DNA end protection, processing, and ligation. PMID:24656613

Profound Climatic Effects on Two East Asian Black-Throated Tits (Ave: Aegithalidae), Revealed by Ecological Niche Models and Phylogeographic Analysis

PubMed Central

Wang, Wenjuan; Lin, Congtian; Gao, Bin; Yang, Xiaojun; Zhang, Zhengwang; Lei, Fumin

2011-01-01

Although a number of studies have assessed the effects of geological and climatic changes on species distributions in East Asian, we still have limited knowledge of how these changes have impacted avian species in south-western and southern China. Here, we aim to study paleo-climatic effects on an East Asian bird, two subspecies of black-throated tit (A. c. talifuensis–concinnus) with the combined analysis of phylogeography and Ecological Niche Models (ENMs). We sequenced three mitochondrial DNA markers from 32 populations (203 individuals) and used phylogenetic inferences to reconstruct the intra-specific relationships among haplotypes. Population genetic analyses were undertaken to gain insight into the demographic history of these populations. We used ENMs to predict the distribution of target species during three periods; last inter-glacial (LIG), last glacial maximum (LGM) and present. We found three highly supported, monophyletic MtDNA lineages and different historical demography among lineages in A. c. talifuensis–concinnus. These lineages formed a narrowly circumscribed intra-specific contact zone. The estimated times of lineage divergences were about 2.4 Ma and 0.32 Ma respectively. ENMs predictions were similar between present and LGM but substantially reduced during LIG. ENMs reconstructions and molecular dating suggest that Pleistocene climate changes had triggered and shaped the genetic structure of black-throated tit. Interestingly, in contrast to profound impacts of other glacial cycles, ENMs and phylogeographic analysis suggest that LGM had limited effect on these two subspecies. ENMs also suggest that Pleistocene climatic oscillations enabled the formation of the contact zone and thus support the refuge theory. PMID:22195047

Monitoring Spatial Patterns of Vegetation Phenology in AN Australian Tropical Transect Using Modis Evi

NASA Astrophysics Data System (ADS)

Ma, X.; Huete, A.; Yu, Q.; Davies, K.; Coupe, N. R.

2012-07-01

Phenology is receiving increasing interest in the area of climate change and vegetation adaptation to climate. The phenology of a landscape can be used as a key parameter in land surface models and dynamic global vegetation models to more accurately simulate carbon, water and energy exchanges between land cover and atmosphere. However, the characterisation of phenology is lacking in tropical savannas which cover more than 30% of global land area, and are highly vulnerable to climate change. The objective of this study is to investigate the spatial pattern of vegetation phenology along the Northern Australia Tropical Transect (NATT) where the major biomes are wet and dry tropical savannas. For this analysis we used more than 11 years Moderate Resolution Imaging Spectroradiometer (MODIS) Enhanced Vegetation Index (EVI) product from 2000 to 2011. Eight phenological metrics were derived: Start of Season (SOS), End of Season (EOS), Length of Season (LOS), Maximum EVI (MaxG), Minimum EVI (MinG), annual amplitude (AMP), large integral (LIG), and small integral (SIG) were generated for each year and each pixel. Our results showed there are significant spatial patterns and considerable interannual variations of vegetation phenology along the NATT study area. Generally speaking, vegetation growing season started and ended earlier in the north, and started and ended later in the south, resulting in a southward decrease of growing season length (LOS). Vegetation productivity, which was represented by annual integral EVI (LIG), showed a significant descending trend from the northern part of NATT to the southern part. Segmented regression analysis showed that there exists a distinguishable breakpoint along the latitudinal gradient, at least in terms of annual minimum EVI (EVI), which is located between 18.84°S to 20.04°S.

Phase-Sensitive Surface Plasmon Resonance Sensors: Recent Progress and Future Prospects

PubMed Central

Deng, Shijie; Wang, Peng; Yu, Xinglong

2017-01-01

Surface plasmon resonance (SPR) is an optical sensing technique that is capable of performing real-time, label-free and high-sensitivity monitoring of molecular interactions. SPR biosensors can be divided according to their operating principles into angle-, wavelength-, intensity- and phase-interrogated devices. With their complex optical configurations, phase-interrogated SPR sensors generally provide higher sensitivity and throughput, and have thus recently emerged as prominent biosensing devices. To date, several methods have been developed for SPR phase interrogation, including heterodyne detection, polarimetry, shear interferometry, spatial phase modulation interferometry and temporal phase modulation interferometry. This paper summarizes the fundamentals of phase-sensitive SPR sensing, reviews the available methods for phase interrogation of these sensors, and discusses the future prospects for and trends in the development of this technology. PMID:29206182

Molecular orientation of organic thin films on dielectric solid substrates: a phase-sensitive vibrational SFG study.

PubMed

Ge, Aimin; Peng, Qiling; Qiao, Lin; Yepuri, Nageshwar R; Darwish, Tamim A; Matsusaki, Michiya; Akashi, Mitsuru; Ye, Shen

2015-07-21

Broadband phase-sensitive vibrational sum frequency generation (SFG) spectroscopy was utilized to study the molecular orientation of molecules adsorbed on dielectric solid substrates. A gold thin film was employed to generate a SFG signal as a local oscillator (LO). To simplify the phase measurement, a self-assembled monolayer (SAM) of octadecyltrichlorosilane (OTS) was used as a standard sample for phase correction of the phase-sensitive SFG measurements on the solid/air interface. It was demonstrated that the absolute orientation of molecules in the LB films on a fused quartz surface can be clearly distinguished by phase-sensitive SFG measurement. In addition, the observation on the SAM of d35-OTS reveals that the two C-H stretching modes for α-CH2 group are in opposite phase. Furthermore, by using the present phase-sensitive SFG setup, the orientation flipping of water molecules on positively and negatively charged solid/liquid interface can be distinguished.

Word Frequency Analysis. MOS: 12C. Skill Levels 1 & 2.

DTIC Science & Technology

1981-05-01

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Effects of loss on the phase sensitivity with parity detection in an SU(1,1) interferometer

NASA Astrophysics Data System (ADS)

Li, Dong; Yuan, Chun-Hua; Yao, Yao; Jiang, Wei; Li, Mo; Zhang, Weiping

2018-05-01

We theoretically study the effects of loss on the phase sensitivity of an SU(1,1) interferometer with parity detection with various input states. We show that although the sensitivity of phase estimation decreases in the presence of loss, it can still beat the shot-noise limit with small loss. To examine the performance of parity detection, the comparison is performed among homodyne detection, intensity detection, and parity detection. Compared with homodyne detection and intensity detection, parity detection has a slight better optimal phase sensitivity in the absence of loss, but has a worse optimal phase sensitivity with a significant amount of loss with one-coherent state or coherent $\\otimes$ squeezed state input.

Comparison on batch anaerobic digestion of five different livestock manures and prediction of biochemical methane potential (BMP) using different statistical models.

PubMed

Kafle, Gopi Krishna; Chen, Lide

2016-02-01

There is a lack of literature reporting the methane potential of several livestock manures under the same anaerobic digestion conditions (same inoculum, temperature, time, and size of the digester). To the best of our knowledge, no previous study has reported biochemical methane potential (BMP) predicting models developed and evaluated by solely using at least five different livestock manure tests results. The goal of this study was to evaluate the BMP of five different livestock manures (dairy manure (DM), horse manure (HM), goat manure (GM), chicken manure (CM) and swine manure (SM)) and to predict the BMP using different statistical models. Nutrients of the digested different manures were also monitored. The BMP tests were conducted under mesophilic temperatures with a manure loading factor of 3.5g volatile solids (VS)/L and a feed to inoculum ratio (F/I) of 0.5. Single variable and multiple variable regression models were developed using manure total carbohydrate (TC), crude protein (CP), total fat (TF), lignin (LIG) and acid detergent fiber (ADF), and measured BMP data. Three different kinetic models (first order kinetic model, modified Gompertz model and Chen and Hashimoto model) were evaluated for BMP predictions. The BMPs of DM, HM, GM, CM and SM were measured to be 204, 155, 159, 259, and 323mL/g VS, respectively and the VS removals were calculated to be 58.6%, 52.9%, 46.4%, 81.4%, 81.4%, respectively. The technical digestion time (T80-90, time required to produce 80-90% of total biogas production) for DM, HM, GM, CM and SM was calculated to be in the ranges of 19-28, 27-37, 31-44, 13-18, 12-17days, respectively. The effluents from the HM showed the lowest nitrogen, phosphorus and potassium concentrations. The effluents from the CM digesters showed highest nitrogen and phosphorus concentrations and digested SM showed highest potassium concentration. Based on the results of the regression analysis, the model using the variable of LIG showed the best (R(2)=0.851, p=0.026) for BMP prediction among the single variable models, and the model including variables of TC and TF showed the best prediction for BMPs (R(2)=0.913, p=0.068-0.075) comparing with other two-variable models, while the model including variables of CP, LIG and ADF performed the best in BMP prediction (R(2)=0.999, p=0.009-0.017) if three-variable models were compared. Among the three kinetic models used, the first order kinetic model fitted the measured BMPs data best (R(2)=0.996-0.998, rRMSE=0.171-0.381) and deviations between measured and the first order kinetic model predicted BMPs were less than 3.0%. Published by Elsevier Ltd.

Stable isotope compositions of speleothems from the last interglacial - Spatial patterns of climate fluctuations in Europe

NASA Astrophysics Data System (ADS)

Demény, Attila; Kern, Zoltán; Czuppon, György; Németh, Alexandra; Leél-Őssy, Szabolcs; Siklósy, Zoltán; Lin, Ke; Hu, Hsun-Ming; Shen, Chuan-Chou; Vennemann, Torsten W.; Haszpra, László

2017-04-01

Studies on the last interglacial (LIG) can provide information on how our environment behaved in a period of slightly higher global temperatures at about 125 ± 4 ka, even if it is not the best analogue for the Holocene. The available LIG climate proxy records are usually better preserved and can be studied at a higher resolution than those of the preceding interglacials, allowing detailed comparisons. This paper presents complex stable hydrogen, carbon and oxygen isotope records obtained for carbonate (δ13C and δ18Ocarb) and fluid inclusion hosted water (δD and δ18Ow) of a stalagmite from the Baradla Cave system in Central Europe that covers most of the LIG, as proven by U-Th dates. Comparing its C and O isotope data with records reported for other speleothem (cave-hosted carbonate) deposits from Europe revealed the complex behavior of these climate proxies, with a concerted relative increase in 18O of carbonates from 128 to 120 ka and synchronized shifts in the opposite direction after 119 ka. The hydrogen isotope analyses of inclusion-hosted water extracted from the BAR-II stalagmite also correspond to the regional climate proxy records, with meaningful deviations from global temperature trends. Beside following the general paleotemperature pattern from the climate optimum (high δD values up to -64‰ around 120 ka) to the subsequent cooling starting at about 119 ka (low δD values down to -90‰ at about 109 ka), a period between 126.5 and 123 ka with low δD values (down to -81‰) is detected in the BAR-II stalagmite. Although the isotope shifts are muted in the C-O isotope data of carbonate due to competitive fractionation processes, the δ13C data show a positive relationship with the δD pattern, indicating humidity - and possibly temperature - variations. The periods with low δD values fit well to temperature and humidity changes inferred from proxy records from western Europe to the eastern Mediterranean. Spatial distributions of these variables show, that at about 125 ± 2 ka the Mediterranean region was characterized by warm, humid conditions and enhanced seasonality with elevated winter precipitation. The combined interpretation of stable isotope data revealed that the Alpine and Mediterranean regions behaved differently during Greenland Stadial 26 (GS26, ∼119 to 116.2 ka). While the Alpine records fluctuated in close agreement with the Central Greenland ice core δ18O data, the BAR-II stalagmite show a positive δ18Ocarb anomaly. The Baradla data indicate enhanced aridity and seasonality for a part of GS26, with the relative dominance of summer precipitation and Mediterranean moisture contribution. Following the GS26 event, the effect of long-term global cooling becomes dominant in the Baradla isotope records and leads to glacial inception at about 109 ka.

An Introduction to Phase-Sensitive Amplifiers: An Inexpensive Student Instrument

ERIC Educational Resources Information Center

Temple, Paul A.

1975-01-01

Discusses the principle of operation of phase-sensitive amplifiers. Gives three examples, suitable for undergraduate laboratory use, of the use of phase-sensitive, or "lock-in" amplifiers. Concludes with a description of an inexpensive lock-in amplifier which has an overall voltage gain of 1000. (Author/MLH)

Determination of Photoperiod-Sensitive Phase in Chickpea (Cicer arietinum L.)

PubMed Central

Daba, Ketema; Warkentin, Thomas D.; Bueckert, Rosalind; Todd, Christopher D.; Tar’an, Bunyamin

2016-01-01

Photoperiod is one of the major environmental factors determining time to flower initiation and first flower appearance in plants. In chickpea, photoperiod sensitivity, expressed as delayed to flower under short days (SD) as compared to long days (LD), may change with the growth stage of the crop. Photoperiod-sensitive and -insensitive phases were identified by experiments in which individual plants were reciprocally transferred in a time series from LD to SD and vice versa in growth chambers. Eight chickpea accessions with differing degrees of photoperiod sensitivity were grown in two separate chambers, one of which was adjusted to LD (16 h light/8 h dark) and the other adjusted to SD (10 h light/14 h dark), with temperatures of 22/16°C (12 h light/12 h dark) in both chambers. The accessions included day-neutral (ICCV 96029 and FLIP 98-142C), intermediate (ICC 15294, ICC 8621, ILC 1687, and ICC 8855), and photoperiod-sensitive (CDC Corinne and CDC Frontier) responses. Control plants were grown continuously under the respective photoperiods. Reciprocal transfers of plants between the SD and LD photoperiod treatments were made at seven time points after sowing, customized for each accession based on previous data. Photoperiod sensitivity was detected in intermediate and photoperiod-sensitive accessions. For the day-neutral accession, ICCV 96029, there was no significant difference in the number of days to flowering of the plants grown under SD and LD as well as subsequent transfers. In photoperiod-sensitive accessions, three different phenological phases were identified: a photoperiod-insensitive pre-inductive phase, a photoperiod-sensitive inductive phase, and a photoperiod-insensitive post-inductive phase. The photoperiod-sensitive phase extends after flower initiation to full flower development. Results from this research will help to develop cultivars with shorter pre-inductive photoperiod-insensitive and photoperiod-sensitive phases to fit to regions with short growing seasons. PMID:27148306

Phase-sensitive flow cytometer

DOEpatents

Steinkamp, John A.

1993-01-01

A phase-sensitive flow cytometer (FCM) provides additional FCM capability to use the fluorescence lifetime of one or more fluorochromes bound to single cells to provide additional information regarding the cells. The resulting fluorescence emission can be resolved into individual fluorescence signals if two fluorochromes are present or can be converted directly to a decay lifetime from a single fluorochrome. The excitation light for the fluorochromes is modulated to produce an amplitude modulated fluorescence pulse as the fluorochrome is excited in the FCM. The modulation signal also forms a reference signal that is phase-shifted a selected amount for subsequent mixing with the output modulated fluorescence intensity signal in phase-sensitive detection circuitry. The output from the phase-sensitive circuitry is then an individual resolved fluorochrome signal or a single fluorochrome decay lifetime, depending on the applied phase shifts.

Auditory cortical neurons are sensitive to static and continuously changing interaural phase cues.

PubMed

Reale, R A; Brugge, J F

1990-10-01

1. The interaural-phase-difference (IPD) sensitivity of single neurons in the primary auditory (AI) cortex of the anesthetized cat was studied at stimulus frequencies ranging from 120 to 2,500 Hz. Best frequencies of the 43 AI cells sensitive to IPD ranged from 190 to 2,400 Hz. 2. A static IPD was produced when a pair of low-frequency tone bursts, differing from one another only in starting phase, were presented dichotically. The resulting IPD-sensitivity curves, which plot the number of discharges evoked by the binaural signal as a function of IPD, were deeply modulated circular functions. IPD functions were analyzed for their mean vector length (r) and mean interaural phase (phi). Phase sensitivity was relatively independent of best frequency (BF) but highly dependent on stimulus frequency. Regardless of BF or stimulus frequency within the excitatory response area the majority of cells fired maximally when the ipsilateral tone lagged the contralateral signal and fired least when this interaural-phase relationship was reversed. 3. Sensitivity to continuously changing IPD was studied by delivering to the two ears 3-s tones that differed slightly in frequency, resulting in a binaural beat. Approximately 26% of the cells that showed a sensitivity to static changes in IPD also showed a sensitivity to dynamically changing IPD created by this binaural tonal combination. The discharges were highly periodic and tightly synchronized to a particular phase of the binaural beat cycle. High synchrony can be attributed to the fact that cortical neurons typically respond to an excitatory stimulus with but a single spike that is often precisely timed to stimulus onset. A period histogram, binned on the binaural beat frequency (fb), produced an equivalent IPD-sensitivity function for dynamically changing interaural phase. For neurons sensitive to both static and continuously changing interaural phase there was good correspondence between their static (phi s) and dynamic (phi d) mean interaural phases. 4. All cells responding to a dynamically changing stimulus exhibited a linear relationship between mean interaural phase and beat frequency. Most cells responded equally well to binaural beats regardless of the initial direction of phase change. For a fixed duration stimulus, and at relatively low fb, the number of spikes evoked increased with increasing fb, reflecting the increasing number of effective stimulus cycles. At higher fb, AI neurons were unable to follow the rate at which the most effective phase repeated itself during the 3 s of stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Study of Nonclassical Fields in Phase-Sensitive Reservoirs

NASA Technical Reports Server (NTRS)

Kim, Myung Shik; Imoto, Nobuyuki

1996-01-01

We show that the reservoir influence can be modeled by an infinite array of beam splitters. The superposition of the input fields in the beam splitter is discussed with the convolution laws for their quasiprobabilities. We derive the Fokker-Planck equation for the cavity field coupled with a phase-sensitive reservoir using the convolution law. We also analyze the amplification in the phase-sensitive reservoir with use of the modified beam splitter model. We show the similarities and differences between the dissipation and amplification models. We show that a super-Poissonian input field cannot become sub-Poissonian by the phase-sensitive amplification.

Capillary electrophoresis-electrospray ionization-mass spectrometry method to determine the phenolic fraction of extra-virgin olive oil.

PubMed

Carrasco-Pancorbo, Alegría; Arráez-Román, David; Segura-Carretero, Antonio; Fernández-Gutiérrez, Alberto

2006-06-01

We describe the first analytical method involving SPE and CZE coupled to ESI-IT MS (CZE-ESI-MS) used to identify and characterize phenolic compounds in olive oil samples. The SPE, CZE and ESI-MS parameters were optimized in order to maximize the number of phenolic compounds detected and the sensitivity of their determination. To this end we have devised a detailed method to find the best conditions for CE separation and the detection by MS of the phenolic compounds present in olive oil using a methanol-water extract of Picual extra-virgin olive oil (VOO). Electrophoretic separation was carried out using an aqueous CE buffer system consisting of 60 mM NH(4)OAc at pH 9.5 with 5% of 2-propanol, a sheath liquid containing 2-propanol/water 60:40 v/v and 0.1% v/v triethylamine. This method offers to the analyst the chance to study important phenolic compounds such as phenolic alcohols (tyrosol (TY), hydroxytyrosol (HYTY) and 2-(4-hydroxyphenyl)ethyl acetate), lignans ((+)-pinoresinol and (+)-1-acetoxypinoresinol), complex phenols (ligstroside aglycon (Lig Agl), oleuropein aglycon, their respective decarboxylated derivatives and several isomeric forms of these (dialdehydic form of oleuropein aglycon, dialdehydic form of ligstroside aglycon, dialdehydic form of decarboxymethyl elenolic acid linked to HYTY, dialdehydic form of decarboxymethyl elenolic acid linked to TY) and 10-hydroxy-oleuropein aglycon) and one other phenolic compound (elenolic acid) in extra-VOO by using a simple SPE before CE-ESI-MS analysis.

Impurities in Tc-99m radiopharmaceutical solution obtained from Mo-100 in cyclotron.

PubMed

Tymiński, Zbigniew; Saganowski, Paweł; Kołakowska, Ewa; Listkowska, Anna; Ziemek, Tomasz; Cacko, Daniel; Dziel, Tomasz

2018-04-01

The gamma emitting impurities in 99m Tc solution obtained from enriched molybdenum 100 Mo metallic target after its irradiation in a cyclotron were measured using a high-purity germanium (HPGe) detector. The radioactivity range of tested samples of 99m Tc was rather low, in the range from 0.34 to 2.39 MBq, thus creating a challenge to investigate the standard measurement HPGe system for impurity detection and quantification. In the process of 99m Tc separation from irradiated target the AnaLig® Tc-02 resin, Dionex H + and Alumina A columns were used. Fractions of eluates from various steps of separation process were taken and measured for radionuclidic purity. The overall measurement sensitivity of gamma emitters in terms of minimum detectable activity (MDA) was found at the level of 14-70Bq with emission lines in range of 36 - 1836keV resulting in impurity content range of 6.7 × 10 -4 to 3.4 × 10 -3 % for 93 Tc, 93m Tc, 94 Tc, 94m Tc, 95 Tc, 95m Tc, 96 Tc 96 Nb, 97 Nb, 99 Mo contaminants and 9.4 × 10 -3 % for 97m Tc. The usefulness of the chosen measurement conditions and the method applied to testing the potential contaminators was proved by reaching satisfactory results of MDAs less than the criteria of impurity concentration of all nuclides specified in the European Pharmacopoeia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Improved detection sensitivity of D-mannitol crystalline phase content using differential spectral phase shift terahertz spectroscopy measurements.

PubMed

Allard, Jean-François; Cornet, Alain; Debacq, Christophe; Meurens, Marc; Houde, Daniel; Morris, Denis

2011-02-28

We report quantitative measurement of the relative proportion of δ- and β-D-mannitol crystalline phases inserted into polyethylene powder pellets, obtained by time-domain terahertz spectroscopy. Nine absorption bands have been identified from 0.2 THz to 2.2 THz. The best quantification of the δ-phase proportion is made using the 1.01 THz absorption band. Coherent detection allows using the spectral phase shift of the transmitted THz waveform to improve the detection sensitivity of the relative δ-phase proportion. We argue that differential phase shift measurements are less sensitive to samples' defects. Using a linear phase shift compensation for pellets of slightly different thicknesses, we were able to distinguish a 0.5% variation in δ-phase proportion.

Phase-sensitive flow cytometer

DOEpatents

Steinkamp, J.A.

1993-12-14

A phase-sensitive flow cytometer (FCM) provides additional FCM capability to use the fluorescence lifetime of one or more fluorochromes bound to single cells to provide additional information regarding the cells. The resulting fluorescence emission can be resolved into individual fluorescence signals if two fluorochromes are present or can be converted directly to a decay lifetime from a single fluorochrome. The excitation light for the fluorochromes is modulated to produce an amplitude modulated fluorescence pulse as the fluorochrome is excited in the FCM. The modulation signal also forms a reference signal that is phase-shifted a selected amount for subsequent mixing with the output modulated fluorescence intensity signal in phase-sensitive detection circuitry. The output from the phase-sensitive circuitry is then an individual resolved fluorochrome signal or a single fluorochrome decay lifetime, depending on the applied phase shifts. 15 figures.

Phase sensitive optical coherence microscopy for photothermal imaging of gold nanorods

NASA Astrophysics Data System (ADS)

Hu, Yong; Podoleanu, Adrian G.; Dobre, George

2018-03-01

We describe a swept source based phase sensitive optical coherence microscopy (OCM) system for photothermal imaging of gold nanorods (GNR). The phase sensitive OCM system employed in the study has a displacement sensitivity of 0.17 nm to vibrations at single frequencies below 250 Hz. We demonstrate the generation of phase maps and confocal phase images. By displaying the difference between successive confocal phase images, we perform the confocal photothermal imaging of accumulated GNRs behind a glass coverslip and behind the scattering media separately. Compared with two-photon luminescence (TPL) detection techniques reported in literature, the technique in this study has the advantage of a simplified experimental setup and provides a more efficient method for imaging the aggregation of GNR. However, the repeatability performance of this technique suffers due to jitter noise from the swept laser source.

Tunable sensitivity phase detection of transmitted-type dual-channel guided-mode resonance sensor based on phase-shift interferometry.

PubMed

Kuo, Wen-Kai; Syu, Siang-He; Lin, Peng-Zhi; Yu, Hsin Her

2016-02-01

This paper reports on a transmitted-type dual-channel guided-mode resonance (GMR) sensor system that uses phase-shifting interferometry (PSI) to achieve tunable phase detection sensitivity. Five interference images are captured for the PSI phase calculation within ∼15  s by using a liquid crystal retarder and a USB web camera. The GMR sensor structure is formed by a nanoimprinting process, and the dual-channel sensor device structure for molding is fabricated using a 3D printer. By changing the rotation angle of the analyzer in front of the camera in the PSI system, the sensor detection sensitivity can be tuned. The proposed system may achieve high throughput as well as high sensitivity. The experimental results show that an optimal detection sensitivity of 6.82×10(-4)  RIU can be achieved.

Staffing Cyber Operations (Briefing Charts)

DTIC Science & Technology

2015-05-01

Ti tle 1 0 m is si on s  N o tim e to b ui ld th is re qu ire m en t i n th e P O M – R eq ui re m...o r f ro m a co or di na te d m ili ta ry o pe ra tio n of w hi ch th at a ct c on st itu te s an in te gr al p ar t  B el lig er en t...U se d C A P E F C oM To ol ; a dj us te d so m e fa ct or s  S ub st itu

Thermal Coefficient of Linear Expansion Modified by Dendritic Segregation in Nickel-Iron Alloys

NASA Astrophysics Data System (ADS)

Ogorodnikova, O. M.; Maksimova, E. V.

2018-05-01

The paper presents investigations of thermal properties of Fe-Ni and Fe-Ni-Co casting alloys affected by the heterogeneous distribution of their chemical elements. It is shown that nickel dendritic segregation has a negative effect on properties of studied invars. A mathematical model is proposed to explore the influence of nickel dendritic segregation on the thermal coefficient of linear expansion (TCLE) of the alloy. A computer simulation of TCLE of Fe-Ni-Co superinvars is performed with regard to a heterogeneous distribution of their chemical elements over the whole volume. The ProLigSol computer software application is developed for processing the data array and results of computer simulation.

Combining Monte Carlo methods with coherent wave optics for the simulation of phase-sensitive X-ray imaging

PubMed Central

Peter, Silvia; Modregger, Peter; Fix, Michael K.; Volken, Werner; Frei, Daniel; Manser, Peter; Stampanoni, Marco

2014-01-01

Phase-sensitive X-ray imaging shows a high sensitivity towards electron density variations, making it well suited for imaging of soft tissue matter. However, there are still open questions about the details of the image formation process. Here, a framework for numerical simulations of phase-sensitive X-ray imaging is presented, which takes both particle- and wave-like properties of X-rays into consideration. A split approach is presented where we combine a Monte Carlo method (MC) based sample part with a wave optics simulation based propagation part, leading to a framework that takes both particle- and wave-like properties into account. The framework can be adapted to different phase-sensitive imaging methods and has been validated through comparisons with experiments for grating interferometry and propagation-based imaging. The validation of the framework shows that the combination of wave optics and MC has been successfully implemented and yields good agreement between measurements and simulations. This demonstrates that the physical processes relevant for developing a deeper understanding of scattering in the context of phase-sensitive imaging are modelled in a sufficiently accurate manner. The framework can be used for the simulation of phase-sensitive X-ray imaging, for instance for the simulation of grating interferometry or propagation-based imaging. PMID:24763652

Apomorphine conditioning and sensitization: the paired/unpaired treatment order as a new major determinant of drug conditioned and sensitization effects.

PubMed

de Matos, Liana Wermelinger; Carey, Robert J; Carrera, Marinete Pinheiro

2010-09-01

Repeated treatments with psychostimulant drugs generate behavioral sensitization. In the present study we employed a paired/unpaired protocol to assess the effects of repeated apomorphine (2.0 mg/kg) treatments upon locomotion behavior. In the first experiment we assessed the effects of conditioning upon apomorphine sensitization. Neither the extinction of the conditioned response nor a counter-conditioning procedure in which we paired an inhibitory treatment (apomorphine 0.05 mg/kg) with the previously established conditioned stimulus modified the sensitization response. In the second experiment, we administered the paired/unpaired protocol in two phases. In the second phase, we reversed the paired/unpaired protocol. Following the first phase, the paired group alone exhibited conditioned locomotion in the vehicle test and a sensitization response. In the second phase, the initial unpaired group which received 5 paired apomorphine trials during the reversal phase did not develop a conditioned response but developed a potentiated sensitization response. This disassociation of the conditioned response from the sensitization response is attributed to an apomorphine anti-habituation effect that can generate a false positive Pavlovian conditioned response effect. The potentiated sensitization response induced by the treatment reversal protocol points to an important role for the sequential experience of the paired/unpaired protocol in behavioral sensitization. 2010 Elsevier Inc. All rights reserved.

Ion Exchange Distribution Coefficient Tests and Computer Modeling at High Ionic Strength Supporting Technetium Removal Resin Maturation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nash, Charles A.; Hamm, L. Larry; Smith, Frank G.

2014-12-19

The primary treatment of the tank waste at the DOE Hanford site will be done in the Waste Treatment and Immobilization Plant (WTP) that is currently under construction. The baseline plan for this facility is to treat the waste, splitting it into High Level Waste (HLW) and Low Activity Waste (LAW). Both waste streams are then separately vitrified as glass and poured into canisters for disposition. The LAW glass will be disposed onsite in the Integrated Disposal Facility (IDF). There are currently no plans to treat the waste to remove technetium, so its disposition path is the LAW glass. Duemore » to the water solubility properties of pertechnetate and long half-life of 99Tc, effective management of 99Tc is important to the overall success of the Hanford River Protection Project mission. To achieve the full target WTP throughput, additional LAW immobilization capacity is needed, and options are being explored to immobilize the supplemental LAW portion of the tank waste. Removal of 99Tc, followed by off-site disposal, would eliminate a key risk contributor for the IDF Performance Assessment (PA) for supplemental waste forms, and has potential to reduce treatment and disposal costs. Washington River Protection Solutions (WRPS) is developing some conceptual flow sheets for supplemental LAW treatment and disposal that could benefit from technetium removal. One of these flowsheets will specifically examine removing 99Tc from the LAW feed stream to supplemental immobilization. To enable an informed decision regarding the viability of technetium removal, further maturation of available technologies is being performed. This report contains results of experimental ion exchange distribution coefficient testing and computer modeling using the resin SuperLig ® 639 a to selectively remove perrhenate from high ionic strength simulated LAW. It is advantageous to operate at higher concentration in order to treat the waste stream without dilution and to minimize the volume of the final wasteform. This work examined the impact of high ionic strength, high density, and high viscosity if higher concentration LAW feed solution is used. Perrhenate (ReO 4 -) has been shown to be a good nonradioactive surrogate for pertechnetate in laboratory testing for this ion exchange resin, and the performance bias is well established. Equilibrium contact testing with 7.8 M [Na +] average simulant concentrations indicated that the SuperLig ® 639 resin average perrhenate distribution coefficient was 368 mL/g at a 100:1 phase ratio. Although this indicates good performance at high ionic strength, an equilibrium test cannot examine the impact of liquid viscosity, which impacts the diffusivity of ions and therefore the loading kinetics. To get an understanding of the effect of diffusivity, modeling was performed, which will be followed up with column tests in the future.« less

Neuro-genetic system for optimization of GMI samples sensitivity.

PubMed

Pitta Botelho, A C O; Vellasco, M M B R; Hall Barbosa, C R; Costa Silva, E

2016-03-01

Magnetic sensors are largely used in several engineering areas. Among them, magnetic sensors based on the Giant Magnetoimpedance (GMI) effect are a new family of magnetic sensing devices that have a huge potential for applications involving measurements of ultra-weak magnetic fields. The sensitivity of magnetometers is directly associated with the sensitivity of their sensing elements. The GMI effect is characterized by a large variation of the impedance (magnitude and phase) of a ferromagnetic sample, when subjected to a magnetic field. Recent studies have shown that phase-based GMI magnetometers have the potential to increase the sensitivity by about 100 times. The sensitivity of GMI samples depends on several parameters, such as sample length, external magnetic field, DC level and frequency of the excitation current. However, this dependency is yet to be sufficiently well-modeled in quantitative terms. So, the search for the set of parameters that optimizes the samples sensitivity is usually empirical and very time consuming. This paper deals with this problem by proposing a new neuro-genetic system aimed at maximizing the impedance phase sensitivity of GMI samples. A Multi-Layer Perceptron (MLP) Neural Network is used to model the impedance phase and a Genetic Algorithm uses the information provided by the neural network to determine which set of parameters maximizes the impedance phase sensitivity. The results obtained with a data set composed of four different GMI sample lengths demonstrate that the neuro-genetic system is able to correctly and automatically determine the set of conditioning parameters responsible for maximizing their phase sensitivities. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Expression changes of major outer membrane protein antigens in Leptospira interrogans during infection and its mechanism].

PubMed

Zheng, Linli; Ge, Yumei; Hu, Weilin; Yan, Jie

2013-03-01

To determine expression changes of major outer membrane protein(OMP) antigens of Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai strain Lai during infection of human macrophages and its mechanism. OmpR encoding genes and OmpR-related histidine kinase (HK) encoding gene of L.interrogans strain Lai and their functional domains were predicted using bioinformatics technique. mRNA level changes of the leptospiral major OMP-encoding genes before and after infection of human THP-1 macrophages were detected by real-time fluorescence quantitative RT-PCR. Effects of the OmpR-encoding genes and HK-encoding gene on the expression of leptospiral OMPs during infection were determined by HK-peptide antiserum block assay and closantel inhibitive assays. The bioinformatics analysis indicated that LB015 and LB333 were referred to OmpR-encoding genes of the spirochete, while LB014 might act as a OmpR-related HK-encoding gene. After the spirochete infecting THP-1 cells, mRNA levels of leptospiral lipL21, lipL32 and lipL41 genes were rapidly and persistently down-regulated (P <0.01), whereas mRNA levels of leptospiral groEL, mce, loa22 and ligB genes were rapidly but transiently up-regulated (P<0.01). The treatment with closantel and HK-peptide antiserum partly reversed the infection-based down-regulated mRNA levels of lipL21 and lipL48 genes (P <0.01). Moreover, closantel caused a decrease of the infection-based up-regulated mRNA levels of groEL, mce, loa22 and ligB genes (P <0.01). Expression levels of L.interrogans strain Lai major OMP antigens present notable changes during infection of human macrophages. There is a group of OmpR-and HK-encoding genes which may play a major role in down-regulation of expression levels of partial OMP antigens during infection.

Study of collisional deactivation of O{sub 2}(b{sup 1}{Sigma}{sub g}{sup +}) molecules in a hydrogen-oxygen mixture at high temperatures using laser-induced gratings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kozlov, D. N., E-mail: dnk@kapella.gpi.ru; Kobtsev, V. D.; Stel'makh, O. M.

2013-07-15

Collisional deactivation of O{sub 2}(b{sup 1}{Sigma}{sub g}{sup +}) molecules resonantly excited by a 10 ns pulse of laser radiation with a wavelength of 762 nm in H{sub 2}/O{sub 2} mixtures is experimentally studied. The radiation intensity and hence the molecule excitation efficiency have a spatially periodic modulation that leads to the formation of laser-induced gratings (LIGs) of the refractive index. The study of LIG temporal evolution allows collisional relaxation rates of molecular excited states and gas temperature to be determined. In this work, the b{sup 1}{Sigma}{sub g}{sup +} state of O{sub 2} molecules deactivation rates are measured in a 4.3more » vol % H{sub 2} mixture at the number density of 2 amg in the temperature range 291-850 K. The physical deactivation is shown to dominate in the collisions of H{sub 2} with O{sub 2}(b{sup 1}{Sigma}{sub g}{sup +}) and O{sub 2}(a{sup 1}{Delta}{sub g}) up to temperatures of 780-790 K at time delays up to 10 {mu}s after the excitation pulse. The parameters of the obtained temperature dependence of the (b{sup 1}{Sigma}{sub g}{sup +} state deactivation rate agree well with the data of independent measurements performed earlier at lower temperatures (200-400 K). Tunable diode laser absorption spectroscopy is used to measure the temperature dependence of the number density of the H{sub 2}O molecules which appear as the mixture, as the result of the dark gross reaction with O{sub 2} molecules in the ground state, O{sub 2} + 2H{sub 2} {yields} 2H{sub 2}O. The measurements show that this reaction results in complete transformation of H{sub 2} into H{sub 2}O at temperatures of 790-810 K.« less

Phase sensitivity of fundamental mode to external atmospheric pressure for hollow-core photonic bandgap fiber

NASA Astrophysics Data System (ADS)

Xu, Xiaobin; Liu, Yangqian; Gao, Fuyu; Song, Ningfang

2018-07-01

Hollow-core photonic bandgap fibers (HC-PBFs) are suitable for spaceborne fiber optical gyroscopes owing to their excellent environmental adaptability. However, hundreds of small holes full of air at one atmosphere of pressure can make the HC-PBF sensitive to external atmospheric pressure. In this study, we investigated the phase sensitivity of the fundamental mode to external atmospheric pressure for the HC-PBF, and the experimental result indicates that the phase sensitivity is approximately 1.6 × 10-5 ppm/Pa, which is mostly contributed by the change in the pressure-induced length. Through the choice of coating, the phase sensitivity to external atmospheric pressure can be reduced by about a factor of five compared to current HC-PBFs, and the excellent temperature performance can be maintained at the same time.

Projection-based estimation and nonuniformity correction of sensitivity profiles in phased-array surface coils.

PubMed

Yun, Sungdae; Kyriakos, Walid E; Chung, Jun-Young; Han, Yeji; Yoo, Seung-Schik; Park, Hyunwook

2007-03-01

To develop a novel approach for calculating the accurate sensitivity profiles of phased-array coils, resulting in correction of nonuniform intensity in parallel MRI. The proposed intensity-correction method estimates the accurate sensitivity profile of each channel of the phased-array coil. The sensitivity profile is estimated by fitting a nonlinear curve to every projection view through the imaged object. The nonlinear curve-fitting efficiently obtains the low-frequency sensitivity profile by eliminating the high-frequency image contents. Filtered back-projection (FBP) is then used to compute the estimates of the sensitivity profile of each channel. The method was applied to both phantom and brain images acquired from the phased-array coil. Intensity-corrected images from the proposed method had more uniform intensity than those obtained by the commonly used sum-of-squares (SOS) approach. With the use of the proposed correction method, the intensity variation was reduced to 6.1% from 13.1% of the SOS. When the proposed approach was applied to the computation of the sensitivity maps during sensitivity encoding (SENSE) reconstruction, it outperformed the SOS approach in terms of the reconstructed image uniformity. The proposed method is more effective at correcting the intensity nonuniformity of phased-array surface-coil images than the conventional SOS method. In addition, the method was shown to be resilient to noise and was successfully applied for image reconstruction in parallel imaging.

Soluble Mesothelin Related Peptide (SMRP) and Osteopontin (OPN) as Early Detection Markers for Malignant Mesothelioma (MM) — EDRN Public Portal

Cancer.gov

Phase I: - Identification and assemblage of representative cohorts of individuals with MM, no malignancies but increased risk for MM due to asbestos exposure, and (optionally) lung malignancies other than MM Phase II (A) - Determine the sensitivity and specificity of SMRP and OPN in distinguishing individuals with a clinical diagnosis of malignant mesothelioma from individuals who are asbestos-exposed but without a clinical diagnosis of malignant mesothelioma. Phase II (B) – Determine the comparability of analyte values across contributing centers and determine covariates that influence analyte levels Phase II (C) – Determine the sensitivity and specificity of SMRP and OPN, alone and in combination, in distinguishing individuals with MM from those without. Phase III. Determine the sensitivity and specificity of SMRP and OPN in distinguishing individuals who would subsequently develop malignant mesothelioma from matched individuals who did not subsequently develop malignant mesothelioma. Phase IV. Determine the sensitivity and specificity of SMRP and OPN in other populations of interest.

Environmental Stress Induces Trinucleotide Repeat Mutagenesis in Human Cells by Alt-Nonhomologous End Joining Repair.

PubMed

Chatterjee, Nimrat; Lin, Yunfu; Yotnda, Patricia; Wilson, John H

2016-07-31

Multiple pathways modulate the dynamic mutability of trinucleotide repeats (TNRs), which are implicated in neurodegenerative disease and evolution. Recently, we reported that environmental stresses induce TNR mutagenesis via stress responses and rereplication, with more than 50% of mutants carrying deletions or insertions-molecular signatures of DNA double-strand break repair. We now show that knockdown of alt-nonhomologous end joining (alt-NHEJ) components-XRCC1, LIG3, and PARP1-suppresses stress-induced TNR mutagenesis, in contrast to the components of homologous recombination and NHEJ, which have no effect. Thus, alt-NHEJ, which contributes to genetic mutability in cancer cells, also plays a novel role in environmental stress-induced TNR mutagenesis. Published by Elsevier Ltd.

Sensitivity of a fibre scattered-light interferometer to external phase perturbations in an optical fibre

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alekseev, A E; Potapov, V T; Gorshkov, B G

2015-10-31

Sensitivity of a fibre scattered-light interferometer to external phase perturbations is studied for the first time. An expression is derived for an average power of a useful signal at the interferometer output under external harmonic perturbations in a signal fibre of the interferometer. It is shown that the maximum sensitivity of the scattered-light interferometer depends on the dispersion of the interferogram intensity. An average signal-to-noise ratio is determined theoretically and experimentally at the output of the interferometer at different amplitudes of external perturbations. Using the measured dependences of the signal-to-noise ratio, the threshold sensitivity of the fibre scattered-light interferometer tomore » external phase perturbations is found. The results obtained can be used to optimise characteristics of optical time-domain reflectometers and to design individual phase-sensitive fibre-optic sensors. (laser applications and other topics in quantum electronics)« less

Intergrated Systems Biology Approach for Ovarian Cancer Biomarker Discovery — EDRN Public Portal

Cancer.gov

The overall objective is to validate serum protein markers for early diagnosis of ovarian cancer with the ultimate goal being to develop a multiparametric panel consisting of 2-4 novel markers with 10 known markers for phase 3 analysis. In phase 1, we will screen for markers able to pass a threshold of 98% specificity and 30% sensitivity in a cohort of 300 women. Markers that pass phase 1 validation will be investigated in a phase 2 PRoBE cohort with a 98% specificity and 70% sensitivity cut-off. Finally, markers that pass phase 2 validation will be evaluated in EDRN CVC laboratory specimens with a cut-off of > 98% specificity and 90% sensitivity.

Mechanical modulation method for ultrasensitive phase measurements in photonics biosensing.

PubMed

Patskovsky, S; Maisonneuve, M; Meunier, M; Kabashin, A V

2008-12-22

A novel polarimetry methodology for phase-sensitive measurements in single reflection geometry is proposed for applications in optical transduction-based biological sensing. The methodology uses altering step-like chopper-based mechanical phase modulation for orthogonal s- and p- polarizations of light reflected from the sensing interface and the extraction of phase information at different harmonics of the modulation. We show that even under a relatively simple experimental arrangement, the methodology provides the resolution of phase measurements as low as 0.007 deg. We also examine the proposed approach using Total Internal Reflection (TIR) and Surface Plasmon Resonance (SPR) geometries. For TIR geometry, the response appears to be strongly dependent on the prism material with the best values for high refractive index Si. The detection limit for Si-based TIR is estimated as 10(-5) in terms Refractive Index Units (RIU) change. SPR geometry offers much stronger phase response due to a much sharper phase characteristics. With the detection limit of 3.2*10(-7) RIU, the proposed methodology provides one of best sensitivities for phase-sensitive SPR devices. Advantages of the proposed method include high sensitivity, simplicity of experimental setup and noise immunity as a result of a high stability modulation.

GLUCOCORTICOIDS AND CELLULAR IMMUNITY IN VITRO

PubMed Central

Cohen, Irun R.; Stavy, Lary; Feldman, Michael

1970-01-01

We studied the influence of glucocorticoids on the sensitization phase as well as on the cytolytic effector phase of an in vitro lymphocyte-mediated immune reaction. Lymphocytes obtained from the spleens or lymph nodes of unimmunized inbred rats were sensitized against foreign rat or mouse embryonic fibroblasts in cell culture. The capacity of the sensitized lymphocytes to produce a cytolytic effect was tested by transferring them to target fibroblast cultures. Injury to target fibroblasts was measured by release of radioactive 51Cr from previously labeled fibroblasts or by direct count of viable fibroblasts after incubation with sensitized lymphocytes. Various concentrations of water-soluble hydrocortisone or prednisolone were added to cell cultures during the 5 day sensitization phase and/or during the subsequent cytolytic effector phase and the influence of these hormones on the number and cytolytic capacity of the lymphocytes was measured. During the sensitization phase, the presence of glucocorticoid hormones, at concentrations of about 1 µg/ml, led to a profound decrease in the total number of recoverable lymphocytes. However, the per cent of large transformed lymphocytes was much greater in these treated cultures. The antigen-specific cytolytic capacity per cell of the glucocorticoid-treated lymphocytes, after the hormone was removed, was several times greater than that of lymphocytes sensitized in the absence of added hormones. Glucocorticoids influenced the effector phase of the reaction by inhibiting lymphocyte-mediated injury to target fibroblasts. The hormones, at concentrations of about 1 µg/ml, inhibited the cytolytic effect by about 50% without reducing the viability of the sensitized lymphocytes. Dose-dependent toxicity to lymphocytes and increasing inhibition of cytolytic effect appeared at higher concentrations of hormones. Thus, hydrocortisone and prednisolone, at concentrations of about 1 µg/ml, did not suppress the induction of sensitization, a process which they seem to facilitate in vitro. However, similar concentrations of these hormones appear to inhibit the cytolytic effector mechanism of sensitized lymphocytes. These findings may be relevant to the use of glucocorticoids as immunosuppressive agents in vivo. PMID:5511566

Phase modulation for reduced vibration sensitivity in laser-cooled clocks in space

NASA Technical Reports Server (NTRS)

Klipstein, W.; Dick, G.; Jefferts, S.; Walls, F.

2001-01-01

The standard interrogation technique in atomic beam clocks is square-wave frequency modulation (SWFM), which suffers a first order sensitivity to vibrations as changes in the transit time of the atoms translates to perceived frequency errors. Square-wave phase modulation (SWPM) interrogation eliminates sensitivity to this noise.

First demonstration of high-order QAM signal amplification in PPLN-based phase sensitive amplifier.

PubMed

Umeki, T; Tadanaga, O; Asobe, M; Miyamoto, Y; Takenouchi, H

2014-02-10

We demonstrate the phase sensitive amplification of a high-order quadrature amplitude modulation (QAM) signal using non-degenerate parametric amplification in a periodically poled lithium niobate (PPLN) waveguide. The interaction between the pump, signal, and phase-conjugated idler enables us to amplify arbitrary phase components of the signal. The 16QAM signals are amplified without distortion because of the high gain linearity of the PPLN-based phase sensitive amplifier (PSA). Both the phase and amplitude noise reduction capabilities of the PSA are ensured. Phase noise cancellation is achieved by using the interaction with the phase-conjugated idler. A degraded signal-to-noise ratio (SNR) is restored by using the gain difference between a phase-correlated signal-idler pair and uncorrelated excess noise. The applicability of the simultaneous amplification of multi-carrier signals and the amplification of two independent polarization signals are also confirmed with a view to realizing ultra-high spectrally efficient signal amplification.

Digital multi-channel stabilization of four-mode phase-sensitive parametric multicasting.

PubMed

Liu, Lan; Tong, Zhi; Wiberg, Andreas O J; Kuo, Bill P P; Myslivets, Evgeny; Alic, Nikola; Radic, Stojan

2014-07-28

Stable four-mode phase-sensitive (4MPS) process was investigated as a means to enhance two-pump driven parametric multicasting conversion efficiency (CE) and signal to noise ratio (SNR). Instability of multi-beam, phase sensitive (PS) device that inherently behaves as an interferometer, with output subject to ambient induced fluctuations, was addressed theoretically and experimentally. A new stabilization technique that controls phases of three input waves of the 4MPS multicaster and maximizes CE was developed and described. Stabilization relies on digital phase-locked loop (DPLL) specifically was developed to control pump phases to guarantee stable 4MPS operation that is independent of environmental fluctuations. The technique also controls a single (signal) input phase to optimize the PS-induced improvement of the CE and SNR. The new, continuous-operation DPLL has allowed for fully stabilized PS parametric broadband multicasting, demonstrating CE improvement over 20 signal copies in excess of 10 dB.

High sensitivity phase retrieval method in grating-based x-ray phase contrast imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Zhao; Gao, Kun; Chen, Jian

2015-02-15

Purpose: Grating-based x-ray phase contrast imaging is considered as one of the most promising techniques for future medical imaging. Many different methods have been developed to retrieve phase signal, among which the phase stepping (PS) method is widely used. However, further practical implementations are hindered, due to its complex scanning mode and high radiation dose. In contrast, the reverse projection (RP) method is a novel fast and low dose extraction approach. In this contribution, the authors present a quantitative analysis of the noise properties of the refraction signals retrieved by the two methods and compare their sensitivities. Methods: Using themore » error propagation formula, the authors analyze theoretically the signal-to-noise ratios (SNRs) of the refraction images retrieved by the two methods. Then, the sensitivities of the two extraction methods are compared under an identical exposure dose. Numerical experiments are performed to validate the theoretical results and provide some quantitative insight. Results: The SNRs of the two methods are both dependent on the system parameters, but in different ways. Comparison between their sensitivities reveals that for the refraction signal, the RP method possesses a higher sensitivity, especially in the case of high visibility and/or at the edge of the object. Conclusions: Compared with the PS method, the RP method has a superior sensitivity and provides refraction images with a higher SNR. Therefore, one can obtain highly sensitive refraction images in grating-based phase contrast imaging. This is very important for future preclinical and clinical implementations.« less

Demonstration of digital phase-sensitive boosting to extend signal reach for long-haul WDM systems using optical phase-conjugated copy.

PubMed

Tian, Yue; Huang, Yue-Kai; Zhang, Shaoliang; Prucnal, Paul R; Wang, Ting

2013-02-25

We demonstrate a hybrid optical/digital phase-sensitive boosting (PSB) technique for long-haul wavelength division multiplexing (WDM) transmission systems. The approach uses four-wave mixing (FWM) to generate a phase-conjugated idler alongside the original signal. At the receiver, the signal and idler are jointly detected, and the phases of the idler symbols are conjugated and summed with the signal symbols to suppress noise and nonlinear phase distortion. The proposed hybrid PSB scheme is independent of modulation format and does not require an optical phase-locked loop to achieve phase matching required by conventional phase-sensitive amplifiers. Our simulation and experimental results of 112-Gb/s dual-polarization quadrature phase-shift-keying (DP-QPSK) transmission confirmed the principle of the PSB scheme, attaining a Q-factor improvement of 2.4 dB over conventional single-channel transmission after 4,800 km of dispersion-managed fiber (DMF) link at the expense of 50% reduction in spectral efficiency and extending the system reach by 60% to 7,680 km.

Multiplexed highly sensitive detections of cancer biomarkers in thermal space using encapsulated phase change nanoparticles

NASA Astrophysics Data System (ADS)

Ma, Liyuan; Hong, Yan; Ma, Zeyu; Kaittanis, Charalambos; Perez, J. Manuel; Su, Ming

2009-07-01

We describe a multiplexed highly sensitive method to detect cancer biomarkers using silica encapsulated phase change nanoparticles as thermal barcodes. During phase changes, nanoparticles absorb heat energy without much temperature rise and show sharp melting peaks (0.6 °C). A series of phase change nanoparticles of metals or alloys can be synthesized in such a way that they melt between 100 and 700 °C, thus the multiplicity could reach 1000. The method has high sensitivity (8 nM) that can be enhanced using materials with large latent heat, nanoparticles with large diameter, or reducing the grafting density of biomolecules on nanoparticles.

Force generation and temperature-jump and length-jump tension transients in muscle fibers.

PubMed Central

Davis, J S; Rodgers, M E

1995-01-01

Muscle tension rises with increasing temperature. The kinetics that govern the tension rise of maximally Ca(2+)-activated, skinned rabbit psoas fibers over a temperature range of 0-30 degrees C was characterized in laser temperature-jump experiments. The kinetic response is simple and can be readily interpreted in terms of a basic three-step mechanism of contraction, which includes a temperature-sensitive rapid preequilibrium(a) linked to a temperature-insensitive rate-limiting step and followed by a temperature-sensitive tension-generating step. These data and mechanism are compared and contrasted with the more complex length-jump Huxley-Simmons phases in which all states that generate tension or bear tension are perturbed. The rate of the Huxley-Simmons phase 4 is temperature sensitive at low temperatures but plateaus at high temperatures, indicating a change in rate-limiting step from a temperature-sensitive (phase 4a) to a temperature-insensitive reaction (phase 4b); the latter appears to correlate with the slow, temperature-insensitive temperature-jump relaxation. Phase 3 is absent in the temperature-jump, which excludes it from tension generation. We confirm that de novo tension generation occurs as an order-disorder transition during phase 2slow and the equivalent, temperature-sensitive temperature-jump relaxation. PMID:7612845

Comparison of pelvic phased-array versus endorectal coil magnetic resonance imaging at 3 Tesla for local staging of prostate cancer.

PubMed

Kim, Bum Soo; Kim, Tae-Hwan; Kwon, Tae Gyun; Yoo, Eun Sang

2012-05-01

Several studies have demonstrated the superiority of endorectal coil magnetic resonance imaging (MRI) over pelvic phased-array coil MRI at 1.5 Tesla for local staging of prostate cancer. However, few have studied which evaluation is more accurate at 3 Tesla MRI. In this study, we compared the accuracy of local staging of prostate cancer using pelvic phased-array coil or endorectal coil MRI at 3 Tesla. Between January 2005 and May 2010, 151 patients underwent radical prostatectomy. All patients were evaluated with either pelvic phased-array coil or endorectal coil prostate MRI prior to surgery (63 endorectal coils and 88 pelvic phased-array coils). Tumor stage based on MRI was compared with pathologic stage. We calculated the specificity, sensitivity and accuracy of each group in the evaluation of extracapsular extension and seminal vesicle invasion. Both endorectal coil and pelvic phased-array coil MRI achieved high specificity, low sensitivity and moderate accuracy for the detection of extracapsular extension and seminal vesicle invasion. There were statistically no differences in specificity, sensitivity and accuracy between the two groups. Overall staging accuracy, sensitivity and specificity were not significantly different between endorectal coil and pelvic phased-array coil MRI.

Optical implementation of spin squeezing

NASA Astrophysics Data System (ADS)

Ono, Takafumi; Sabines-Chesterking, Javier; Cable, Hugo; O'Brien, Jeremy L.; Matthews, Jonathan C. F.

2017-05-01

Quantum metrology enables estimation of optical phase shifts with precision beyond the shot-noise limit. One way to exceed this limit is to use squeezed states, where the quantum noise of one observable is reduced at the expense of increased quantum noise for its complementary partner. Because shot-noise limits the phase sensitivity of all classical states, reduced noise in the average value for the observable being measured allows for improved phase sensitivity. However, additional phase sensitivity can be achieved using phase estimation strategies that account for the full distribution of measurement outcomes. Here we experimentally investigate a model of optical spin-squeezing, which uses post-selection and photon subtraction from the state generated using a parametric downconversion photon source, and we investigate the phase sensitivity of this model. The Fisher information for all photon-number outcomes shows it is possible to obtain a quantum advantage of 1.58 compared to the shot-noise value for five-photon events, even though due to experimental imperfection, the average noise for the relevant spin-observable does not achieve sub-shot-noise precision. Our demonstration implies improved performance of spin squeezing for applications to quantum metrology.

Spectral domain phase microscopy: a new tool for measuring cellular dynamics and cytoplasmic flow

NASA Astrophysics Data System (ADS)

McDowell, Emily J.; Choma, Michael A.; Ellerbee, Audrey K.; Izatt, Joseph A.

2005-03-01

Broadband interferometry is an attractive technique for the detection of cellular motions because it provides depth-resolved interferometric phase information via coherence gating. Here a phase sensitive technique called spectral domain phase microscopy (SDPM) is presented. SDPM is a functional extension of spectral domain optical coherence tomography that allows for the detection of cellular motions and dynamics with nanometer-scale sensitivity. This sensitivity is made possible by the inherent phase stability of spectral domain OCT combined with common-path interferometry. The theory that underlies this technique is presented, the sensitivity of the technique is demonstrated by the measurement of the thermal expansion coefficient of borosilicate glass, and the response of an Amoeba proteus to puncture of its cell membrane is measured. We also exploit the phase stability of SDPM to perform Doppler flow imaging of cytoplasmic streaming in A. proteus. We show reversal of cytoplasmic flow in response to stimuli, and we show that the cytoplasmic flow is laminar (i.e. parabolic) in nature. We are currently investigating the use of SDPM in a variety of different cell types.

[Phase transfer catalyzed bioconversion of penicillin G to 6-APA by immobilized penicillin acylase in recyclable aqueous two-phase systems with light/pH sensitive copolymers].

PubMed

Jin, Ke-ming; Cao, Xue-jun; Su, Jin; Ma, Li; Zhuang, Ying-ping; Chu, Ju; Zhang, Si-liang

2008-03-01

Immobilized penicillin acylase was used for bioconversion of penicillin PG into 6-APA in aqueous two-phase systems consisting of a light-sensitive polymer PNBC and a pH-sensitive polymer PADB. Partition coefficients of 6-APA was found to be about 5.78 in the presence of 1% NaCl. Enzyme kinetics showed that the reaction reached equilibrium at roughly 7 h. The 6-APA mole yields were 85.3% (pH 7.8, 20 degrees C), with about 20% increment as compared with the reaction of single aqueous phase buffer. The partition coefficient of PG (Na) varied scarcely, while that of the product, 6-APA and phenylacetic acid (PA) significantly varied due to Donnan effect of the phase systems and hydrophobicity of the products. The variation of the partition coefficients of the products also affected the bioconversion yield of the products. In the aqueous two-phase systems, the substrate, PG, the products of 6-APA and PA were biased in the top phase, while immobilized penicillin acylase at completely partitioned at the bottom. The substrate and PG entered the bottom phase, where it was catalyzed into 6-APA and PA and entered the top phase. Inhibition of the substrate and products was removed to result in improvement of the product yield, and the immobilized enzyme showed higher efficiency than the immobilized cells and occupied smaller volume. Compared with the free enzyme, immobilized enzyme had greater stability, longer life-time, and was completely partitioned in the bottom phase and recycle. Bioconversion in two-phase systems using immobilized penicillin acylase showed outstanding advantage. The light-sensitive copolymer forming aqueous two-phase systems could be recovered by laser radiation at 488 nm or filtered 450 nm light, while pH-sensitive polymer PADB could be recovered at the isoelectric point (pH 4.1). The recovery of the two copolymers was between 95% and 99%.

Paleoclimatological context and reference level of the 2°C and 1.5°C Paris Agreement long-term temperature limits

NASA Astrophysics Data System (ADS)

Lüning, Sebastian; Vahrenholt, Fritz

2017-12-01

The Paris Agreement adopted in December 2015 during the COP21 conference stipulates that the increase in the global average temperature is to be kept well below 2°C above “pre-industrial levels” and that efforts are pursued to limit the temperature increase to 1.5°C above “pre-industrial levels”. In order to further increase public acceptance of these limits it is important to transparently place the target levels and their baselines in a paleoclimatic context of the past 150,000 years (Last Interglacial, LIG) and in particular of the last 10,000 years (Holocene; Present Interglacial, PIG). Intense paleoclimatological research of the past decade has firmed up that pre-industrial temperatures have been highly variable which needs to be reflected in the pre-industrial climate baseline definitions. The currently used reference level 1850-1900 represents the end of the Little Ice Age (LIA).The LIA represents the coldest phase of the last 10,000 years when mean temperatures deviated strongly negatively from the Holocene average and which therefore are hard to justify as a representative pre-industrial baseline. The temperature level reached during the interval 1940-1970 may serve as a better reference level as it appears to roughly correspond to the average pre-industrial temperature of the past two millennia. Placing the climate limits in an enlarged paleoclimatic context will help to demonstrate that the chosen climate targets are valid and represent dangerous extremes of the known natural range of Holocene temperature variability.

Role of dorsal hippocampal orexin-1 receptors in memory restoration induced by morphine sensitization phenomenon.

PubMed

Alijanpour, S; Tirgar, F; Zarrindast, M-R

2016-01-15

The present study was examined the blockade of CA1 orexin-1 receptors (OX1Rs) of the dorsal hippocampus in the induction or expression phase on morphine sensitization-induced memory restoration using the Morris water maze (MWM) apparatus. Results showed that pre-training administration of morphine (5mg/kg, s.c.) increases escape latency and traveled distance, while does not alter swimming speed. This supports the impairing effect of morphine on the spatial memory acquisition in male adult rats. Also, in the retrieval session (probe trial) this treatment decreased the time spent in the target quadrant. Moreover, morphine-induced sensitization (15 or 20mg/kg, s.c.; once daily for 3days and followed by 5days no drug treatment) restored the memory acquisition/retrieval deficit which had been induced by pre-training administration of morphine (5mg/kg, s.c.). Intra-CA1 microinjection of subthreshold doses of SB-334867 (OX1Rs antagonist; 10, 20 and 40nmol/rat), 5min before morphine (20mg/kg/day×3days, s.c.; induction phase for morphine sensitization) did not alter restoration of memory acquisition/retrieval produced by the morphine sensitization phenomenon. In contrast, microinjection of subthreshold doses of SB-334867 (10, 20 and 40nmol/rat) into the CA1 region in the training session, 5min prior to morphine (5mg/kg, s.c.; expression phase for morphine sensitization) blocked the spatial memory acquisition/retrieval in morphine-sensitized rats. In conclusion, these findings show that morphine sensitization reverses morphine-induced amnesia. Furthermore, the blockade of CA1 OX1Rs in the expression phase, but not in the induction phase, disrupts memory restoration induced by morphine sensitization. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

The Effect of Heat Treatment on the Sensitized Corrosion of the 5383-H116 Al-Mg Alloy

PubMed Central

Lin, Ying-Kai; Wang, Shing-Hai; Chen, Ren-Yu; Hsieh, Tso-Sheng; Tsai, Liren; Chiang, Chia-Chin

2017-01-01

In this study, the effects of heat treatment and sensitized corrosion on the 5383-H116 Al-Mg alloy were investigated for temperatures ranging from 100 to 450 °C. The results show that the heat treatment temperature is the main factor that causes changes to the microstructure and mechanical strength of the 5383-H116 Al-Mg alloy, inducing β-phase (Al3Mg2) precipitation in the form of a continuous layer along the grain boundaries. Intergranular corrosion was caused by the β-phase of the grain boundary precipitation, and the corrosion susceptibility of the recrystallized structure was significantly higher than the corrosion susceptibility of the recovered structure. According to the conductivity values detected, β-phase precipitation can enhance the 5383-H116 Al-Mg alloy conductivity, with the response due to structural dislocation density being higher than that due to the recrystallized structure. As such, the β-phase precipitation after sensitization is more significant than the β-phase precipitation prior to the sensitization, such that after sensitization, the conductivity rises to a significantly higher level than that exhibited by the recrystallization structure. PMID:28772635

Frequency non-degenerate phase-sensitive optical parametric amplification based on four-wave-mixing in width-modulated silicon waveguides.

PubMed

Wang, Zhaolu; Liu, Hongjun; Sun, Qibing; Huang, Nan; Li, Xuefeng

2014-12-15

A width-modulated silicon waveguide is proposed to realize non-degenerate phase sensitive optical parametric amplification. It is found that the relative phase at the input of the phase sensitive amplifier (PSA) θIn-PSA can be tuned by tailoring the width and length of the second segment of the width-modulated silicon waveguide, which will influence the gain in the parametric amplification process. The maximum gain of PSA is larger by 9 dB compared with the phase insensitive amplifier (PIA) gain, and the gain bandwidth of PSA is larger by 35 nm compared with the gain bandwidth of PIA. Our on-chip PSA can find important potential applications in highly integrated optical circuits for optical chip-to-chip communication and computers.

Shot noise-limited Cramér-Rao bound and algorithmic sensitivity for wavelength shifting interferometry

NASA Astrophysics Data System (ADS)

Chen, Shichao; Zhu, Yizheng

2017-02-01

Sensitivity is a critical index to measure the temporal fluctuation of the retrieved optical pathlength in quantitative phase imaging system. However, an accurate and comprehensive analysis for sensitivity evaluation is still lacking in current literature. In particular, previous theoretical studies for fundamental sensitivity based on Gaussian noise models are not applicable to modern cameras and detectors, which are dominated by shot noise. In this paper, we derive two shot noiselimited theoretical sensitivities, Cramér-Rao bound and algorithmic sensitivity for wavelength shifting interferometry, which is a major category of on-axis interferometry techniques in quantitative phase imaging. Based on the derivations, we show that the shot noise-limited model permits accurate estimation of theoretical sensitivities directly from measured data. These results can provide important insights into fundamental constraints in system performance and can be used to guide system design and optimization. The same concepts can be generalized to other quantitative phase imaging techniques as well.

Sensitive determination of nitrophenol isomers by reverse-phase high-performance liquid chromatography in conjunction with liquid-liquid extraction

USDA-ARS?s Scientific Manuscript database

A method for the highly sensitive determination of 2-, 3- and 4- nitrophenols was developed using reverse-phase high-performance liquid chromatography (RP-HPLC) with a UV photodiode array detector. Using a reverse-phase column and 40% aqueous acetonitrile as an eluent (i.e. isocratic elution), the i...

Determination of complex formation constants by phase sensitive alternating current polarography: Cadmium-polymethacrylic acid and cadmium-polygalacturonic acid.

PubMed

Garrigosa, Anna Maria; Gusmão, Rui; Ariño, Cristina; Díaz-Cruz, José Manuel; Esteban, Miquel

2007-10-15

The use of phase sensitive alternating current polarography (ACP) for the evaluation of complex formation constants of systems where electrodic adsorption is present has been proposed. The applicability of the technique implies the previous selection of the phase angle where contribution of capacitive current is minimized. This is made using Multivariate Curve Resolution by Alternating Least Squares (MCR-ALS) in the analysis of ACP measurements at different phase angles. The method is checked by the study of the complexation of Cd by polymethacrylic (PMA) and polygalacturonic (PGA) acids, and the optimal phase angles have been ca. -10 degrees for Cd-PMA and ca. -15 degrees for Cd-PGA systems. The goodness of phase sensitive ACP has been demonstrated comparing the determined complex formation constants with those obtained by reverse pulse polarography, a technique that minimizes the electrode adsorption effects on the measured currents.

Approximated transport-of-intensity equation for coded-aperture x-ray phase-contrast imaging.

PubMed

Das, Mini; Liang, Zhihua

2014-09-15

Transport-of-intensity equations (TIEs) allow better understanding of image formation and assist in simplifying the "phase problem" associated with phase-sensitive x-ray measurements. In this Letter, we present for the first time to our knowledge a simplified form of TIE that models x-ray differential phase-contrast (DPC) imaging with coded-aperture (CA) geometry. The validity of our approximation is demonstrated through comparison with an exact TIE in numerical simulations. The relative contributions of absorption, phase, and differential phase to the acquired phase-sensitive intensity images are made readily apparent with the approximate TIE, which may prove useful for solving the inverse phase-retrieval problem associated with these CA geometry based DPC.

A primary method for the complex calibration of a hydrophone from 1 Hz to 2 kHz

NASA Astrophysics Data System (ADS)

Slater, W. H.; E Crocker, S.; Baker, S. R.

2018-02-01

A primary calibration method is demonstrated to obtain the magnitude and phase of the complex sensitivity for a hydrophone at frequencies between 1 Hz and 2 kHz. The measurement is performed in a coupler reciprocity chamber (‘coupler’) a closed test chamber where time harmonic oscillations in pressure can be achieved and the reciprocity conditions required for a primary calibration can be realized. Relevant theory is reviewed and the reciprocity parameter updated for the complex measurement. Systematic errors and corrections for magnitude are reviewed and more added for phase. The combined expanded uncertainties of the magnitude and phase of the complex sensitivity at 1 Hz were 0.1 dB re 1 V μ Pa-1 and  ± 1\\circ , respectively. Complex sensitivity, sensitivity magnitude, and phase measurements are presented on an example primary reference hydrophone.

Vibration-immune high-sensitivity profilometer built with the technique of composite interferometry.

PubMed

Lin, Yu-Kai; Chang, Chun-Wei; Hou, Max T; Hsu, I-Jen

2016-03-10

A prototype of a profilometer was built with the technique of composite interferometry for measurement of the distribution of both the amplitude and phase information of the surface of a material simultaneously. The composite interferometer was composed of a Michelson interferometer for measuring the surface profile of the sample and a Mach-Zehnder interferometer for measuring the phase deviation caused by the scanning component and environmental perturbations. A high-sensitivity surface profile can be obtained by use of the phase compensation mechanism through subtraction of the phases of the interferograms detected in the two interferometers. With the new design and improvement of robustness of the optical system, the measurement speed and accuracy were significantly improved. Furthermore, an additional optical delay component results in a higher sensitivity of the interference signal. This prototype of vibration-immune profilometer was examined to have a displacement sensitivity of 0.64 nm.

Raman-noise-induced quantum limits for χ(3) nondegenerate phase-sensitive amplification and quadrature squeezing

NASA Astrophysics Data System (ADS)

Voss, Paul L.; Köprülü, Kahraman G.; Kumar, Prem

2006-04-01

We present a quantum theory of nondegenerate phase-sensitive parametric amplification in a χ(3) nonlinear medium. The nonzero response time of the Kerr (χ(3)) nonlinearity determines the quantum-limited noise figure of χ(3) parametric amplification, as well as the limit on quadrature squeezing. This nonzero response time of the nonlinearity requires coupling of the parametric process to a molecular vibration phonon bath, causing the addition of excess noise through spontaneous Raman scattering. We present analytical expressions for the quantum-limited noise figure of frequency nondegenerate and frequency degenerate χ(3) parametric amplifiers operated as phase-sensitive amplifiers. We also present results for frequency nondegenerate quadrature squeezing. We show that our nondegenerate squeezing theory agrees with the degenerate squeezing theory of Boivin and Shapiro as degeneracy is approached. We have also included the effect of linear loss on the phase-sensitive process.

Phase-Sensitive Coherence and the Classical-Quantum Boundary in Ghost Imaging

NASA Technical Reports Server (NTRS)

Erkmen, Baris I.; Hardy, Nicholas D.; Venkatraman, Dheera; Wong, Franco N. C.; Shapiro, Jeffrey H.

2011-01-01

The theory of partial coherence has a long and storied history in classical statistical optics. the vast majority of this work addresses fields that are statistically stationary in time, hence their complex envelopes only have phase-insensitive correlations. The quantum optics of squeezed-state generation, however, depends on nonlinear interactions producing baseband field operators with phase-insensitive and phase-sensitive correlations. Utilizing quantum light to enhance imaging has been a topic of considerable current interest, much of it involving biphotons, i.e., streams of entangled-photon pairs. Biphotons have been employed for quantum versions of optical coherence tomography, ghost imaging, holography, and lithography. However, their seemingly quantum features have been mimicked with classical-sate light, questioning wherein lies the classical-quantum boundary. We have shown, for the case of Gaussian-state light, that this boundary is intimately connected to the theory of phase-sensitive partial coherence. Here we present that theory, contrasting it with the familiar case of phase-insensitive partial coherence, and use it to elucidate the classical-quantum boundary of ghost imaging. We show, both theoretically and experimentally, that classical phase-sensitive light produces ghost imaging most closely mimicking those obtained in biphotons, and we derived the spatial resolution, image contrast, and signal-to-noise ratio of a standoff-sensing ghost imager, taking into account target-induced speckle.

Comparison of Pelvic Phased-Array versus Endorectal Coil Magnetic Resonance Imaging at 3 Tesla for Local Staging of Prostate Cancer

PubMed Central

Kim, Bum Soo; Kim, Tae-Hwan; Kwon, Tae Gyun

2012-01-01

Purpose Several studies have demonstrated the superiority of endorectal coil magnetic resonance imaging (MRI) over pelvic phased-array coil MRI at 1.5 Tesla for local staging of prostate cancer. However, few have studied which evaluation is more accurate at 3 Tesla MRI. In this study, we compared the accuracy of local staging of prostate cancer using pelvic phased-array coil or endorectal coil MRI at 3 Tesla. Materials and Methods Between January 2005 and May 2010, 151 patients underwent radical prostatectomy. All patients were evaluated with either pelvic phased-array coil or endorectal coil prostate MRI prior to surgery (63 endorectal coils and 88 pelvic phased-array coils). Tumor stage based on MRI was compared with pathologic stage. We calculated the specificity, sensitivity and accuracy of each group in the evaluation of extracapsular extension and seminal vesicle invasion. Results Both endorectal coil and pelvic phased-array coil MRI achieved high specificity, low sensitivity and moderate accuracy for the detection of extracapsular extension and seminal vesicle invasion. There were statistically no differences in specificity, sensitivity and accuracy between the two groups. Conclusion Overall staging accuracy, sensitivity and specificity were not significantly different between endorectal coil and pelvic phased-array coil MRI. PMID:22476999

Phases transitions and interfaces in temperature-sensitive colloidal systems

NASA Astrophysics Data System (ADS)

Nguyen, Duc; Schall, Peter

2013-03-01

Colloids are widely used because of their exceptional properties. Beside their own applications in food, petrol, cosmetics and drug industries, photonic, optical filters and chemical sensor, they are also known as powerful model systems to study molecular phase behavior. Here, we examine both aspects of colloids using temperature-sensitive colloidal systems to fully investigate colloidal phase behavior and colloidal assembly.

High-speed spectral calibration by complex FIR filter in phase-sensitive optical coherence tomography.

PubMed

Kim, Sangmin; Raphael, Patrick D; Oghalai, John S; Applegate, Brian E

2016-04-01

Swept-laser sources offer a number of advantages for Phase-sensitive Optical Coherence Tomography (PhOCT). However, inter- and intra-sweep variability leads to calibration errors that adversely affect phase sensitivity. While there are several approaches to overcoming this problem, our preferred method is to simply calibrate every sweep of the laser. This approach offers high accuracy and phase stability at the expense of a substantial processing burden. In this approach, the Hilbert phase of the interferogram from a reference interferometer provides the instantaneous wavenumber of the laser, but is computationally expensive. Fortunately, the Hilbert transform may be approximated by a Finite Impulse-Response (FIR) filter. Here we explore the use of several FIR filter based Hilbert transforms for calibration, explicitly considering the impact of filter choice on phase sensitivity and OCT image quality. Our results indicate that the complex FIR filter approach is the most robust and accurate among those considered. It provides similar image quality and slightly better phase sensitivity than the traditional FFT-IFFT based Hilbert transform while consuming fewer resources in an FPGA implementation. We also explored utilizing the Hilbert magnitude of the reference interferogram to calculate an ideal window function for spectral amplitude calibration. The ideal window function is designed to carefully control sidelobes on the axial point spread function. We found that after a simple chromatic correction, calculating the window function using the complex FIR filter and the reference interferometer gave similar results to window functions calculated using a mirror sample and the FFT-IFFT Hilbert transform. Hence, the complex FIR filter can enable accurate and high-speed calibration of the magnitude and phase of spectral interferograms.

High-speed spectral calibration by complex FIR filter in phase-sensitive optical coherence tomography

PubMed Central

Kim, Sangmin; Raphael, Patrick D.; Oghalai, John S.; Applegate, Brian E.

2016-01-01

Swept-laser sources offer a number of advantages for Phase-sensitive Optical Coherence Tomography (PhOCT). However, inter- and intra-sweep variability leads to calibration errors that adversely affect phase sensitivity. While there are several approaches to overcoming this problem, our preferred method is to simply calibrate every sweep of the laser. This approach offers high accuracy and phase stability at the expense of a substantial processing burden. In this approach, the Hilbert phase of the interferogram from a reference interferometer provides the instantaneous wavenumber of the laser, but is computationally expensive. Fortunately, the Hilbert transform may be approximated by a Finite Impulse-Response (FIR) filter. Here we explore the use of several FIR filter based Hilbert transforms for calibration, explicitly considering the impact of filter choice on phase sensitivity and OCT image quality. Our results indicate that the complex FIR filter approach is the most robust and accurate among those considered. It provides similar image quality and slightly better phase sensitivity than the traditional FFT-IFFT based Hilbert transform while consuming fewer resources in an FPGA implementation. We also explored utilizing the Hilbert magnitude of the reference interferogram to calculate an ideal window function for spectral amplitude calibration. The ideal window function is designed to carefully control sidelobes on the axial point spread function. We found that after a simple chromatic correction, calculating the window function using the complex FIR filter and the reference interferometer gave similar results to window functions calculated using a mirror sample and the FFT-IFFT Hilbert transform. Hence, the complex FIR filter can enable accurate and high-speed calibration of the magnitude and phase of spectral interferograms. PMID:27446666

Phase-sensitive terahertz spectroscopy with backward-wave oscillators in reflection mode.

PubMed

Pronin, A V; Goncharov, Yu G; Fischer, T; Wosnitza, J

2009-12-01

In this article we describe a method which allows accurate measurements of the complex reflection coefficient r = absolute value(r) x exp(i phi(R)) of a solid at frequencies of 1-50 cm(-1) (30 GHz-1.5 THz). Backward-wave oscillators are used as sources for monochromatic coherent radiation tunable in frequency. The amplitude of the complex reflection (the reflectivity) is measured in a standard way, while the phase shift, introduced by the reflection from the sample surface, is measured using a Michelson interferometer. This method is particular useful for nontransparent samples, where phase-sensitive transmission measurements are not possible. The method requires no Kramers-Kronig transformation in order to extract the sample's electrodynamic properties (such as the complex dielectric function or complex conductivity). Another area of application of this method is the study of magnetic materials with complex dynamic permeabilities different from unity at the measurement frequencies (for example, colossal-magnetoresistance materials and metamaterials). Measuring both the phase-sensitive transmission and the phase-sensitive reflection allows for a straightforward model-independent determination of the dielectric permittivity and magnetic permeability of such materials.

Phase-sensitive terahertz spectroscopy with backward-wave oscillators in reflection mode

NASA Astrophysics Data System (ADS)

Pronin, A. V.; Goncharov, Yu. G.; Fischer, T.; Wosnitza, J.

2009-12-01

In this article we describe a method which allows accurate measurements of the complex reflection coefficient r̂=|r̂|ṡexp(iφR) of a solid at frequencies of 1-50 cm-1 (30 GHz-1.5 THz). Backward-wave oscillators are used as sources for monochromatic coherent radiation tunable in frequency. The amplitude of the complex reflection (the reflectivity) is measured in a standard way, while the phase shift, introduced by the reflection from the sample surface, is measured using a Michelson interferometer. This method is particular useful for nontransparent samples, where phase-sensitive transmission measurements are not possible. The method requires no Kramers-Kronig transformation in order to extract the sample's electrodynamic properties (such as the complex dielectric function or complex conductivity). Another area of application of this method is the study of magnetic materials with complex dynamic permeabilities different from unity at the measurement frequencies (for example, colossal-magnetoresistance materials and metamaterials). Measuring both the phase-sensitive transmission and the phase-sensitive reflection allows for a straightforward model-independent determination of the dielectric permittivity and magnetic permeability of such materials.

Improved phase sensitivity in spectral domain phase microscopy using line-field illumination and self phase-referencing

PubMed Central

Yaqoob, Zahid; Choi, Wonshik; Oh, Seungeun; Lue, Niyom; Park, Yongkeun; Fang-Yen, Christopher; Dasari, Ramachandra R.; Badizadegan, Kamran; Feld, Michael S.

2010-01-01

We report a quantitative phase microscope based on spectral domain optical coherence tomography and line-field illumination. The line illumination allows self phase-referencing method to reject common-mode phase noise. The quantitative phase microscope also features a separate reference arm, permitting the use of high numerical aperture (NA > 1) microscope objectives for high resolution phase measurement at multiple points along the line of illumination. We demonstrate that the path-length sensitivity of the instrument can be as good as 41 pm/Hz, which makes it suitable for nanometer scale study of cell motility. We present the detection of natural motions of cell surface and two-dimensional surface profiling of a HeLa cell. PMID:19550464

Sensitivity analysis and optimization method for the fabrication of one-dimensional beam-splitting phase gratings

PubMed Central

Pacheco, Shaun; Brand, Jonathan F.; Zaverton, Melissa; Milster, Tom; Liang, Rongguang

2015-01-01

A method to design one-dimensional beam-spitting phase gratings with low sensitivity to fabrication errors is described. The method optimizes the phase function of a grating by minimizing the integrated variance of the energy of each output beam over a range of fabrication errors. Numerical results for three 1x9 beam splitting phase gratings are given. Two optimized gratings with low sensitivity to fabrication errors were compared with a grating designed for optimal efficiency. These three gratings were fabricated using gray-scale photolithography. The standard deviation of the 9 outgoing beam energies in the optimized gratings were 2.3 and 3.4 times lower than the optimal efficiency grating. PMID:25969268

Direct comparison of phase-sensitive vibrational sum frequency generation with maximum entropy method: case study of water.

PubMed

de Beer, Alex G F; Samson, Jean-Sebastièn; Hua, Wei; Huang, Zishuai; Chen, Xiangke; Allen, Heather C; Roke, Sylvie

2011-12-14

We present a direct comparison of phase sensitive sum-frequency generation experiments with phase reconstruction obtained by the maximum entropy method. We show that both methods lead to the same complex spectrum. Furthermore, we discuss the strengths and weaknesses of each of these methods, analyzing possible sources of experimental and analytical errors. A simulation program for maximum entropy phase reconstruction is available at: http://lbp.epfl.ch/. © 2011 American Institute of Physics

Phase-sensitive fiber-based parametric all-optical switch.

PubMed

Parra-Cetina, Josué; Kumpera, Aleš; Karlsson, Magnus; Andrekson, Peter A

2015-12-28

We experimentally demonstrate, for the first time, an all-optical switch in a phase-sensitive fiber optic parametric amplifier operated in saturation. We study the effect of phase variation of the signal and idler waves on the pump power depletion. By changing the phase of a 0.9 mW signal/idler pair wave by π/2 rad, a pump power extinction ratio of 30.4 dB is achieved. Static and dynamic characterizations are also performed and time domain results presented.

Sensitivity of a Wave Structure to Initial Conditions

NASA Technical Reports Server (NTRS)

Duval, Walter M. B.; Duval, Walter M. B. (Technical Monitor)

2000-01-01

Microgravity experiments aimed at quantifying effects of gentler via controlled sinusoidal forcing transmitted on the interface between two miscible liquids have shown the evolution of a quasi -stationary four-mode wave structure oriented vertically. The sensitivity of the wave structure to phase angle variation is investigated computationally. We show that a slight variation of the phase angle is sufficient to cause a bifurcation to a two-mode structure. The dependence of phase angle on wave structure is attributed to sensitivity on initial conditions due to the strong nonlinearity of the coupled field equations for the parametric space of interest.

Evaluating climate controls on isotopic shifts in high-altitude forests during the Last Interglacial

NASA Astrophysics Data System (ADS)

Insel, N.; Berkelhammer, M. B.; Sturm, C.; Karimova, G.

2016-12-01

Forests play a significant role in the global carbon cycle, and influence climate through their effect on albedo and latent heat flux. Predicting the response of these ecosystems to climate change is complicated by competing influences between rising CO2, warming, and shifts in hydrology such as timing, rate, and type of precipitation. A key to detection and prediction of future regional and global changes of modern ecosystems lies in understanding the causes and characteristics of historical variations at the ecosystem level. The Last Interglacial (LIG: 130 to 116 ka) is the most recent period in Earth's history when growing season temperature exceeded those of today. In this study, we are using isotope-enabled regional climate model (REMOiso) simulations under LIG (115ka, 125 ka and 135 ka) and modern forcings to evaluate climate controls on boreal forest in the western US. In particular, we investigate (1) changes in moisture sources and moisture transport, (2) changes in the annual and seasonal extent and duration of precipitation, and (3) temperature variations to explore how ecosystem carbon and water fluxes change under coupled temperature and precipitation variability. Eemian wood samples from the Rocky Mountains in Colorado show a progressive increase in the 18O seasonal cycle that may be related to trees utilizing isotopically enriched monsoonal moisture. However, Eemian climate simulations (125ka) incorporate orbital forcings that result in stronger seasonal changes in temperature, precipitation, and snow cover in comparison to today, while annual anomalies are small. The seasonal shift in climate affects the water availability and the length of growing season for Eemian plants. Model results indicate only a very slight increase in monsoonal moisture transport from the south, resulting in slightly wetter conditions in western Colorado, but slightly drier conditions in the eastern part. Preliminary results suggest that changes in the North American monsoon system were not sufficient to explain the observed isotopic enrichment in Eemian wood samples. Current isotope simulations address changes in the seasonal isotopic cycle in the precipitation during the Eemian and will allow us to distinguish tree's reliance on summer or winter moisture sources more clearly.

Ion Exchange Studies for Removal of Sulfate from Hanford Tank Waste Envelope C (241-AN-107) Using SuperLig 655 Resin

DOE Office of Scientific and Technical Information (OSTI.GOV)

DE Kurath; JR Bontha; DL Blanchard

BNFL Inc. is evaluating various pretreatment technologies to mitigate the impacts of sulfate on the LAW vitrification system. One pretreatment technology for separating sulfate from LAW solutions involves the use of SuperLig{reg_sign} 655 (SL-655), a proprietary ion exchange material developed and supplied by IBC Advanced Technologies, Inc., American Fork, UT. This report describes testing of SL-655 with diluted ([Na] {approximately} 5 M) waste from Hanford Tank 241-AN-107 at Battelle, Pacific Northwest Division. Batch contact studies were conducted from 4 to 96 hours to determine the sulfate distribution coefficient and reaction kinetics. A small-scale ion exchange column test was conducted tomore » evaluate sulfate removal, loading, breakthrough, and elution from the SL-655. In all of these tests, an archived 241-AN-107 tank waste sample (pretreated to remove Cs, Sr, and transuranics elements) was used. The experimental details and results are described in this report. Under the test conditions, SL-655 was found to have no significant ion exchange affinity for sulfate in this matrix. The batch contact study resulted in no measurable difference in the aqueous sulfate concentration following resin contact (K{sub d} {approximately} 0). The column test also demonstrated SL-655 had no practical affinity for sulfate in the tested matrix. Within experimental error, the sulfate concentration in the column effluent was equal to the concentration in the feed after passing 3 bed volumes of sample through the columns. Furthermore, some, if not all, of the decreased sulfate concentration in these first three column volumes of effluent can be ascribed to mixing and dilution of the 241-AN-107 feed with the interstitial liquid present in the column at the start of the loading cycle. Finally, ICP-AES measurements on the eluate solutions showed the presence of barium as soon as contact with the feed solution is completed. Barium is a metal not detected in the feed solution. Should the loss of barium be correlated with the resin's ability to selectively complex sulfate, then maintaining even the current limited resin characteristics for sulfate complexation over multiple cycles becomes questionable.« less

Evolution of a Greenland Ice sheet Including Shelves and Regional Sea Level Variations

NASA Astrophysics Data System (ADS)

Bradley, S.; Reerink, T.; Vandewal, R.; Helsen, M.

2015-12-01

Observational evidence, including offshore moraines and marine sediment cores infer that at the Last Glacial maximum (LGM) the Greenland ice sheet (GIS) grounded out across the Davis Strait into Baffin Bay, with fast flowing ice streams extending out to the continental shelf break along the NW margin. These observations lead to a number of questions as to weather the GIS and Laurentide ice sheet (LIS) coalesced during glacial maximums, and if so, did a significant ice shelf develop across Baffin Bay and how would such a configuration impact on the relative contribution of these ice sheets to eustatic sea level (ESL). Most previous paleo ice sheet modelling simulations of the GIS recreated an ice sheet that either did not extend out onto the continental shelf or utilised a simplified marine ice parameterisation to recreate an extended GIS, and therefore did not fully include ice shelf dynamics. In this study we simulate the evolution of the GIS from 220 kyr BP to present day using IMAU-ice; a 3D thermodynamical ice sheet model which fully accounts for grounded and floating ice, calculates grounding line migration and ice shelf dynamics. There is few observational estimates of long-term (yrs) sub marine basal melting rates (mbm) for the GIS. Therefore we investigate a range of relationships to constrain the spatial and temporal parameterisation of mbm within IMAU-ice related to changes in paleo water depth, driven by changes in relative sea level and ocean temperature. We will present results of how changes in the mbm directly impacts on the ice sheet dynamics, timing and spatial extent of the GIS at the glacial maximums, but also on the rate of retreat and spatial extent at the Last interglacial (LIG) minimum. Initial results indicate that with the inclusion of ice shelf dynamics, a larger GIS is generated which is grounded out into Davis strait, up to a water depth of -750 m, but the total contribution to LIG ESL is reduced by up to 0.6 m.

Quaternary onset and evolution of Kimberley coral reefs (Northwest Australia) revealed by high-resolution seismic imaging

NASA Astrophysics Data System (ADS)

Bufarale, Giada; Collins, Lindsay B.; O'Leary, Michael J.; Stevens, Alexandra; Kordi, Moataz; Solihuddin, Tubagus

2016-07-01

The inner shelf Kimberley Bioregion of Northwest Australia is characterised by a macrotidal setting where prolific coral reefs growth as developed around a complex drowned landscape and is considered a biodiversity "hotspot". High-resolution shallow seismic studies were conducted across various reef settings in the Kimberley (Buccaneer Archipelago, north of Dampier Peninsula, latitude: between 16°40‧S and 16°00‧S) to evaluate stratigraphic evolution, interaction with different substrates, morphological patterns and distribution. Reef sites were chosen to assess most of the reef types present, particularly high intertidal planar reefs and fringing reefs. Reef internal acoustic reflectors were identified according to their shape, stratigraphic position and characteristics. Two main seismic horizons were identified marking the boundaries between Holocene reef (Marine Isotope Stage 1, MIS 1, last 12 ky), commonly 10-20 m thick, and MIS 5 (Last Interglacial, LIG, ~120 ky, up to 12 m thick) and Proterozoic rock foundation over which Quaternary reef growth occurred. Within the Holocene Reef unit, at least three minor internal reflectors, generally discontinuous, subparallel to the reef flat were recognised and interpreted as either growth hiatuses or a change of the coral framework or sediment matrix. The LIG reefs represent a new northernmost occurrence along the Western Australian coast. The research presented here achieved the first regional geophysical study of the Kimberley reefs. Subbottom profiles demonstrated that the surveyed reefs are characterised by a multi-stage reef buildup, indicating that coral growth occurred in the Kimberley during previous sea level highstands. The data show also that antecedent substrate and regional subsidence have contributed, too, in determining the amount of accommodation available for reef growth and controlling the morphology of the successive reef building stages. Moreover, the study showed that in spite of macrotidal conditions, high-turbidity and frequent high-energy cyclonic events, corals have exhibited prolific reef growth during the Holocene developing significant reef accretionary structures. As a result coral reefs have generating habitat complexity and species diversity in what is a biodiversity hotspot.

Integrative inference of population history in the Ibero-Maghrebian endemic Pleurodeles waltl (Salamandridae).

PubMed

Gutiérrez-Rodríguez, Jorge; Barbosa, A Márcia; Martínez-Solano, Íñigo

2017-07-01

Inference of population histories from the molecular signatures of past demographic processes is challenging, but recent methodological advances in species distribution models and their integration in time-calibrated phylogeographic studies allow detailed reconstruction of complex biogeographic scenarios. We apply an integrative approach to infer the evolutionary history of the Iberian ribbed newt (Pleurodeles waltl), an Ibero-Maghrebian endemic with populations north and south of the Strait of Gibraltar. We analyzed an extensive multilocus dataset (mitochondrial and nuclear DNA sequences and ten polymorphic microsatellite loci) and found a deep east-west phylogeographic break in Iberian populations dating back to the Plio-Pleistocene. This break is inferred to result from vicariance associated with the formation of the Guadalquivir river basin. In contrast with previous studies, North African populations showed exclusive mtDNA haplotypes, and formed a monophyletic clade within the Eastern Iberian lineage in the mtDNA genealogy. On the other hand, microsatellites failed to recover Moroccan populations as a differentiated genetic cluster. This is interpreted to result from post-divergence gene flow based on the results of IMA2 and Migrate analyses. Thus, Moroccan populations would have originated after overseas dispersal from the Iberian Peninsula in the Pleistocene, with subsequent gene flow in more recent times, implying at least two trans-marine dispersal events. We modeled the distribution of the species and of each lineage, and projected these models back in time to infer climatically favourable areas during the mid-Holocene, the last glacial maximum (LGM) and the last interglacial (LIG), to reconstruct more recent population dynamics. We found minor differences in climatic favourability across lineages, suggesting intraspecific niche conservatism. Genetic diversity was significantly correlated with the intersection of environmental favourability in the LIG and LGM, indicating that populations of P. waltl are genetically more diverse in regions that have remained environmentally favourable through the last glacial cycle, particularly southern Iberia and northern Morocco. This study provides novel insights into the relative roles of geology and climate on the biogeography of a biodiversity hotspot. Copyright © 2017 Elsevier Inc. All rights reserved.

Sensitivity of a phase-sensitive optical time-domain reflectometer with a semiconductor laser source

NASA Astrophysics Data System (ADS)

Alekseev, A. E.; Tezadov, Ya A.; Potapov, V. T.

2018-06-01

In the present paper we perform, for the first time, an analysis of the average sensitivity of a coherent phase-sensitive optical time-domain reflectometer (phase-OTDR) with a semiconductor laser source to external actions. The sensitivity of this OTDR can be defined in a conventional manner via average SNR at its output, which in turn is defined by the average useful signal power and the average intensity noise power in the OTDR spatial channels in the bandwidth defined by the OTDR sampling frequency. The average intensity noise power is considered in detail in a previous paper. In the current paper we examine the average useful signal power at the output of a phase-OTDR. The analysis of the average useful signal power of a phase-OTDR is based on the study of a fiber scattered-light interferometer (FSLI) which is treated as a constituent part of a phase- OTDR. In the analysis, one of the conventional phase-OTDR schemes with a rectangular dual-pulse probe signal is considered. The FSLI which corresponds to this OTDR scheme has two scattering fiber segments with additional time delay, introduced between backscattered fields. The average useful signal power and the resulting average SNR at the output of this FSLI are determined by the degree of coherence of the semiconductor laser source, the length of the scattering fiber segments, and by the additional time delay between the scattering fiber segments. The average useful signal power characteristic of the corresponding phase-OTDR is determined by analogous parameters: the source coherence, the time durations of the parts constituting the dual-pulse, and the time interval which separates these parts. In the paper an expression for the average useful signal power of a phase-OTDR is theoretically derived and experimentally verified. Based on the found average useful signal power of a phase-OTDR and the average intensity noise power, derived in the previous paper, the average SNR of a phase-OTDR is defined. Setting the average signal SNR to 1, at a defined spectral band the minimum detectable external action amplitude for our particular phase-OTDR setup is determined. We also derive a simple relation for the average useful signal power and the average SNR which results when making the assumption that the laser source coherence is high. The results of the paper can serve as the basis for further development of the concept of phase-OTDR sensitivity.

Acute Normal Tissue Reactions in Head-and-Neck Cancer Patients Treated With IMRT: Influence of Dose and Association With Genetic Polymorphisms in DNA DSB Repair Genes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Werbrouck, Joke; Ruyck, Kim de; Duprez, Frederic

2009-03-15

Purpose: To investigate the association between dose-related parameters and polymorphisms in DNA DSB repair genes XRCC3 (c.-1843A>G, c.562-14A>G, c.722C>T), Rad51 (c.-3429G>C, c.-3392G>T), Lig4 (c.26C>T, c.1704T>C), Ku70 (c.-1310C>G), and Ku80 (c.2110-2408G>A) and the occurrence of acute reactions after radiotherapy. Materials and Methods: The study population consisted of 88 intensity-modulated radiation therapy (IMRT)-treated head-and-neck cancer patients. Mucositis, dermatitis, and dysphagia were scored using the Common Terminology Criteria (CTC) for Adverse Events v.3.0 scale. The population was divided into a CTC0-2 and CTC3+ group for the analysis of each acute effect. The influence of the dose on critical structures was analyzed using dose-volumemore » histograms. Genotypes were determined by polymerase chain reaction (PCR) combined with restriction fragment length polymorphism or PCR-single base extension assays. Results: The mean dose (D{sub mean}) to the oral cavity and constrictor pharyngeus (PC) muscles was significantly associated with the development of mucositis and dysphagia, respectively. These parameters were considered confounding factors in the radiogenomics analyses. The XRCC3c.722CT/TT and Ku70c.-1310CG/GG genotypes were significantly associated with the development of severe dysphagia (CTC3+). No association was found between the investigated polymorphisms and the development of mucositis or dermatitis. A risk analysis model for severe dysphagia, which was developed based on the XRCC3c.722CT/TT and Ku70c.-1310CG/GG genotypes and the PC dose, showed a sensitivity of 78.6% and a specificity of 77.6%. Conclusions: The XRCC3c.722C>T and Ku70c.-1310C>G polymorphisms as well as the D{sub mean} to the PC muscles were highly associated with the development of severe dysphagia after IMRT. The prediction model developed using these parameters showed a high sensitivity and specificity.« less

CO2 Push-Pull Dual (Conjugate) Faults Injection Simulations

DOE Data Explorer

Oldenburg, Curtis (ORCID:0000000201326016); Lee, Kyung Jae; Doughty, Christine; Jung, Yoojin; Borgia, Andrea; Pan, Lehua; Zhang, Rui; Daley, Thomas M.; Altundas, Bilgin; Chugunov, Nikita

2017-07-20

This submission contains datasets and a final manuscript associated with a project simulating carbon dioxide push-pull into a conjugate fault system modeled after Dixie Valley- sensitivity analysis of significant parameters and uncertainty prediction by data-worth analysis. Datasets include: (1) Forward simulation runs of standard cases (push & pull phases), (2) Local sensitivity analyses (push & pull phases), and (3) Data-worth analysis (push & pull phases).

Phase-sensitive X-ray imager

DOEpatents

Baker, Kevin Louis

2013-01-08

X-ray phase sensitive wave-front sensor techniques are detailed that are capable of measuring the entire two-dimensional x-ray electric field, both the amplitude and phase, with a single measurement. These Hartmann sensing and 2-D Shear interferometry wave-front sensors do not require a temporally coherent source and are therefore compatible with x-ray tubes and also with laser-produced or x-pinch x-ray sources.

Optical Fibers Would Sense Local Strains

NASA Technical Reports Server (NTRS)

Egalon, Claudio O.; Rogowski, Robert S.

1994-01-01

Proposed fiber-optic transducers measure local strains. Includes lead-in and lead-out lengths producing no changes in phase shifts, plus short sensing length in which phase shift is sensitive to strain. Phase shifts in single-mode fibers vary with strains. In alternative version, multiple portions of optical fiber sensitive to strains characteristic of specific vibrational mode of object. Same principle also used with two-mode fiber.

Coma measurement by use of an alternating phase-shifting mask mark with a specific phase width

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiu Zicheng; Wang Xiangzhao; Yuan Qiongyan

2009-01-10

The correlation between the coma sensitivity of the alternating phase-shifting mask (Alt-PSM) mark and the mark's structure is studied based on the Hopkins theory of partially coherent imaging and positive resist optical lithography (PROLITH) simulation. It is found that an optimized Alt-PSM mark with its phase width being two-thirds its pitch has a higher sensitivity to coma than Alt-PSM marks with the same pitch and the different phase widths. The pitch of the Alt-PSM mark is also optimized by PROLITH simulation, and the structure of p=1.92{lambda}/NA and pw=2p/3 proves to be with the highest sensitivity. The optimized Alt-PSM mark ismore » used as a measurement mark to retrieve coma aberration from the projection optics in lithographic tools. In comparison with an ordinary Alt-PSM mark with its phase width being a half its pitch, the measurement accuracies of Z7 and Z14 apparently increase.« less

Observational constraints on mixed-phase clouds imply higher climate sensitivity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tan, Ivy; Storelvmo, Trude; Zelinka, Mark D.

Global climate model (GCM) estimates of the equilibrium global mean surface temperature response to a doubling of atmospheric CO 2, measured by the equilibrium climate sensitivity (ECS), range from 2.0° to 4.6°C. Clouds are among the leading causes of this uncertainty. Here, in this paper, we show that the ECS can be up to 1.3°C higher in simulations where mixed-phase clouds consisting of ice crystals and supercooled liquid droplets are constrained by global satellite observations. The higher ECS estimates are directly linked to a weakened cloud-phase feedback arising from a decreased cloud glaciation rate in a warmer climate. Finally, wemore » point out the need for realistic representations of the supercooled liquid fraction in mixed-phase clouds in GCMs, given the sensitivity of the ECS to the cloud-phase feedback.« less

A Chain of Modeling Tools For Gas and Aqueous Phase Chemstry

NASA Astrophysics Data System (ADS)

Audiffren, N.; Djouad, R.; Sportisse, B.

Atmospheric chemistry is characterized by the use of large set of chemical species and reactions. Handling with the set of data required for the definition of the model is a quite difficult task. We prsent in this short article a preprocessor for diphasic models (gas phase and aqueous phase in cloud droplets) named SPACK. The main interest of SPACK is the automatic generation of lumped species related to fast equilibria. We also developped a linear tangent model using the automatic differentiation tool named ODYSSEE in order to perform a sensitivity analysis of an atmospheric multi- phase mechanism based on RADM2 kinetic scheme.Local sensitivity coefficients are computed for two different scenarii. We focus in this study on the sensitivity of the ozone,NOx,HOx, system with respect to some aqueous phase reactions and we inves- tigate the influence of the reduction in the photolysis rates in the area below the cloud region.

Observational constraints on mixed-phase clouds imply higher climate sensitivity

DOE PAGES

Tan, Ivy; Storelvmo, Trude; Zelinka, Mark D.

2016-04-08

Global climate model (GCM) estimates of the equilibrium global mean surface temperature response to a doubling of atmospheric CO 2, measured by the equilibrium climate sensitivity (ECS), range from 2.0° to 4.6°C. Clouds are among the leading causes of this uncertainty. Here, in this paper, we show that the ECS can be up to 1.3°C higher in simulations where mixed-phase clouds consisting of ice crystals and supercooled liquid droplets are constrained by global satellite observations. The higher ECS estimates are directly linked to a weakened cloud-phase feedback arising from a decreased cloud glaciation rate in a warmer climate. Finally, wemore » point out the need for realistic representations of the supercooled liquid fraction in mixed-phase clouds in GCMs, given the sensitivity of the ECS to the cloud-phase feedback.« less

Observational constraints on mixed-phase clouds imply higher climate sensitivity.

PubMed

Tan, Ivy; Storelvmo, Trude; Zelinka, Mark D

2016-04-08

Global climate model (GCM) estimates of the equilibrium global mean surface temperature response to a doubling of atmospheric CO2, measured by the equilibrium climate sensitivity (ECS), range from 2.0° to 4.6°C. Clouds are among the leading causes of this uncertainty. Here we show that the ECS can be up to 1.3°C higher in simulations where mixed-phase clouds consisting of ice crystals and supercooled liquid droplets are constrained by global satellite observations. The higher ECS estimates are directly linked to a weakened cloud-phase feedback arising from a decreased cloud glaciation rate in a warmer climate. We point out the need for realistic representations of the supercooled liquid fraction in mixed-phase clouds in GCMs, given the sensitivity of the ECS to the cloud-phase feedback. Copyright © 2016, American Association for the Advancement of Science.

Circadian phase, dynamics of subjective sleepiness and sensitivity to blue light in young adults complaining of a delayed sleep schedule.

PubMed

Moderie, Christophe; Van der Maren, Solenne; Dumont, Marie

2017-06-01

To assess factors that might contribute to a delayed sleep schedule in young adults with sub-clinical features of delayed sleep phase disorder. Two groups of 14 young adults (eight women) were compared: one group complaining of a delayed sleep schedule and a control group with an earlier bedtime and no complaint. For one week, each subject maintained a target bedtime reflecting their habitual sleep schedule. Subjects were then admitted to the laboratory for the assessment of circadian phase (dim light melatonin onset), subjective sleepiness, and non-visual light sensitivity. All measures were timed relative to each participant's target bedtime. Non-visual light sensitivity was evaluated using subjective sleepiness and salivary melatonin during 1.5-h exposure to blue light, starting one hour after target bedtime. Compared to control subjects, delayed subjects had a later circadian phase and a slower increase of subjective sleepiness in the late evening. There was no group difference in non-visual sensitivity to blue light, but we found a positive correlation between melatonin suppression and circadian phase within the delayed group. Our results suggest that a late circadian phase, a slow build-up of sleep need, and an increased circadian sensitivity to blue light contribute to the complaint of a delayed sleep schedule. These findings provide targets for strategies aiming to decreasing the severity of a sleep delay and the negative consequences on daytime functioning and health. Copyright © 2017 Elsevier B.V. All rights reserved.

Reconstruction-free sensitive wavefront sensor based on continuous position sensitive detectors.

PubMed

Godin, Thomas; Fromager, Michael; Cagniot, Emmanuel; Brunel, Marc; Aït-Ameur, Kamel

2013-12-01

We propose a new device that is able to perform highly sensitive wavefront measurements based on the use of continuous position sensitive detectors and without resorting to any reconstruction process. We demonstrate experimentally its ability to measure small wavefront distortions through the characterization of pump-induced refractive index changes in laser material. In addition, it is shown using computer-generated holograms that this device can detect phase discontinuities as well as improve the quality of sharp phase variations measurements. Results are compared to reference Shack-Hartmann measurements, and dramatic enhancements are obtained.

Enhanced sensitivity of surface plasmon resonance phase-interrogation biosensor by using oblique deposited silver nanorods.

PubMed

Chung, Hung-Yi; Chen, Chih-Chia; Wu, Pin Chieh; Tseng, Ming Lun; Lin, Wen-Chi; Chen, Chih-Wei; Chiang, Hai-Pang

2014-01-01

Sensitivity of surface plasmon resonance phase-interrogation biosensor is demonstrated to be enhanced by oblique deposited silver nanorods. Silver nanorods are thermally deposited on silver nanothin film by oblique angle deposition (OAD). The length of the nanorods can be tuned by controlling the deposition parameters of thermal deposition. By measuring the phase difference between the p and s waves of surface plasmon resonance heterodyne interferometer with different wavelength of incident light, we have demonstrated that maximum sensitivity of glucose detection down to 7.1 × 10(-8) refractive index units could be achieved with optimal deposition parameters of silver nanorods.

A Novel Phase Sensitive Quantum Well Nanostructure Scheme for Controlling Optical Bistability

NASA Astrophysics Data System (ADS)

Raheli, Ali

2018-04-01

A novel four-level lambda-type quantum well (QW) nanostructure is proposed based on phase sensitive optical bistability (OB) and multistability (OM) with a closed-loop configuration. The influence of controlling parameters of the system on OB and OM is investigated. In particular, it is found that the OB behavior is strongly sensitive to the relative phase of applied fields. It is also shown that under certain parametric conditions, the OB can be switched to OM or vice versa. The controllability of OB/OM in such a QW nanostructure may bring some new possibilities for technological applications in solid-state quantum information science and optoelectronics.

Nonuniform distribution of phase noise in distributed acoustic sensing based on phase-sensitive OTDR

NASA Astrophysics Data System (ADS)

Yu, Zhijie; Lu, Yang; Meng, Zhou

2017-10-01

A phase-sensitive optical time-domain reflectometry (∅-OTDR) implements distributed acoustic sensing (DAS) due to its ability for high sensitivity vibration measurement. Phase information of acoustic vibration events can be acquired by interrogation of the vibration-induced phase change between coherent Rayleigh scattering light from two points of the sensing fiber. And DAS can be realized when applying phase generated carrier (PGC) algorithm to the whole sensing fiber while the sensing fiber is transformed into a series of virtual sensing channels. Minimum detectable vibration of a ∅-OTDR is limited by phase noise level. In this paper, nonuniform distribution of phase noise of virtual sensing channels in a ∅-OTDR is investigated theoretically and experimentally. Correspondence between the intensity of Rayleigh scattering light and interference fading as well as polarization fading is analyzed considering inner interference of coherent Rayleigh light scattered from a multitude of scatters within pulse duration, and intensity noise related to the intensity of Rayleigh scattering light can be converted to phase noise while measuring vibration-induced phase change. Experiments are performed and the results confirm the predictions of the theoretical analysis. This study is essential for acquiring insight into nonuniformity of phase noise in DAS based on a ∅-OTDR, and would put forward some feasible methods to eliminate the effect of interference fading and polarization fading and optimize the minimum detectable vibration of a ∅-OTDR.

The influence of underwater turbulence on optical phase measurements

NASA Astrophysics Data System (ADS)

Redding, Brandon; Davis, Allen; Kirkendall, Clay; Dandridge, Anthony

2016-05-01

Emerging underwater optical imaging and sensing applications rely on phase-sensitive detection to provide added functionality and improved sensitivity. However, underwater turbulence introduces spatio-temporal variations in the refractive index of water which can degrade the performance of these systems. Although the influence of turbulence on traditional, non-interferometric imaging has been investigated, its influence on the optical phase remains poorly understood. Nonetheless, a thorough understanding of the spatio-temporal dynamics of the optical phase of light passing through underwater turbulence are crucial to the design of phase-sensitive imaging and sensing systems. To address this concern, we combined underwater imaging with high speed holography to provide a calibrated characterization of the effects of turbulence on the optical phase. By measuring the modulation transfer function of an underwater imaging system, we were able to calibrate varying levels of optical turbulence intensity using the Simple Underwater Imaging Model (SUIM). We then used high speed holography to measure the temporal dynamics of the optical phase of light passing through varying levels of turbulence. Using this method, we measured the variance in the amplitude and phase of the beam, the temporal correlation of the optical phase, and recorded the turbulence induced phase noise as a function of frequency. By bench marking the effects of varying levels of turbulence on the optical phase, this work provides a basis to evaluate the real-world potential of emerging underwater interferometric sensing modalities.

Phase-sensitive atomic dynamics in quantum light

NASA Astrophysics Data System (ADS)

Balybin, S. N.; Zakharov, R. V.; Tikhonova, O. V.

2018-05-01

Interaction between a quantum electromagnetic field and a model Ry atom with possible transitions to the continuum and to the low-lying resonant state is investigated. Strong sensitivity of atomic dynamics to the phase of applied coherent and squeezed vacuum light is found. Methods to extract the quantum field phase performing the measurements on the atomic system are proposed. In the case of the few-photon coherent state high accuracy of the phase determination is demonstrated, which appears to be much higher in comparison to the usually used quantum-optical methods such as homodyne detection.

Frequency dependence of sensitivities in second-order RC active filters

NASA Astrophysics Data System (ADS)

Kunieda, T.; Hiramatsu, Y.; Fukui, A.

1980-02-01

This paper presents that gain and phase sensitivities to some element in biquadratic filters approximately constitute a circle on the complex sensitivity plane, provided that the quality factor Q of the circuit is appreciably larger than unity. Moreover, the group delay sensitivity is represented by the imaginary part of a cardioid. Using these results, bounds of maximum values of gain, phase, and group delay sensitivities are obtained. Further, it is proved that the maximum values of these sensitivities can be simultaneously minimized by minimizing the absolute value of the transfer function sensitivity at the center frequency provided that w(0)-sensitivities are constant and do not contain design parameters. Next, a statistical variability measure for the optimal-filter design is proposed. Finally, the relation between some variability measures proposed to the present time is made clear.

Controlling Energy Radiations of Electromagnetic Waves via Frequency Coding Metamaterials.

PubMed

Wu, Haotian; Liu, Shuo; Wan, Xiang; Zhang, Lei; Wang, Dan; Li, Lianlin; Cui, Tie Jun

2017-09-01

Metamaterials are artificial structures composed of subwavelength unit cells to control electromagnetic (EM) waves. The spatial coding representation of metamaterial has the ability to describe the material in a digital way. The spatial coding metamaterials are typically constructed by unit cells that have similar shapes with fixed functionality. Here, the concept of frequency coding metamaterial is proposed, which achieves different controls of EM energy radiations with a fixed spatial coding pattern when the frequency changes. In this case, not only different phase responses of the unit cells are considered, but also different phase sensitivities are also required. Due to different frequency sensitivities of unit cells, two units with the same phase response at the initial frequency may have different phase responses at higher frequency. To describe the frequency coding property of unit cell, digitalized frequency sensitivity is proposed, in which the units are encoded with digits "0" and "1" to represent the low and high phase sensitivities, respectively. By this merit, two degrees of freedom, spatial coding and frequency coding, are obtained to control the EM energy radiations by a new class of frequency-spatial coding metamaterials. The above concepts and physical phenomena are confirmed by numerical simulations and experiments.

Visual motion modulates pattern sensitivity ahead, behind, and beside motion

PubMed Central

Arnold, Derek H.; Marinovic, Welber; Whitney, David

2014-01-01

Retinal motion can modulate visual sensitivity. For instance, low contrast drifting waveforms (targets) can be easier to detect when abutting the leading edges of movement in adjacent high contrast waveforms (inducers), rather than the trailing edges. This target-inducer interaction is contingent on the adjacent waveforms being consistent with one another – in-phase as opposed to out-of-phase. It has been suggested that this happens because there is a perceptually explicit predictive signal at leading edges of motion that summates with low contrast physical input – a ‘predictive summation’. Another possible explanation is a phase sensitive ‘spatial summation’, a summation of physical inputs spread across the retina (not predictive signals). This should be non-selective in terms of position – it should be evident at leading, adjacent, and at trailing edges of motion. To tease these possibilities apart, we examined target sensitivity at leading, adjacent, and trailing edges of motion. We also examined target sensitivity adjacent to flicker, and for a stimulus that is less susceptible to spatial summation, as it sums to grey across a small retinal expanse. We found evidence for spatial summation in all but the last condition. Finally, we examined sensitivity to an absence of signal at leading and trailing edges of motion, finding greater sensitivity at leading edges. These results are inconsistent with the existence of a perceptually explicit predictive signal in advance of drifting waveforms. Instead, we suggest that phase-contingent target-inducer modulations of sensitivity are explicable in terms of a directionally modulated spatial summation. PMID:24699250

Optimal packing for cascaded regenerative transmission based on phase sensitive amplifiers.

PubMed

Sorokina, Mariia; Sygletos, Stylianos; Ellis, Andrew D; Turitsyn, Sergei

2013-12-16

We investigate the transmission performance of advanced modulation formats in nonlinear regenerative channels based on cascaded phase sensitive amplifiers. We identify the impact of amplitude and phase noise dynamics along the transmission line and show that after a cascade of regenerators, densely packed single ring PSK constellations outperform multi-ring constellations. The results of this study will greatly simplify the design of future nonlinear regenerative channels for ultra-high capacity transmission.

Numerical modelling of distributed vibration sensor based on phase-sensitive OTDR

NASA Astrophysics Data System (ADS)

Masoudi, A.; Newson, T. P.

2017-04-01

A Distributed Vibration Sensor Based on Phase-Sensitive OTDR is numerically modeled. The advantage of modeling the building blocks of the sensor individually and combining the blocks to analyse the behavior of the sensing system is discussed. It is shown that the numerical model can accurately imitate the response of the experimental setup to dynamic perturbations a signal processing procedure similar to that used to extract the phase information from sensing setup.

Binaural interaction in low-frequency neurons in inferior colliculus of the cat. I. Effects of long interaural delays, intensity, and repetition rate on interaural delay function.

PubMed

Kuwada, S; Yin, T C

1983-10-01

Detailed, quantitative studies were made of the interaural phase sensitivity of 197 neurons with low best frequency in the inferior colliculus (IC) of the barbiturate-anesthetized cat. We analyzed the responses of single cells to interaural delays in which tone bursts were delivered to the two ears via sealed earphones and the onset of the tone to one ear with respect to the other was varied. For most (80%) cells the discharge rate is a cyclic function of interaural delay at a period corresponding to that of the stimulating frequency. The cyclic nature of the interaural delay curve indicates that these cells are sensitive to the interaural phase difference. These cells are distributed throughout the low-frequency zone of the IC, but they are less numerous in the medial and caudal zones. Cells with a wide variety of response patterns will exhibit interaural phase sensitivities at stimulating frequencies up to 3,100 Hz, although above 2,500 Hz the number of such cells decrease markedly. Using dichotic stimuli we could study the cell's sensitivity to the onset delay and interaural phase independently. The large majority of IC cells respond only to changes in interaural phase, with no sensitivity to the onset delay. However, a small number (7%) of cells exhibit a sensitivity to the onset delay as well as to the interaural phase disparity, and most of these cells show an onset response. The effects of changing the stimulus intensity equally to both ears or of changing the interaural intensity difference on the mean interaural phase were studied. While some neurons are not affected by level changes, others exhibit systematic phase shifts for both average and interaural intensity variations, and there is a continuous distribution of sensitivities between these extremes. A few cells also showed systematic changes in the shape of the interaural delay curves as a function of interaural intensity difference, especially at very long delays. These shifts can be interpreted as a form of time-intensity trading. A few cells demonstrated orderly changes in the interaural delay curve as the repetition rate of the stimulus was varied. Some of these changes are consonant with an inhibitory effect that occurs at stimulus offset. The responses of the neurons show a strong bias for stimuli that would originate from he contralateral sound field; 77% of the responses display mean interaural phase angles that are less than 0.5 of a cycle, which are delays to the ipsilateral tone.(ABSTRACT TRUNCATED AT 400 WORDS)

The Wigner–Yanase information can increase under phase sensitive incoherent operations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Du, Shuanping, E-mail: shuanpingdu@yahoo.com; Bai, Zhaofang, E-mail: baizhaofang@xmu.edu.cn

2015-08-15

We found that the Wigner-Yanase skew information, which has been recently proposed as a measure of coherence in Girolami (2014), can increase under a class of operations which may be interpreted as incoherent following the framework of Baumgratz et al., while being phase sensitive.

Constructing a High-Sensitivity, Computer-Interfaced, Differential Thermal Analysis Device for Teaching and Research

ERIC Educational Resources Information Center

Martinez, L. M.; Videa, M.; Mederos, F.; Mesquita, J.

2007-01-01

The construction of a new highly-sensitive, computer-interfaced, differential thermal analysis (DTA) device, used for gathering different information about the chemical reactions, is described. The instrument provides a better understanding about the phase transitions, phase diagrams and many more concepts to the students.

Lactococcus lactis NCC 2287 alleviates food allergic manifestations in sensitized mice by reducing IL-13 expression specifically in the ileum.

PubMed

Zuercher, Adrian W; Weiss, Marietta; Holvoet, Sébastien; Moser, Mireille; Moussu, Hélène; van Overtvelt, Laurence; Horiot, Stéphane; Moingeon, Philippe; Nutten, Sophie; Prioult, Guénolée; Singh, Anurag; Mercenier, Annick

2012-01-01

Utilizing a food allergy murine model, we have investigated the intrinsic antiallergic potential of the Lactococcus lactis NCC 2287 strain. BALB/c mice were sensitized at weekly intervals with ovalbumin (OVA) plus cholera toxin (CT) by the oral route for 7 weeks. In this model, an oral challenge with a high dose of OVA at the end of the sensitization period leads to clinical symptoms. Lactococcus lactis NCC 2287 was given to mice via the drinking water during sensitization (prevention phase) or after sensitization (management phase). Lactococcus lactis NCC 2287 administration to sensitized mice strikingly reduced allergic manifestations in the management phase upon challenge, when compared to control mice. No preventive effect was observed with the strain. Lactococcus lactis NCC 2287 significantly decreased relative expression levels of the Th-2 cytokine, IL-13, and associated chemokines CCL11 (eotaxin-1) and CCL17 (TARC) in the ileum. No effect was observed in the jejunum. These results taken together designate Lactococcus lactis NCC 2287 as a candidate probiotic strain appropriate in the management of allergic symptoms.

Characterization of beta phase growth and experimental validation of long term thermal exposure sensitization of AA5XXX alloys

NASA Astrophysics Data System (ADS)

Zhu, Yakun

The United States Navy has a need for fast, light-weight ships to provide rapid deployment in its operations. Strong and corrosion-resistant aluminum alloys, such as AA5083 (UNS A95083) as well as other AA5XXX alloys, have properties that are well-suited for such applications. However, AA5XXX alloys are susceptible to intergranular corrosion (IGC) and stress corrosion cracking (SCC) because of sensitization which is a consequence of the formation of the grain boundary beta-phase, Al3Mg2, and the anodic dissolution of the beta-phase. Significant research has been performed to measure and understand the effects of time, temperature, stress, and sea water on sensitization and associated intergranular corrosion and stress corrosion cracking under steady-state conditions. In the present work, the behaviors of beta-phase nucleation and growth were characterized using optical and electron microscopy, the relationship between preexisting particles and beta-phase, as well as the effect of different heat treatment times and temperatures on IGC and SCC susceptibility of 5XXX alloys were investigated. Grain boundary beta-phase thickness was measured with high resolution transmission electron microscopy (TEM). The corrosion sensitization susceptibility was evaluated according to the American Society for Testing and Materials (ASTM) standard G67 tests, that is, nitric acid mass-loss testing (NAMLT). Diffusion of Mg is manifested by the thickening of beta-phase along the grainboundary because the grain boundary is considered as the preferential site for beta-phase nucleation. The beta-phase growth rate was monitored using high resolution TEM. The variety of precipitates and their subsequent effects on beta-phase nucleation and growth kinetics was investigated. The existence of various intermetallic particles was observed in both baseline and thermally exposed (70°C and 175°C) samples. These particles are usually either rod-shaped or equiaxed, and rich in Mn, Fe, and Cr. Indexing of lattice planes observed in a few of these particles suggested the composition is Al6Mn or Al6(Mn, Fe, Cr). This research also shows that the beta-phase precipitation occurs between the preexisting Mn rich particles. The basic model for the determination of diffusivity values, the prediction of beta-phase thickness growth, and corrosion sensitization prediction have been improved by new data from this research.

The sensitivities of in cloud and cloud top phase distributions to primary ice formation in ICON-LEM

NASA Astrophysics Data System (ADS)

Beydoun, H.; Karrer, M.; Tonttila, J.; Hoose, C.

2017-12-01

Mixed phase clouds remain a leading source of uncertainty in our attempt to quantify cloud-climate and aerosol-cloud climate interactions. Nevertheless, recent advances in parametrizing the primary ice formation process, high resolution cloud modelling, and retrievals of cloud phase distributions from satellite data offer an excellent opportunity to conduct closure studies on the sensitivity of the cloud phase to microphysical and dynamical processes. Particularly, the reliability of satellite data to resolve the phase at the top of the cloud provides a promising benchmark to compare model output to. We run large eddy simulations with the new ICOsahedral Non-hydrostatic atmosphere model (ICON) to place bounds on the sensitivity of in cloud and cloud top phase to the primary ice formation process. State of the art primary ice formation parametrizations in the form of the cumulative ice active site density ns are implemented in idealized deep convective cloud simulations. We exploit the ability of ICON-LEM to switch between a two moment microphysics scheme and the newly developed Predicted Particle Properties (P3) scheme by running our simulations in both configurations for comparison. To quantify the sensitivity of cloud phase to primary ice formation, cloud ice content is evaluated against order of magnitude changes in ns at variable convective strengths. Furthermore, we assess differences between in cloud and cloud top phase distributions as well as the potential impact of updraft velocity on the suppression of the Wegener-Bergeron-Findeisen process. The study aims to evaluate our practical understanding of primary ice formation in the context of predicting the structure and evolution of mixed phase clouds.

Phase-sensitive spectral estimation by the hybrid filter diagonalization method.

PubMed

Celik, Hasan; Ridge, Clark D; Shaka, A J

2012-01-01

A more robust way to obtain a high-resolution multidimensional NMR spectrum from limited data sets is described. The Filter Diagonalization Method (FDM) is used to analyze phase-modulated data and cast the spectrum in terms of phase-sensitive Lorentzian "phase-twist" peaks. These spectra are then used to obtain absorption-mode phase-sensitive spectra. In contrast to earlier implementations of multidimensional FDM, the absolute phase of the data need not be known beforehand, and linear phase corrections in each frequency dimension are possible, if they are required. Regularization is employed to improve the conditioning of the linear algebra problems that must be solved to obtain the spectral estimate. While regularization smoothes away noise and small peaks, a hybrid method allows the true noise floor to be correctly represented in the final result. Line shape transformation to a Gaussian-like shape improves the clarity of the spectra, and is achieved by a conventional Lorentzian-to-Gaussian transformation in the time-domain, after inverse Fourier transformation of the FDM spectra. The results obtained highlight the danger of not using proper phase-sensitive line shapes in the spectral estimate. The advantages of the new method for the spectral estimate are the following: (i) the spectrum can be phased by conventional means after it is obtained; (ii) there is a true and accurate noise floor; and (iii) there is some indication of the quality of fit in each local region of the spectrum. The method is illustrated with 2D NMR data for the first time, but is applicable to n-dimensional data without any restriction on the number of time/frequency dimensions. Copyright © 2011. Published by Elsevier Inc.

Homodyning and heterodyning the quantum phase

NASA Technical Reports Server (NTRS)

Dariano, Giacomo M.; Macchiavello, C.; Paris, M. G. A.

1994-01-01

The double-homodyne and the heterodyne detection schemes for phase shifts between two synchronous modes of the electromagnetic field are analyzed in the framework of quantum estimation theory. The probability operator-valued measures (POM's) of the detectors are evaluated and compared with the ideal one in the limit of strong local reference oscillator. The present operational approach leads to a reasonable definition of phase measurement, whose sensitivity is actually related to the output r.m.s. noise of the photodetector. We emphasize that the simple-homodyne scheme does not correspond to a proper phase-shift measurements as it is just a zero-point detector. The sensitivity of all detection schemes are optimized at fixed energy with respect to the input state of radiation. It is shown that the optimal sensitivity can be actually achieved using suited squeezed states.

Magnetic flux density measurement with balanced steady state free precession pulse sequence for MREIT: a simulation study.

PubMed

Minhas, Atul S; Woo, Eung Je; Lee, Soo Yeol

2009-01-01

Magnetic Resonance Electrical Impedance Tomography (MREIT) utilizes the magnetic flux density B(z), generated due to current injection, to find conductivity distribution inside an object. This B(z) can be measured from MR phase images using spin echo pulse sequence. The SNR of B(z) and the sensitivity of phase produced by B(z) in MR phase image are critical in deciding the resolution of MREIT conductivity images. The conventional spin echo based data acquisition has poor phase sensitivity to current injection. Longer scan time is needed to acquire data with higher SNR. We propose a balanced steady state free precession (b-SSFP) based pulse sequence which is highly sensitive to small off-resonance phase changes. A procedure to reconstruct B(z) from MR signal obtained with b-SSFP sequence is described. Phases for b-SSFP signals for two conductivity phantoms of TX 151 and Gelatin are simulated from the mathematical models of b-SSFP signal. It was observed that the phase changes obtained from b-SSFP pulse sequence are highly sensitive to current injection and hence would produce higher magnetic flux density. However, the b-SSFP signal is dependent on magnetic field inhomogeneity and the signal deteriorated highly for small offset from resonance frequency. The simulation results show that the b-SSFP sequence can be utilized for conductivity imaging of a local region where magnetic field inhomogeneity is small. A proper shimming of magnet is recommended before using the b-SSFP sequence.

Physical measurement with in-line fiber Mach-Zehnder interferometer using differential phase white light interferometry

NASA Astrophysics Data System (ADS)

Aref, Seyed Hashem

2017-11-01

In this letter, the sensitivity to strain, curvature, and temperature of a sensor based on in-line fiber Mach-Zahnder interferometer (IFMZI) is studied and experimentally demonstrated. The sensing structure is simply a section of single mode fiber sandwiched between two abrupt tapers to achieve a compact IFMZI. The phase of interferometer changes with the measurand interaction, which is the basis for considering this structure for sensing. The physical parameter sensitivity of IFMZI sensor has been evaluated using differential white light interferometry (DWLI) technique as a phase read-out system. The differential configuration of the IFMZI sensor is used to achieve a high phase resolving power of ±0.062° for read-out interferometer by means of omission of phase noise of environment perturbations. The sensitivity of the sensor to the strain, curvature, and temperature has been measured 0.0199 degree/με, 757.00 degree/m-1, and 3.25 degree/°C, respectively.

Phase singularities in 3D plasmonic crystal metamaterials for ultra-sensitive biosensing

NASA Astrophysics Data System (ADS)

Danilov, Artem; Aristov, Andrey I.; Manousidaki, Maria; Terzaki, Konstantina; Fotakis, Costas; Farsari, Maria; Kabashin, Andrei V.

2017-02-01

Plasmonic biosensors form the core label-free technology for studies of biomolecular interactions, but they still need a drastic improvement of sensitivity and novel nano-architectural implementations to match modern trends of nanobiotechnology. Here, we consider the generation of resonances in light reflected from 3D woodpile plasmonic crystal metamaterials fabricated by Direct Laser Writing by Multi-Photon Polymerization, followed by silver electroless plating. We show that the generation of these resonances is accompanied by the appearance of singularities of phase of reflected light and examine the response of phase characteristics to refractive index variations inside the metamaterial matrix. The recorded phase sensitivity (3*104 deg. of phase shift per RIU change) outperforms most plasmonic counterparts and is attributed to particular conditions of plasmon excitation in 3D plasmonic crystal geometry. Combined with a large surface for biomolecular immobilizations offered by the 3D woodpile matrix, the proposed sensor architecture promises a new important landmark in the advancement of plasmonic biosensing technology.

Sensitivity and integration in a visual pathway for circadian entrainment in the hamster (Mesocricetus auratus).

PubMed Central

Nelson, D E; Takahashi, J S

1991-01-01

1. Light-induced phase shifts of the circadian rhythm of wheel-running activity were used to measure the photic sensitivity of a circadian pacemaker and the visual pathway that conveys light information to it in the golden hamster (Mesocricetus auratus). The sensitivity to stimulus irradiance and duration was assessed by measuring the magnitude of phase-shift responses to photic stimuli of different irradiance and duration. The visual sensitivity was also measured at three different phases of the circadian rhythm. 2. The stimulus-response curves measured at different circadian phases suggest that the maximum phase-shift is the only aspect of visual responsivity to change as a function of the circadian day. The half-saturation constants (sigma) for the stimulus-response curves are not significantly different over the three circadian phases tested. The photic sensitivity to irradiance (1/sigma) appears to remain constant over the circadian day. 3. The hamster circadian pacemaker and the photoreceptive system that subserves it are more sensitive to the irradiance of longer-duration stimuli than to irradiance of briefer stimuli. The system is maximally sensitive to the irradiance of stimuli of 300 s and longer in duration. A quantitative model is presented to explain the changes that occur in the stimulus-response curves as a function of photic stimulus duration. 4. The threshold for photic stimulation of the hamster circadian pacemaker is also quite high. The threshold irradiance (the minimum irradiance necessary to induce statistically significant responses) is approximately 10(11) photons cm-2 s-1 for optimal stimulus durations. This threshold is equivalent to a luminance at the cornea of 0.1 cd m-2. 5. We also measured the sensitivity of this visual pathway to the total number of photons in a stimulus. This system is maximally sensitive to photons in stimuli between 30 and 3600 s in duration. The maximum quantum efficiency of photic integration occurs in 300 s stimuli. 6. These results suggest that the visual pathways that convey light information to the mammalian circadian pacemaker possess several unique characteristics. These pathways are relatively insensitive to light irradiance and also integrate light inputs over relatively long durations. This visual system, therefore, possesses an optimal sensitivity of 'tuning' to total photons delivered in stimuli of several minutes in duration. Together these characteristics may make this visual system unresponsive to environmental 'noise' that would interfere with the entrainment of circadian rhythms to light-dark cycles. PMID:1895235

Effect of parameters in moving average method for event detection enhancement using phase sensitive OTDR

NASA Astrophysics Data System (ADS)

Kwon, Yong-Seok; Naeem, Khurram; Jeon, Min Yong; Kwon, Il-bum

2017-04-01

We analyze the relations of parameters in moving average method to enhance the event detectability of phase sensitive optical time domain reflectometer (OTDR). If the external events have unique frequency of vibration, then the control parameters of moving average method should be optimized in order to detect these events efficiently. A phase sensitive OTDR was implemented by a pulsed light source, which is composed of a laser diode, a semiconductor optical amplifier, an erbium-doped fiber amplifier, a fiber Bragg grating filter, and a light receiving part, which has a photo-detector and high speed data acquisition system. The moving average method is operated with the control parameters: total number of raw traces, M, number of averaged traces, N, and step size of moving, n. The raw traces are obtained by the phase sensitive OTDR with sound signals generated by a speaker. Using these trace data, the relation of the control parameters is analyzed. In the result, if the event signal has one frequency, then the optimal values of N, n are existed to detect the event efficiently.

Combined loading criterial influence on structural performance

NASA Technical Reports Server (NTRS)

Kuchta, B. J.; Sealey, D. M.; Howell, L. J.

1972-01-01

An investigation was conducted to determine the influence of combined loading criteria on the space shuttle structural performance. The study consisted of four primary phases: Phase (1) The determination of the sensitivity of structural weight to various loading parameters associated with the space shuttle. Phase (2) The determination of the sensitivity of structural weight to various levels of loading parameter variability and probability. Phase (3) The determination of shuttle mission loading parameters variability and probability as a function of design evolution and the identification of those loading parameters where inadequate data exists. Phase (4) The determination of rational methods of combining both deterministic time varying and probabilistic loading parameters to provide realistic design criteria. The study results are presented.

Optimal phase measurements with bright- and vacuum-seeded SU(1,1) interferometers

NASA Astrophysics Data System (ADS)

Anderson, Brian E.; Schmittberger, Bonnie L.; Gupta, Prasoon; Jones, Kevin M.; Lett, Paul D.

2017-06-01

The SU(1,1) interferometer can be thought of as a Mach-Zehnder interferometer with its linear beam splitters replaced with parametric nonlinear optical processes. We consider the cases of bright- and vacuum-seeded SU(1,1) interferometers using intensity or homodyne detectors. A simplified truncated scheme with only one nonlinear interaction is introduced, which not only beats conventional intensity detection with a bright seed, but can saturate the phase-sensitivity bound set by the quantum Fisher information. We also show that the truncated scheme achieves a sub-shot-noise phase sensitivity in the vacuum-seeded case, despite the phase-sensing optical beams having no well-defined phase.

Electrolytic lesions of a discrete area within the nucleus accumbens shell attenuate the long-term expression, but not early phase, of sensitization to cocaine.

PubMed

Brenhouse, Heather C; Montalto, Stefanie; Stellar, James R

2006-06-30

Repeated exposure to cocaine leads to behavioral sensitization, which is the augmentation of the locomotor response to a subsequent exposure to the drug. The nucleus accumbens (NAc), a major termination site of dopaminergic neurons, is believed to be involved in behavioral sensitization and studies have demonstrated that the NAc shell can be split into five zones of analysis; the vertex, arch, cone, intermediate and ventrolateral zones [Todtenkopf MS, Stellar JR. Assessment of tyrosine hydroxylase immunoreactive innervation in five subregions of the nucleus accumbens shell in rats treated with repeated cocaine. Synapse 2000;38:261-70]. Several reports show cocaine-induced c-fos expression particularly in the intermediate zone after 14, but not 2, drug-free days following repeated cocaine administration, suggesting that this region may be involved in sensitization and particularly in the later phase of expression, versus the earlier phase of sensitization. Bilateral electrolytic lesions of the intermediate zone were made in two groups of rats, which were then repeatedly exposed to cocaine (15 mg/kg, twice/day for 5 days). One group was subsequently given a single cocaine challenge injection (15 mg/kg) after 14 drug-free days, while the other group was challenged after only 2 drug-free days. Two sham surgery groups in which an electrode was lowered but no current was passed served as controls. Results show that lesioned animals as well as sham controls exhibited behavioral sensitization to the drug. However, following a 14-day drug-free period, the lesioned animals showed significant reduction in sensitization, compared to sham controls. Together these findings suggest that the intermediate zone of the NAc shell is indeed involved in the expression phase of behavioral sensitization to cocaine.

Quick, easy, cheap, effective, rugged, and safe sample preparation approach for pesticide residue analysis using traditional detectors in chromatography: A review.

PubMed

Rahman, Md Musfiqur; Abd El-Aty, A M; Kim, Sung-Woo; Shin, Sung Chul; Shin, Ho-Chul; Shim, Jae-Han

2017-01-01

In pesticide residue analysis, relatively low-sensitivity traditional detectors, such as UV, diode array, electron-capture, flame photometric, and nitrogen-phosphorus detectors, have been used following classical sample preparation (liquid-liquid extraction and open glass column cleanup); however, the extraction method is laborious, time-consuming, and requires large volumes of toxic organic solvents. A quick, easy, cheap, effective, rugged, and safe method was introduced in 2003 and coupled with selective and sensitive mass detectors to overcome the aforementioned drawbacks. Compared to traditional detectors, mass spectrometers are still far more expensive and not available in most modestly equipped laboratories, owing to maintenance and cost-related issues. Even available, traditional detectors are still being used for analysis of residues in agricultural commodities. It is widely known that the quick, easy, cheap, effective, rugged, and safe method is incompatible with conventional detectors owing to matrix complexity and low sensitivity. Therefore, modifications using column/cartridge-based solid-phase extraction instead of dispersive solid-phase extraction for cleanup have been applied in most cases to compensate and enable the adaptation of the extraction method to conventional detectors. In gas chromatography, the matrix enhancement effect of some analytes has been observed, which lowers the limit of detection and, therefore, enables gas chromatography to be compatible with the quick, easy, cheap, effective, rugged, and safe extraction method. For liquid chromatography with a UV detector, a combination of column/cartridge-based solid-phase extraction and dispersive solid-phase extraction was found to reduce the matrix interference and increase the sensitivity. A suitable double-layer column/cartridge-based solid-phase extraction might be the perfect solution, instead of a time-consuming combination of column/cartridge-based solid-phase extraction and dispersive solid-phase extraction. Therefore, replacing dispersive solid-phase extraction with column/cartridge-based solid-phase extraction in the cleanup step can make the quick, easy, cheap, effective, rugged, and safe extraction method compatible with traditional detectors for more sensitive, effective, and green analysis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Factors affecting the sensitivity of Tc-99m methoxyisobutylisonitrile dual-phase parathyroid single photon emission computed tomography in primary hyperparathyroidism.

PubMed

Araz, Mine; Çayir, Derya; Erdoğan, Mehmet; Uçan, Bekir; Çakal, Erman

2017-02-01

The aim of this study was to investigate the effects of thyroid diseases and regularly used medications on the sensitivity of Tc-99m methoxyisobutylisonitrile (MIBI) dual-phase parathyroid single photon emission computed tomography (SPECT) and to define indicatives of the result of the study. Overall, 218 primary hyperparathyroidism patients (190 women, 28 men, mean age: 57±14 years) with thyroid-parathyroid ultrasonography and Tc-99m MIBI dual-phase parathyroid SPECT were retrospectively enrolled. Patients were divided as follows: a positive SPECT group [119 (54.6%) patients] and a negative SPECT group [99 (45.4%) patients]. The effects of thyroid diseases and use of calcium channel blockers, β-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, oral antidiabetics, thyroid hormone preparates, nonsteroidal anti-inflammatory drugs, and proton pump inhibitors on the sensitivity of Tc-99m MIBI dual-phase parathyroid SPECT were investigated. The frequency of NSAID usage was higher in the negative scan group (P<0.001). No significant difference was detected in terms of coexisting thyroid disease or usage of other medications. Overall sensitivity, specificity, positive, and negative predictive value of Tc-99m MIBI dual-phase parathyroid SPECT were calculated to be 89.6, 92.5, 94.1, and 86.9%. The sensitivity was low only in nonsteroidal anti-inflammatory drug users (75.6%) compared with nonusers (96.5%). Logistic regression showed that ultrasonography was indicative of a positive scan and the possibility of a negative result was increased by regular usage of nonsteroid anti-inflammatory drugs (odds ratio: 0.262, confidence interval: 0.128-0.538; P<0.001) CONCLUSION: Among various drug groups, NSAIDs may decrease the sensitivity of Tc-99m MIBI SPECT and, provided that these novel data are supported by other studies, patient preparation may be modified to stop NSAIDs before Tc-99m MIBI dual-phase parathyroid SPECT.

Strategies to improve phase-stability of ultrafast swept source optical coherence tomography for single shot imaging of transient mechanical waves at 16 kHz frame rate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, Shaozhen; Wei, Wei; Hsieh, Bao-Yu

We present single-shot phase-sensitive imaging of propagating mechanical waves within tissue, enabled by an ultrafast optical coherence tomography (OCT) system powered by a 1.628 MHz Fourier domain mode-locked (FDML) swept laser source. We propose a practical strategy for phase-sensitive measurement by comparing the phases between adjacent OCT B-scans, where the B-scan contains a number of A-scans equaling an integer number of FDML buffers. With this approach, we show that micro-strain fields can be mapped with ∼3.0 nm sensitivity at ∼16 000 fps. The system's capabilities are demonstrated on porcine cornea by imaging mechanical wave propagation launched by a pulsed UV laser beam, promisingmore » non-contact, real-time, and high-resolution optical coherence elastography.« less

Interferometric sensitivity and entanglement by scanning through quantum phase transitions in spinor Bose-Einstein condensates

NASA Astrophysics Data System (ADS)

Feldmann, P.; Gessner, M.; Gabbrielli, M.; Klempt, C.; Santos, L.; Pezzè, L.; Smerzi, A.

2018-03-01

Recent experiments demonstrated the generation of entanglement by quasiadiabatically driving through quantum phase transitions of a ferromagnetic spin-1 Bose-Einstein condensate in the presence of a tunable quadratic Zeeman shift. We analyze, in terms of the Fisher information, the interferometric value of the entanglement accessible by this approach. In addition to the Twin-Fock phase studied experimentally, we unveil a second regime, in the broken axisymmetry phase, which provides Heisenberg scaling of the quantum Fisher information and can be reached on shorter time scales. We identify optimal unitary transformations and an experimentally feasible optimal measurement prescription that maximize the interferometric sensitivity. We further ascertain that the Fisher information is robust with respect to nonadiabaticity and measurement noise. Finally, we show that the quasiadiabatic entanglement preparation schemes admit higher sensitivities than dynamical methods based on fast quenches.

The temporal organization of processes of cell reproduction and its connection with rhythms of radiosensitivity of the body

NASA Technical Reports Server (NTRS)

Druzhinin, Y. P.; Romanov, Y. A.; Vatsek, A.

1974-01-01

Radiosensitivity of individual phases of the mitotic cycle was studied in synchronous cell cultures and in several biological objects. It was found that radiosensitivity changed essentially according to phases of the mitotic cycle, depending on the kind of cells, evaluation criteria and the radiation dosage. Tests on partially synchronized HeLa cell populations, according to the criterion of survival, showed them most sensitive during mitosis, as well as in later G sub 1- or early DNA-synthesizing stages. With radiation in doses of 300 rad, the proportion of surviving cells showed a sensitivity directly before DNA synthesis of approximately 4 times higher than the later S-phase and during the major portion of G sub 1- and G sub 2-periods. Sensitivity of cells in mitosis was approximately 3 times higher than in late G sub 1- and early S-phases.

3-dB signal-ASE beat noise reduction of coherent multi-carrier signal utilizing phase sensitive amplification.

PubMed

Umeki, Takeshi; Takara, Hidehiko; Miyamoto, Yutaka; Asobe, Masaki

2012-10-22

We demonstrated the simultaneous amplification of a coherent multi-carrier signal using a χ(2)-based non-degenerate phase sensitive amplifier (PSA). The signal-to-noise ratio (SNR), which is degraded by the additional amplified spontaneous emission (ASE) noise, can be recovered due to the gain difference between a phase-correlated signal-idler pair and uncorrelated excess noise. Utilizing the second harmonic pumping of a χ(2)-based PSA enables us to observe the SNR recovery directly by comparing the SNR for the input with that for the PSA output. A 3-dB optical-SNR (OSNR) improvement was obtained as a result of the gain difference. We also achieved a 3-dB SNR improvement in the electric domain by reducing the signal-ASE beat noise. The receiver sensitivity for a 10 Gbit/s phase shift keying signal was clearly improved with the PSA.

Chapter 5: Modulation Excitation Spectroscopy with Phase-Sensitive Detection for Surface Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shulda, Sarah; Richards, Ryan M.

Advancements in in situ spectroscopic techniques have led to significant progress being made in elucidating heterogeneous reaction mechanisms. The potential of these progressive methods is often limited only by the complexity of the system and noise in the data. Short-lived intermediates can be challenging, if not impossible, to identify with conventional spectra analysis means. Often equally difficult is separating signals that arise from active and inactive species. Modulation excitation spectroscopy combined with phase-sensitive detection analysis is a powerful tool for removing noise from the data while simultaneously revealing the underlying kinetics of the reaction. A stimulus is applied at amore » constant frequency to the reaction system, for example, a reactant cycled with an inert phase. Through mathematical manipulation of the data, any signal contributing to the overall spectra but not oscillating with the same frequency as the stimulus will be dampened or removed. With phase-sensitive detection, signals oscillating with the stimulus frequency but with various lag times are amplified providing valuable kinetic information. In this chapter, some examples are provided from the literature that have successfully used modulation excitation spectroscopy with phase-sensitive detection to uncover previously unobserved reaction intermediates and kinetics. Examples from a broad range of spectroscopic methods are included to provide perspective to the reader.« less

Controlling Energy Radiations of Electromagnetic Waves via Frequency Coding Metamaterials

PubMed Central

Wu, Haotian; Liu, Shuo; Wan, Xiang; Zhang, Lei; Wang, Dan; Li, Lianlin

2017-01-01

Metamaterials are artificial structures composed of subwavelength unit cells to control electromagnetic (EM) waves. The spatial coding representation of metamaterial has the ability to describe the material in a digital way. The spatial coding metamaterials are typically constructed by unit cells that have similar shapes with fixed functionality. Here, the concept of frequency coding metamaterial is proposed, which achieves different controls of EM energy radiations with a fixed spatial coding pattern when the frequency changes. In this case, not only different phase responses of the unit cells are considered, but also different phase sensitivities are also required. Due to different frequency sensitivities of unit cells, two units with the same phase response at the initial frequency may have different phase responses at higher frequency. To describe the frequency coding property of unit cell, digitalized frequency sensitivity is proposed, in which the units are encoded with digits “0” and “1” to represent the low and high phase sensitivities, respectively. By this merit, two degrees of freedom, spatial coding and frequency coding, are obtained to control the EM energy radiations by a new class of frequency‐spatial coding metamaterials. The above concepts and physical phenomena are confirmed by numerical simulations and experiments. PMID:28932671

Response of cat inferior colliculus neurons to binaural beat stimuli: possible mechanisms for sound localization.

PubMed

Kuwada, S; Yin, T C; Wickesberg, R E

1979-11-02

The interaural phase sensitivity of neurons was studied through the use of binaural beat stimuli. The response of most cells was phase-locked to the beat frequency, which provides a possible neural correlate to the human sensation of binaural beats. In addition, this stimulus allowed the direction and rate of interaural phase change to be varied. Some neurons in our sample responded selectively to manipulations of these two variables, which suggests a sensitivity to direction or speed of movement.

Sensitivity of Space Shuttle Weight and Cost to Structure Subsystem Weights

NASA Technical Reports Server (NTRS)

Wedge, T. E.; Williamson, R. P.

1973-01-01

Quantitative relationships between changes in space shuttle weights and costs with changes in weight of various portions of space shuttle structural subsystems are investigated. These sensitivity relationships, as they apply at each of three points in the development program (preliminary design phase, detail design phase, and test/operational phase) have been established for five typical space shuttle designs, each of which was responsive to the missions in the NASA Shuttle RFP, and one design was that selected by NASA.

Heterogeneous Sensitivity of Tropical Precipitation Extremes during Growth and Mature Phases of Atmospheric Warming

NASA Astrophysics Data System (ADS)

Parhi, P.; Giannini, A.; Lall, U.; Gentine, P.

2016-12-01

Assessing and managing risks posed by climate variability and change is challenging in the tropics, from both a socio-economic and a scientific perspective. Most of the vulnerable countries with a limited climate adaptation capability are in the tropics. However, climate projections, particularly of extreme precipitation, are highly uncertain there. The CMIP5 (Coupled Model Inter- comparison Project - Phase 5) inter-model range of extreme precipitation sensitivity to the global temperature under climate change is much larger in the tropics as compared to the extra-tropics. It ranges from nearly 0% to greater than 30% across models (O'Gorman 2012). The uncertainty is also large in historical gauge or satellite based observational records. These large uncertainties in the sensitivity of tropical precipitation extremes highlight the need to better understand how tropical precipitation extremes respond to warming. We hypothesize that one of the factors explaining the large uncertainty is due to differing sensitivities during different phases of warming. We consider the `growth' and `mature' phases of warming under climate variability case- typically associated with an El Niño event. In the remote tropics (away from tropical Pacific Ocean), the response of the precipitation extremes during the two phases can be through different pathways: i) a direct and fast changing radiative forcing in an atmospheric column, acting top-down due to the tropospheric warming, and/or ii) an indirect effect via changes in surface temperatures, acting bottom-up through surface water and energy fluxes. We also speculate that the insights gained here might be useful in interpreting the large sensitivity under climate change scenarios, since the physical mechanisms during the two warming phases under climate variability case, have some correspondence with an increasing and stabilized green house gas emission scenarios.

Upgrade for Phase II of the Gerda experiment

NASA Astrophysics Data System (ADS)

Agostini, M.; Bakalyarov, A. M.; Balata, M.; Barabanov, I.; Baudis, L.; Bauer, C.; Bellotti, E.; Belogurov, S.; Belyaev, S. T.; Benato, G.; Bettini, A.; Bezrukov, L.; Bode, T.; Borowicz, D.; Brudanin, V.; Brugnera, R.; Caldwell, A.; Cattadori, C.; Chernogorov, A.; D'Andrea, V.; Demidova, E. V.; Di Marco, N.; Domula, A.; Doroshkevich, E.; Egorov, V.; Falkenstein, R.; Frodyma, N.; Gangapshev, A.; Garfagnini, A.; Grabmayr, P.; Gurentsov, V.; Gusev, K.; Hakenmüller, J.; Hegai, A.; Heisel, M.; Hemmer, S.; Hiller, R.; Hofmann, W.; Hult, M.; Inzhechik, L. V.; Ioannucci, L.; Janicskó Csáthy, J.; Jochum, J.; Junker, M.; Kazalov, V.; Kermaïdic, Y.; Kihm, T.; Kirpichnikov, I. V.; Kirsch, A.; Kish, A.; Klimenko, A.; Kneißl, R.; Knöpfle, K. T.; Kochetov, O.; Kornoukhov, V. N.; Kuzminov, V. V.; Laubenstein, M.; Lazzaro, A.; Lebedev, V. I.; Lehnert, B.; Lindner, M.; Lippi, I.; Lubashevskiy, A.; Lubsandorzhiev, B.; Lutter, G.; Macolino, C.; Majorovits, B.; Maneschg, W.; Medinaceli, E.; Miloradovic, M.; Mingazheva, R.; Misiaszek, M.; Moseev, P.; Nemchenok, I.; Nisi, S.; Panas, K.; Pandola, L.; Pelczar, K.; Pullia, A.; Ransom, C.; Riboldi, S.; Rumyantseva, N.; Sada, C.; Salamida, F.; Salathe, M.; Schmitt, C.; Schneider, B.; Schönert, S.; Schreiner, J.; Schütz, A.-K.; Schulz, O.; Schwingenheuer, B.; Selivanenko, O.; Shevchik, E.; Shirchenko, M.; Simgen, H.; Smolnikov, A.; Stanco, L.; Vanhoefer, L.; Vasenko, A. A.; Veresnikova, A.; von Sturm, K.; Wagner, V.; Wegmann, A.; Wester, T.; Wiesinger, C.; Wojcik, M.; Yanovich, E.; Zhitnikov, I.; Zhukov, S. V.; Zinatulina, D.; Zsigmond, A. J.; Zuber, K.; Zuzel, G.

2018-05-01

The Gerda collaboration is performing a sensitive search for neutrinoless double beta decay of ^{76}Ge at the INFN Laboratori Nazionali del Gran Sasso, Italy. The upgrade of the Gerda experiment from Phase I to Phase II has been concluded in December 2015. The first Phase II data release shows that the goal to suppress the background by one order of magnitude compared to Phase I has been achieved. Gerda is thus the first experiment that will remain "background-free" up to its design exposure (100 kg year). It will reach thereby a half-life sensitivity of more than 10^{26} year within 3 years of data collection. This paper describes in detail the modifications and improvements of the experimental setup for Phase II and discusses the performance of individual detector components.

Benchmark On Sensitivity Calculation (Phase III)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ivanova, Tatiana; Laville, Cedric; Dyrda, James

2012-01-01

The sensitivities of the keff eigenvalue to neutron cross sections have become commonly used in similarity studies and as part of the validation algorithm for criticality safety assessments. To test calculations of the sensitivity coefficients, a benchmark study (Phase III) has been established by the OECD-NEA/WPNCS/EG UACSA (Expert Group on Uncertainty Analysis for Criticality Safety Assessment). This paper presents some sensitivity results generated by the benchmark participants using various computational tools based upon different computational methods: SCALE/TSUNAMI-3D and -1D, MONK, APOLLO2-MORET 5, DRAGON-SUSD3D and MMKKENO. The study demonstrates the performance of the tools. It also illustrates how model simplifications impactmore » the sensitivity results and demonstrates the importance of 'implicit' (self-shielding) sensitivities. This work has been a useful step towards verification of the existing and developed sensitivity analysis methods.« less

Sensitivity-Enhanced CMOS Phase Luminometry System Using Xerogel-Based Sensors.

PubMed

Lei Yao; Khan, R; Chodavarapu, V P; Tripathi, V S; Bright, F V

2009-10-01

We present the design and implementation of a phase luminometry sensor system with improved and tunable detection sensitivity achieved using a complementary metal-oxide semiconductor (CMOS) integrated circuit. We use sol-gel derived xerogel thin films as an immobilization media to house oxygen (O2) responsive luminescent molecules. The sensor operates on the principal of phase luminometry wherein a sinusoidal modulation signal is used to excite the luminophores encapsulated in the porous xerogel films and the corresponding phase shift of the emission signals is monitored. The phase shift is directly related to excited state lifetimes of the luminophores which in turn are related to the concentration of the target analyte species present in the vicinity of the luminophores. The CMOS IC, which consists of a 16 times 16 high-gain phototransistor array, current-to-voltage converter, amplifier and tunable phase shift detector, consumes an average power of 14 mW with 5-V power supply operating at a 38-kHz modulation frequency. The output of the IC is a dc voltage that corresponds to the detected luminescence phase shift with respect to the excitation signal. As a prototype, we demonstrate an oxygen sensor system by encapsulating the luminophore tris(4,7-diphenyl-1,10-phenanthroline)ruthenium(II) within the xerogel matrices. The sensor system showed a fast response on the order of few seconds and we obtained a detection sensitivity of 118 mV per 1% change in O2 concentration. The system demonstrates a novel concept to tune and improve the detection sensitivity for specific concentrations of the target analyte in many biomedical monitoring applications.

Profilometry of three-dimensional discontinuous solids by combining two-steps temporal phase unwrapping, co-phased profilometry and phase-shifting interferometry

NASA Astrophysics Data System (ADS)

Servin, Manuel; Padilla, Moises; Garnica, Guillermo; Gonzalez, Adonai

2016-12-01

In this work we review and combine two techniques that have been recently published for three-dimensional (3D) fringe projection profilometry and phase unwrapping, namely: co-phased profilometry and 2-steps temporal phase-unwrapping. By combining these two methods we get a more accurate, higher signal-to-noise 3D profilometer for discontinuous industrial objects. In single-camera single-projector (standard) profilometry, the camera and the projector must form an angle between them. The phase-sensitivity of the profilometer depends on this angle, so it cannot be avoided. This angle produces regions with self-occluding shadows and glare from the solid as viewed from the camera's perspective, making impossible the demodulation of the fringe-pattern there. In other words, the phase data is undefined at those shadow regions. As published recently, this limitation can be solved by using several co-phased fringe-projectors and a single camera. These co-phased projectors are positioned at different directions towards the object, and as a consequence most shadows are compensated. In addition to this, most industrial objects are highly discontinuous, which precludes the use of spatial phase-unwrappers. One way to avoid spatial unwrapping is to decrease the phase-sensitivity to a point where the demodulated phase is bounded to one lambda, so the need for phase-unwrapping disappears. By doing this, however, the recovered non-wrapped phase contains too much harmonic distortion and noise. Using our recently proposed two-step temporal phase-unwrapping technique, the high-sensitivity phase is unwrapped using the low-frequency one as initial gross estimation. This two-step unwrapping technique solves the 3D object discontinuities while keeping the accuracy of the high-frequency profilometry data. In scientific research, new art are derived as logical and consistent result of previous efforts in the same direction. Here we present a new 3D-profilometer combining these two recently published methods: co-phased profilometry and two-steps temporal phase-unwrapping. By doing this, we obtain a new and more powerful 3D profilometry technique which overcomes the two main limitations of previous fringe-projection profilometers namely: high phase-sensitivity digitalization of discontinuous objects and solid's self-generated shadow minimization. This new 3D profilometer is demonstrated by an experiment digitizing a discontinuous 3D industrial-solid where the advantages of this new profilometer with respect to previous art are clearly shown.

Phase I - Final report: Improved position sensitive detectors for thermal neutrons. Design, fabrication, and results of testing the Phase I - Proof-of-Principal Improved Position Sensitive Thermal Neutron Detector Prototype in the laboratory and at the Intense Pulsed Neutron Source (IPNS), Argonne National Laboratory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hull, Carter D.

A position sensitive neutron detector was designed and fabricated with bundles of individual detector elements with diameters of 120 mm. These neutron scintillating fibers were coupled with optoelectronic arrays to produce a ''Fiber Detector.'' A fiber position sensitive detector was completed and tested with scattered and thermal neutrons. Deployment of improved 2D PSDs with high signal to noise ratios at lower costs per area was the overall objective of the project.

Lactococcus lactis NCC 2287 Alleviates Food Allergic Manifestations in Sensitized Mice by Reducing IL-13 Expression Specifically in the Ileum

PubMed Central

Zuercher, Adrian W.; Weiss, Marietta; Holvoet, Sébastien; Moser, Mireille; Moussu, Hélène; van Overtvelt, Laurence; Horiot, Stéphane; Moingeon, Philippe; Nutten, Sophie; Prioult, Guénolée; Singh, Anurag; Mercenier, Annick

2012-01-01

Objective. Utilizing a food allergy murine model, we have investigated the intrinsic antiallergic potential of the Lactococcus lactis NCC 2287 strain. Methods. BALB/c mice were sensitized at weekly intervals with ovalbumin (OVA) plus cholera toxin (CT) by the oral route for 7 weeks. In this model, an oral challenge with a high dose of OVA at the end of the sensitization period leads to clinical symptoms. Lactococcus lactis NCC 2287 was given to mice via the drinking water during sensitization (prevention phase) or after sensitization (management phase). Results. Lactococcus lactis NCC 2287 administration to sensitized mice strikingly reduced allergic manifestations in the management phase upon challenge, when compared to control mice. No preventive effect was observed with the strain. Lactococcus lactis NCC 2287 significantly decreased relative expression levels of the Th-2 cytokine, IL-13, and associated chemokines CCL11 (eotaxin-1) and CCL17 (TARC) in the ileum. No effect was observed in the jejunum. Conclusion/Significance. These results taken together designate Lactococcus lactis NCC 2287 as a candidate probiotic strain appropriate in the management of allergic symptoms. PMID:21961022

Entangled-Pair Transmission Improvement Using Distributed Phase-Sensitive Amplification

NASA Astrophysics Data System (ADS)

Agarwal, Anjali; Dailey, James M.; Toliver, Paul; Peters, Nicholas A.

2014-10-01

We demonstrate the transmission of time-bin entangled photon pairs through a distributed optical phase-sensitive amplifier (OPSA). We utilize four-wave mixing at telecom wavelengths in a 5-km dispersion-shifted fiber OPSA operating in the low-gain limit. Measurements of two-photon interference curves show no statistically significant degradation in the fringe visibility at the output of the OPSA. In addition, coincidence counting rates are higher than direct passive transmission because of constructive interference between amplitudes of input photon pairs and those generated in the OPSA. Our results suggest that application of distributed phase-sensitive amplification to transmission of entangled photon pairs could be highly beneficial towards advancing the rate and scalability of future quantum communications systems.

The dream of a one-stop-shop: Meta-analysis on myocardial perfusion CT.

PubMed

Pelgrim, Gert Jan; Dorrius, Monique; Xie, Xueqian; den Dekker, Martijn A M; Schoepf, U Joseph; Henzler, Thomas; Oudkerk, Matthijs; Vliegenthart, Rozemarijn

2015-12-01

To determine the diagnostic performance of computed tomography (CT) perfusion techniques for the detection of functionally relevant coronary artery disease (CAD) in comparison to reference standards, including invasive coronary angiography (ICA), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI). PubMed, Web of Knowledge and Embase were searched from January 1, 1998 until July 1, 2014. The search yielded 9475 articles. After duplicate removal, 6041 were screened on title and abstract. The resulting 276 articles were independently analyzed in full-text by two reviewers, and included if the inclusion criteria were met. The articles reporting diagnostic parameters including true positive, true negative, false positive and false negative were subsequently evaluated for the meta-analysis. Results were pooled according to CT perfusion technique, namely snapshot techniques: single-phase rest, single-phase stress, single-phase dual-energy stress and combined coronary CT angiography [rest] and single-phase stress, as well the dynamic technique: dynamic stress CT perfusion. Twenty-two articles were included in the meta-analysis (1507 subjects). Pooled per-patient sensitivity and specificity of single-phase rest CT compared to rest SPECT were 89% (95% confidence interval [CI], 82-94%) and 88% (95% CI, 78-94%), respectively. Vessel-based sensitivity and specificity of single-phase stress CT compared to ICA-based >70% stenosis were 82% (95% CI, 64-92%) and 78% (95% CI, 61-89%). Segment-based sensitivity and specificity of single-phase dual-energy stress CT in comparison to stress MRI were 75% (95% CI, 60-85%) and 95% (95% CI, 80-99%). Segment-based sensitivity and specificity of dynamic stress CT perfusion compared to stress SPECT were 77% (95% CI, 67-85) and 89% (95% CI, 78-95%). For combined coronary CT angiography and single-phase stress CT, vessel-based sensitivity and specificity in comparison to ICA-based >50% stenosis were 84% (95% CI, 67-93%) and 93% (95% CI, 89-96%). This meta-analysis shows considerable variation in techniques and reference standards for CT of myocardial blood supply. While CT seems sensitive and specific for evaluation of hemodynamically relevant CAD, studies so far are limited in size. Standardization of myocardial perfusion CT technique is essential. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Laser-ablative engineering of phase singularities in plasmonic metamaterial arrays for biosensing applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aristov, Andrey I.; Kabashin, Andrei V., E-mail: kabashin@lp3.univ-mrs.fr; Zywietz, Urs

2014-02-17

By using methods of laser-induced transfer combined with nanoparticle lithography, we design and fabricate large-area gold nanoparticle-based metamaterial arrays exhibiting extreme Heaviside-like phase jumps in reflected light due to a strong diffractive coupling of localized plasmons. When employed in sensing schemes, these phase singularities provide the sensitivity of 5 × 10{sup 4} deg. of phase shift per refractive index unit change that is comparable with best values reported for plasmonic biosensors. The implementation of sensor platforms on the basis of such metamaterial arrays promises a drastic improvement of sensitivity and cost efficiency of plasmonic biosensing devices.

Determination of baryon-baryon elastic scattering phase shift from finite volume spectra in elongated boxes

NASA Astrophysics Data System (ADS)

Li, Ning; Wu, Ya-Jie; Liu, Zhan-Wei

2018-01-01

The relations between the baryon-baryon elastic scattering phase shifts and the two-particle energy spectrum in the elongated box are established. We studied the cases with both the periodic boundary condition and twisted boundary condition in the center of mass frame. The framework is also extended to the system of nonzero total momentum with periodic boundary condition in the moving frame. Moreover, we discussed the sensitivity functions σ (q ) that represent the sensitivity of higher scattering phases. Our analytical results will be helpful to extract the baryon-baryon elastic scattering phase shifts in the continuum from lattice QCD data by using elongated boxes.

DECIPHERING THERMAL PHASE CURVES OF DRY, TIDALLY LOCKED TERRESTRIAL PLANETS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koll, Daniel D. B.; Abbot, Dorian S., E-mail: dkoll@uchicago.edu

2015-03-20

Next-generation space telescopes will allow us to characterize terrestrial exoplanets. To do so effectively it will be crucial to make use of all available data. We investigate which atmospheric properties can, and cannot, be inferred from the broadband thermal phase curve of a dry and tidally locked terrestrial planet. First, we use dimensional analysis to show that phase curves are controlled by six nondimensional parameters. Second, we use an idealized general circulation model to explore the relative sensitivity of phase curves to these parameters. We find that the feature of phase curves most sensitive to atmospheric parameters is the peak-to-troughmore » amplitude. Moreover, except for hot and rapidly rotating planets, the phase amplitude is primarily sensitive to only two nondimensional parameters: (1) the ratio of dynamical to radiative timescales and (2) the longwave optical depth at the surface. As an application of this technique, we show how phase curve measurements can be combined with transit or emission spectroscopy to yield a new constraint for the surface pressure and atmospheric mass of terrestrial planets. We estimate that a single broadband phase curve, measured over half an orbit with the James Webb Space Telescope, could meaningfully constrain the atmospheric mass of a nearby super-Earth. Such constraints will be important for studying the atmospheric evolution of terrestrial exoplanets as well as characterizing the surface conditions on potentially habitable planets.« less

The Lemur Conjecture

NASA Astrophysics Data System (ADS)

Lanzagorta, Marco; Jitrik, Oliverio; Uhlmann, Jeffrey; Venegas-Andraca, Salvador E.

2017-05-01

In previous research we designed an interferometric quantum seismograph that uses entangled photon states to enhance sensitivity in an optomechanic device. However, a spatially-distributed array of such sensors, with each sensor measuring only nm-vibrations, may not provide sufficient sensitivity for the prediction of major earthquakes because it fails to exploit potentially critical phase information. We conjecture that relative phase information can explain the anecdotal observations that animals such as lemurs exhibit sensitivity to impending earthquakes earlier than can be done confidently with traditional seismic technology. More specifically, we propose that lemurs use their limbs as ground motion sensors and that relative phase differences are fused in the brain in a manner similar to a phased-array or synthetic-aperture radar. In this paper we will describe a lemur-inspired quantum sensor network for early warning of earthquakes. The system uses 4 interferometric quantum seismographs (e.g., analogous to a lemurs limbs) and then conducts phase and data fusion of the seismic information. Although we discuss a quantum-based technology, the principles described can also be applied to classical sensor arrays

Improved phase-ellipse method for in-situ geophone calibration.

USGS Publications Warehouse

Liu, Huaibao P.; Peselnick, L.

1986-01-01

For amplitude and phase response calibration of moving-coil electromagnetic geophones 2 parameters are needed, namely the geophone natural frequency, fo, and the geophone upper resonance frequency fu. The phase-ellipse method is commonly used for the in situ determination of these parameters. For a given signal-to-noise ratio, the precision of the measurement of fo and fu depends on the phase sensitivity, f(delta PHI/delta PHIf). For some commercial geophones (f(delta PHI/delta PHI) at fu can be an order of magnitude less than the sensitivity at fo. Presents an improved phase-ellipse method with increased precision. Compared to measurements made with the existing phase-ellipse methods, the method shows a 6- and 3-fold improvement in the precision, respectively, on measurements of fo and fu on a commercial geophone.-from Authors

Electrooptic modulation methods for high sensitivity tunable diode laser spectroscopy

NASA Technical Reports Server (NTRS)

Glenar, David A.; Jennings, Donald E.; Nadler, Shacher

1990-01-01

A CdTe phase modulator and low power RF sources have been used with Pb-salt tunable diode lasers operating near 8 microns to generate optical sidebands for high sensitivity absorption spectroscopy. Sweep averaged, first-derivative sample spectra of CH4 were acquired by wideband phase sensitive detection of the electrooptically (EO) generated carrier-sideband beat signal. EO generated beat signals were also used to frequency lock the TDL to spectral lines. This eliminates low frequency diode jitter, and avoids the excess laser linewidth broadening that accompanies TDL current modulation frequency locking methods.

Electrostatic Discharge Initiation Experiments using PVDF Pressure Transducers

DTIC Science & Technology

1991-12-01

ignition sensitivity. The results are discussed within the context of a preliminary model of electrostatic initiation. iii/iv NAVSWC TR 91-666 CONTENTS...Chapter Page 1 INTRODUCTION .......................................... 1-1 TWO PHASE IGNITION MODEL ....................... 1-1 SENSITIZING FACTORS...is necessary to establish effective techniques to reduce the hazards associated with ESD ignition. TWO-PHASE IGNITION MODEL A model has been proposed

Evaluation of beta-cell sensitivity to glucose and first-phase insulin secretion in obese dogs.

PubMed

Verkest, Kurt R; Fleeman, Linda M; Rand, Jacquie S; Morton, John M

2011-03-01

To compare beta-cell sensitivity to glucose, first-phase insulin secretion, and glucose tolerance between dogs with naturally occurring obesity of > 2 years' duration and lean dogs. 17 client-owned obese or lean dogs. Frequently sampled IV glucose tolerance tests were performed with minimal model analysis on 6 obese dogs and matched controls. Glucagon stimulation tests were performed on 5 obese dogs and matched controls. Obese dogs were half as sensitive to the effects of insulin as lean dogs. Plasma glucose concentrations after food withholding did not differ significantly between groups; plasma insulin concentrations were 3 to 4 times as great in obese as in lean dogs. Obese dogs had plasma insulin concentrations twice those of lean dogs after administration of glucose and 4 times as great after administration of glucagon. First-phase insulin secretion was greater in obese dogs. Obese dogs compensated for obesity-induced insulin resistance by secreting more insulin. First-phase insulin secretion and beta-cell glucose sensitivity were not lost despite years of obesity-induced insulin resistance and compensatory hyperinsulinemia. These findings help explain why dogs, unlike cats and humans, have not been documented to develop type 2 diabetes mellitus.

Probing non-unitary CP violation effects in neutrino oscillation experiments

NASA Astrophysics Data System (ADS)

Verma, Surender; Bhardwaj, Shankita

2018-05-01

In the present work, we have considered minimal unitarity violation scheme to obtain the general expression for ν _{μ }→ ν _{τ } oscillation probability in vacuum and matter. For this channel, we have investigated the sensitivities of short baseline experiments to non-unitary parameters |ρ _{μ τ }| and ω _{μ τ } for normal as well as inverted hierarchical neutrino masses and θ _{23} being above or below maximality. We find that for normal hierarchy, the 3σ sensitivity of |ρ _{μ τ }| is maximum for non-unitary phase ω _{μ τ }=0 whereas it is minimum for ω _{μ τ }=± π . For inverted hierarchy, the sensitivity is minimum at ω _{μ τ }=0 and maximum for ω _{μ τ }=± π . We observe that the sensitivity to measure non-unitarity remains unaffected for unitary CP phase δ =0 or δ =π /2 . We have, also, explored wide spectrum of L/E ratio to investigate the possibilities to observe CP-violation due to unitary (δ ) and non-unitary (ω _{μ τ } ) phases. We find that the both phases can be disentangled, in principle, from each other for L/E<200 km/GeV.

Safety and long-term immunological effects of CryJ2-LAMP plasmid vaccine in Japanese red cedar atopic subjects: A phase I study.

PubMed

Su, Yan; Romeu-Bonilla, Eliezer; Anagnostou, Athanasia; Fitz-Patrick, David; Hearl, William; Heiland, Teri

2017-12-02

Japanese Red Cedar (JRC) pollen induced allergy affects one third of Japanese and the development of effective therapies remains an unachieved challenge. We designed a DNA vaccine encoding CryJ2 allergen from the JRC pollen and Lysosomal Associated Membrane Protein 1 (LAMP-1) to treat JRC allergy. These Phase IA and IB trials assessed safety and immunological effects of the investigational CryJ2-LAMP DNA vaccine in both non-sensitive and sensitive Japanese expatriates living in Honolulu, Hawaii. In the Phase IA trial, 6 JRC non-sensitive subjects and 9 JRC and/or Mountain Cedar (MC) sensitive subjects were given 4 vaccine doses (each 4mg/1ml) intramuscularly (IM) at 14-day intervals. Nine JRC and/or MC sensitive subjects were given 4 doses (2 mg/0.5 ml) IM at 14-day intervals. The safety and functional biomarkers were followed for 132 d. Following this, 17 of 24 subjects were recruited into the IB trial and received one booster dose (2 mg/0.5 ml) IM approximately 300 d after the first vaccination dose to which they were randomized in the first phase of the trial. All safety endpoints were met and all subjects tolerated CryJ2-LAMP vaccinations well. At the end of the IA trial, 10 out of 12 JRC sensitive and 6 out of 11 MC sensitive subjects experienced skin test negative conversion, possibly related to the CryJ2-LAMP vaccinations. Collectively, these data suggested that the CryJ2-LAMP DNA vaccine is safe and may be immunologically effective in treating JRC induced allergy.

A Phase-Shifting Zernike Wavefront Sensor for the Palomar P3K Adaptive Optics System

NASA Technical Reports Server (NTRS)

Wallace, J. Kent; Crawford, Sam; Loya, Frank; Moore, James

2012-01-01

A phase-shifting Zernike wavefront sensor has distinct advantages over other types of wavefront sensors. Chief among them are: 1) improved sensitivity to low-order aberrations and 2) efficient use of photons (hence reduced sensitivity to photon noise). We are in the process of deploying a phase-shifting Zernike wavefront sensor to be used with the realtime adaptive optics system for Palomar. Here we present the current state of the Zernike wavefront sensor to be integrated into the high-order adaptive optics system at Mount Palomar's Hale Telescope.

Electromagnetic holographic sensitivity field of two-phase flow in horizontal wells

NASA Astrophysics Data System (ADS)

Zhang, Kuo; Wu, Xi-Ling; Yan, Jing-Fu; Cai, Jia-Tie

2017-03-01

Electromagnetic holographic data are characterized by two modes, suggesting that image reconstruction requires a dual-mode sensitivity field as well. We analyze an electromagnetic holographic field based on tomography theory and Radon inverse transform to derive the expression of the electromagnetic holographic sensitivity field (EMHSF). Then, we apply the EMHSF calculated by using finite-element methods to flow simulations and holographic imaging. The results suggest that the EMHSF based on the partial derivative of radius of the complex electric potential φ is closely linked to the Radon inverse transform and encompasses the sensitivities of the amplitude and phase data. The flow images obtained with inversion using EMHSF better agree with the actual flow patterns. The EMHSF overcomes the limitations of traditional single-mode sensitivity fields.

An Engineering Evaluation of Spherical Resorcinol Formaldehyde Resin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Birdwell Jr, Joseph F; Lee, Denise L; Taylor, Paul Allen

2010-09-01

A small column ion exchange (SCIX) system has been proposed for removal of cesium from caustic, supernatant, and dissolved salt solutions stored or generated from high-level tank wastes at the US Department of Energy (DOE) Hanford Site and Savannah River Sites. In both instances, deployment of SCIX systems, either in-tank or near-tank, is a means of expediting waste pretreatment and dispositioning with minimal or no new infrastructure requirements. Conceptually, the treatment approach can utilize a range of ion exchange media. Previously, both crystalline silicotitanate (CST), an inorganic, nonelutable sorbent, and resorcinol-formaldehyde (RF), an organic, elutable resin, have been considered formore » cesium removal from tank waste. More recently, Pacific Northwest National Laboratory (PNNL) evaluated use of SuperLig{reg_sign} 644, an elutable ion exchange medium, for the subject application. Results of testing indicate hydraulic limitations of the SuperLig{reg_sign} resin, specifically a high pressure drop through packed ion exchange columns. This limitation is likely the result of swelling and shrinkage of the irregularly shaped (granular) resin during repeated conversions between sodium and hydrogen forms as the resin is first loaded then eluted. It is anticipated that a similar flow limitation would exist in columns packed with conventional, granular RF resin. However, use of spherical RF resin is a likely means of mitigating processing limitations due to excessive pressure drop. Although size changes occur as the spherical resin is cycled through loading and elution operations, the geometry of the resin is expected to effectively mitigate the close packing that leads to high pressure drops across ion exchange columns. Multiple evaluations have been performed to determine the feasibility of using spherical RF resin and to obtain data necessary for design of an SCIX process. The work performed consisted of examination of radiation effects on resin performance, quantification of cesium adsorption performance as a function of operating temperature and pH, and evaluation of sodium uptake (titration) as function of pH and counteranion concentration. The results of these efforts are presented in this report. Hydraulic performance of the resin and the use of eluant alternatives to nitric acid have also been evaluated and have been reported elsewhere (Taylor 2009, Taylor and Johnson 2009).« less

An analytical SMASH procedure (ASP) for sensitivity-encoded MRI.

PubMed

Lee, R F; Westgate, C R; Weiss, R G; Bottomley, P A

2000-05-01

The simultaneous acquisition of spatial harmonics (SMASH) method of imaging with detector arrays can reduce the number of phase-encoding steps, and MRI scan time several-fold. The original approach utilized numerical gradient-descent fitting with the coil sensitivity profiles to create a set of composite spatial harmonics to replace the phase-encoding steps. Here, an analytical approach for generating the harmonics is presented. A transform is derived to project the harmonics onto a set of sensitivity profiles. A sequence of Fourier, Hilbert, and inverse Fourier transform is then applied to analytically eliminate spatially dependent phase errors from the different coils while fully preserving the spatial-encoding. By combining the transform and phase correction, the original numerical image reconstruction method can be replaced by an analytical SMASH procedure (ASP). The approach also allows simulation of SMASH imaging, revealing a criterion for the ratio of the detector sensitivity profile width to the detector spacing that produces optimal harmonic generation. When detector geometry is suboptimal, a group of quasi-harmonics arises, which can be corrected and restored to pure harmonics. The simulation also reveals high-order harmonic modulation effects, and a demodulation procedure is presented that enables application of ASP to a large numbers of detectors. The method is demonstrated on a phantom and humans using a standard 4-channel phased-array MRI system. Copyright 2000 Wiley-Liss, Inc.

Early-Phase 11C-PiB PET in Amyloid Angiopathy-Related Symptomatic Cerebral Hemorrhage: Potential Diagnostic Value?

PubMed Central

Aigbirhio, Franklin I.; Fryer, Tim D.; Menon, David K.; Warburton, Elizabeth A.; Baron, Jean-Claude

2015-01-01

Although late-phase (>35min post-administration) 11C-PiB-PET has good sensitivity in cerebral amyloid angiopathy (CAA), its specificity is poor due to frequently high uptake in healthy aged subjects. By detecting perfusion-like abnormalities, early-phase 11C-PiB-PET might add diagnostic value. Early-frame (1–6min) 11C-PiB-PET was obtained in 11 non-demented patients with probable CAA-related symptomatic lobar intracerebral haemorrhage (70±7yrs), 9 age-matched healthy controls (HCs) and 10 HCs <55yrs. There was a significant decrease in early-phase atrophy-corrected whole-cortex SUV relative to cerebellar vermis (SUVR) in the CAA vs age-matched HC group. None of the age-matched controls fell below the lower 95% confidence limit derived from the young HCs, while 6/11 CAA patients did (sensitivity = 55%, specificity = 100%). Combining both early- and late-phase 11C-PiB data did not change the sensitivity and specificity of late-phase PiB, but combined early- and late-phase positivity entails a very high suspicion of underlying Aβ-related clinical disorder, i.e., CAA or Alzheimer disease (AD). In order to clarify this ambiguity, we then show that the occipital/posterior cingulate ratio is markedly lower in CAA than in AD (N = 7). These pilot data suggest that early-phase 11C-PiB-PET may not only add to late-phase PiB-PET with respect to the unclear situation of late-phase positivity, but also help differentiate CAA from AD. PMID:26439113

Emergence of multiple synchronization modes in hydrodynamically-coupled cilia

NASA Astrophysics Data System (ADS)

Guo, Hanliang; Kanso, Eva

2016-11-01

Motile cilia and flagella exhibit different phase coordinations. For example, closely swimming spermatozoa are observed to synchronize together; bi-flagellates Chlamydomonas regulate the flagella in a "breast-stroke" fashion; cilia on the surface of Paramecium beat in a fixed phase lag in an orchestrated wave like fashion. Experimental evidence suggests that phase coordinations can be achieved solely via hydrodynamical interactions. However, the exact mechanisms behind it remain illusive. Here, adapting a "geometric switch" model, we observe different synchronization modes in pairs of hydrodynamically-coupled cilia by changing physical parameters such as the strength of the cilia internal motor and the separation distance between cilia. Interestingly, we find regions in the parameter space where the coupled cilia reach stable phase coordinations and regions where the phase coordinations are sensitive to perturbations. We also find that leaning into the fluid reduces the sensitivity to perturbations, and produces stable phase coordination that is neither in-phase nor anti-phase, which could explain the origin of metachronal waves in large cilia populations.

Effect of ZCR-2060, an antiallergic agent, on antigen-induced immediate- and late-phase increases in airway resistance in sensitized guinea pigs.

PubMed

Abe, T; Yoshida, K; Omata, T; Segawa, Y; Matsuda, K; Nagai, H

1995-01-01

The effect of 2-[2-[4-(diphenylmethyl)-1-piperadinyl]ethoxy] benzoic acid maleate (ZCR-2060) on passive systemic anaphylaxis (PSA) and antigen-induced immediate- and late-phase increase in airway resistance (Rrs) in either passively or actively sensitized guinea pigs were investigated. ZCR-2060 inhibited PSA in guinea pigs. ID50 values of ZCR-2060, ketotifen, terfenadine and cetirizine on PSA were 0.03, 0.02, 0.8 and 0.3 mg/kg, respectively, when administered orally 1 h before the antigen challenge. The protective effect of ZCR-2060 was observed until 12 h before the antigen challenge. Aeroantigen-induce immediate increase in Rrs in passively sensitized guinea pigs with and without metyrapone treatment was inhibited by ZCR-2060, ketotifen, terfenadine and cetirizine. In contrast, prednisolone did not affect the aeroantigen-induced immediate increase in Rrs in animals not treated with metyrapone, but significantly inhibited the metyrapone-induced enhanced immediate response. In actively sensitized animals, the immediate- and late-phase increases in Rrs were observed within 30 min and between 3 and 8 h after the aeroantigen challenge. Pretreatment with metyrapone accelerated both antigen-induced responses. ZCR-2060 (1 mg/kg) significantly inhibited both responses. Ketotifen (1 mg/kg), terfenadine (10 mg/kg) and prednisolone (10 mg/kg) significantly the inhibited the late-phase response, but did not affect the immediate-phase response. In contrast, Cetirizine (10 mg/kg) did not affect either response. The effect of ZCR-2060 on late-phase response was stronger than that of ketotifen, terfenadine and cetirizine, and was almost the same as that of prednisolone. These results suggest that ZCR-2060 has a potent protective effect on immediate- and late-phase increases in Rrs.

Study on ABO and RhD blood grouping: Comparison between conventional tile method and a new solid phase method (InTec Blood Grouping Test Kit).

PubMed

Yousuf, R; Abdul Ghani, S A; Abdul Khalid, N; Leong, C F

2018-04-01

'InTec Blood Grouping Test kit' using solid-phase technology is a new method which may be used at outdoor blood donation site or at bed side as an alternative to the conventional tile method in view of its stability at room temperature and fulfilled the criteria as point of care test. This study aimed to compare the efficiency of this solid phase method (InTec Blood Grouping Test Kit) with the conventional tile method in determining the ABO and RhD blood group of healthy donors. A total of 760 voluntary donors who attended the Blood Bank, Penang Hospital or offsite blood donation campaigns from April to May 2014 were recruited. The ABO and RhD blood groups were determined by the conventional tile method and the solid phase method, in which the tube method was used as the gold standard. For ABO blood grouping, the tile method has shown 100% concordance results with the gold standard tube method, whereas the solid-phase method only showed concordance result for 754/760 samples (99.2%). Therefore, for ABO grouping, tile method has 100% sensitivity and specificity while the solid phase method has slightly lower sensitivity of 97.7% but both with good specificity of 100%. For RhD grouping, both the tile and solid phase methods have grouped one RhD positive specimen as negative each, thus giving the sensitivity and specificity of 99.9% and 100% for both methods respectively. The 'InTec Blood Grouping Test Kit' is suitable for offsite usage because of its simplicity and user friendliness. However, further improvement in adding the internal quality control may increase the test sensitivity and validity of the test results.

A rapid enhancement of locomotor sensitization to amphetamine by estradiol in female rats.

PubMed

Zovkic, Iva B; McCormick, Cheryl M

2017-11-14

Estradiol moderates the effects of drugs of abuse in both humans and rodents. Estradiol's enhancement of behavioral effects resulting from high (>2.5mg/kg) doses of amphetamine is established in rats; there is less evidence for the role of estradiol in locomotor effects elicited by lower doses, which are less aversive, increase incentive motivation, involve different neural mechanisms than higher doses, and often more readily reveal group differences than do higher doses. Further, the extent to which estradiol is required for the induction versus the expression of sensitization is unknown. To establish a protocol, we replicated the effects of estradiol on locomotor sensitization to amphetamine reported in a previous study that involved a high locomotor-activating dose (1.5mg/kg) of amphetamine, but with a lower dose. Ovariectomized female rats received 5μg of estradiol benzoate (EB) or OIL 30min before each of 5 treatments of 1.0mg/kg amphetamine or saline; all received a 0.5mg/kg challenge dose three days later. Compared with results for OIL, EB enhanced the locomotor-activating effects of repeated 1.0mg/kg amphetamine across treatment days. In contrast, on challenge day, there was no difference between EB-saline and EB-amphetamine to the lower dose (i.e., no sensitization). Experiments 2 and 3 involved a shorter induction (2days) and a lengthier withdrawal (9days) before the challenge test for the expression of sensitization to better differentiate the induction phase from the expression phase. In Expt2, EB-, and not OIL-, treated rats showed sensitization to 0.5mg/kg amphetamine; neither group showed sensitization to 1.5mg/kg amphetamine (ceiling effect?). In Expt3, rats were treated with EB either in both the induction and expression phases, in one of the phases only, or in neither phase. There was an effect of hormone treatment on challenge day and not on induction day; rats given EB on Challenge day showed sensitization to 0.5mg/kg amphetamine; OIL rats did not. The results suggest rapid effects of estradiol on amphetamine sensitization consistent with rapid effects of estradiol reported for other behaviours. Copyright © 2017. Published by Elsevier Inc.

Sensitive bridge circuit measures conductance of low-conductivity electrolyte solutions

NASA Technical Reports Server (NTRS)

Schmidt, K.

1967-01-01

Compact bridge circuit measures sensitive and accurate conductance of low-conductivity electrolyte solutions. The bridge utilizes a phase sensitive detector to obtain a linear deflection of the null indicator relative to the measured conductance.

Dynamical Model of Drug Accumulation in Bacteria: Sensitivity Analysis and Experimentally Testable Predictions

DOE PAGES

Vesselinova, Neda; Alexandrov, Boian; Wall, Michael E.

2016-11-08

We present a dynamical model of drug accumulation in bacteria. The model captures key features in experimental time courses on ofloxacin accumulation: initial uptake; two-phase response; and long-term acclimation. In combination with experimental data, the model provides estimates of import and export rates in each phase, the time of entry into the second phase, and the decrease of internal drug during acclimation. Global sensitivity analysis, local sensitivity analysis, and Bayesian sensitivity analysis of the model provide information about the robustness of these estimates, and about the relative importance of different parameters in determining the features of the accumulation time coursesmore » in three different bacterial species: Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. The results lead to experimentally testable predictions of the effects of membrane permeability, drug efflux and trapping (e.g., by DNA binding) on drug accumulation. A key prediction is that a sudden increase in ofloxacin accumulation in both E. coli and S. aureus is accompanied by a decrease in membrane permeability.« less

Balancing Methodological Rigor and the Needs of Research Participants: A Debate on Alternative Approaches to Sensitive Research.

PubMed

Chan, T M Simon; Teram, Eli; Shaw, Ian

2017-01-01

Despite growing consideration of the needs of research participants in studies related to sensitive issues, discussions of alternative ways to design sensitive research are scarce. Structured as an exchange between two researchers who used different approaches in their studies with childhood sexual abuse survivors, in this article, we seek to advance understanding of methodological and ethical issues in designing sensitive research. The first perspective, which is termed protective, promotes the gradual progression of participants from a treatment phase into a research phase, with the ongoing presence of a researcher and a social worker in both phases. In the second perspective, which is termed minimalist, we argue for clear boundaries between research and treatment processes, limiting the responsibility of researchers to ensuring that professional support is available to participants who experience emotional difficulties. Following rebuttals, lessons are drawn for ethical balancing between methodological rigor and the needs of participants. © The Author(s) 2015.

Dynamical Model of Drug Accumulation in Bacteria: Sensitivity Analysis and Experimentally Testable Predictions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vesselinova, Neda; Alexandrov, Boian; Wall, Michael E.

We present a dynamical model of drug accumulation in bacteria. The model captures key features in experimental time courses on ofloxacin accumulation: initial uptake; two-phase response; and long-term acclimation. In combination with experimental data, the model provides estimates of import and export rates in each phase, the time of entry into the second phase, and the decrease of internal drug during acclimation. Global sensitivity analysis, local sensitivity analysis, and Bayesian sensitivity analysis of the model provide information about the robustness of these estimates, and about the relative importance of different parameters in determining the features of the accumulation time coursesmore » in three different bacterial species: Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. The results lead to experimentally testable predictions of the effects of membrane permeability, drug efflux and trapping (e.g., by DNA binding) on drug accumulation. A key prediction is that a sudden increase in ofloxacin accumulation in both E. coli and S. aureus is accompanied by a decrease in membrane permeability.« less

High sensitivity pressure transducer based on the phase characteristics of GMI magnetic sensors

NASA Astrophysics Data System (ADS)

Benavides, L. S.; Costa Silva, E.; Costa Monteiro, E.; Hall Barbosa, C. R.

2018-03-01

This paper presents a new configuration for a GMI pressure transducer based on the reading of the phase characteristics of GMI sensor, intended for biomedical applications. The development process of this new class of magnetic field transducers is discussed, beginning with the definition of the ideal conditioning of the GMI sensor elements (dc level and frequency of the excitation current and sample length) and continuing with computational simulations of the full electronic circuit performed using the experimental data obtained from measured GMI curves, and have shown that the improvement in the sensitivity of GMI magnetometers is larger when phase-based transducers are used instead of magnitude-based transducers. Parameters of interest of the developed prototype are thoroughly analyzed, such as: sensitivity, linearity and frequency response. Also, the spectral noise density of the developed pressure transducer is evaluated and its resolution in the passband is estimated. A low-cost GMI pressure transducer was developed, presenting high resolution, high sensitivity and a frequency bandwidth compatible to the desired biomedical applications.

Phase-Shifting Zernike Interferometer Wavefront Sensor

NASA Technical Reports Server (NTRS)

Wallace, J. Kent; Rao, Shanti; Jensen-Clemb, Rebecca M.; Serabyn, Gene

2011-01-01

The canonical Zernike phase-contrast technique1,2,3,4 transforms a phase object in one plane into an intensity object in the conjugate plane. This is done by applying a static pi/2 phase shift to the central core (approx. lambda/D) of the PSF which is intermediate between the input and output planes. Here we present a new architecture for this sensor. First, the optical system is simple and all reflective. Second, the phase shift in the central core of the PSF is dynamic and or arbitrary size. This common-path, all-reflective design makes it minimally sensitive to vibration, polarization and wavelength. We review the theory of operation, describe the optical system, summarize numerical simulations and sensitivities and review results from a laboratory demonstration of this novel instrument

Phase-Shifting Zernike Interferometer Wavefront Sensor

NASA Technical Reports Server (NTRS)

Wallace, J. Kent; Rao, Shanti; Jensen-Clem, Rebecca M.

2011-01-01

The canonical Zernike phase-contrast technique transforms a phase object in one plane into an intensity object in the conjugate plane. This is done by applying a static pi/2 phase shift to the central core (approx. lambda/diameter) of the PSF which is intermediate between the input and output plane. Here we present a new architecture for this sensor. First, the optical system is simple and all reflective, and second the phase shift in the central core of the PSF is dynamic and can be made arbitrarily large. This common-path, all-reflective design makes it minimally sensitive to vibration, polarization and wavelength. We review the theory of operation, describe the optical system, summarize numerical simulations and sensitivities and review results from a laboratory demonstration of this novel instrument.

A method to calibrate phase fluctuation in polarization-sensitive swept-source optical coherence tomography

NASA Astrophysics Data System (ADS)

Lu, Zenghai; Kasaragod, Deepa K.; Matcher, Stephen J.

2011-06-01

A phase fluctuation calibration method is presented for polarization-sensitive swept-source optical coherence tomography (PS-SS-OCT) using continuous polarization modulation. The method consists of the generation of a continuous triggered tone-burst waveform rather than an asynchronous waveform by use of a function generator and the removal of the global phases of the measured Jones matrices by use of matrix normalization. This could remove the use of auxiliary optical components for the phase fluctuation compensation in the system, which reduces the system complexity. Phase fluctuation calibration is necessary to obtain the reference Jones matrix by averaging the measured Jones matrices at sample surfaces. Measurements on an equine tendon sample were made by the PS-SS-OCT system to validate the proposed method.

Design of a sensitive grating-based phase contrast mammography prototype (Conference Presentation)

NASA Astrophysics Data System (ADS)

Arboleda Clavijo, Carolina; Wang, Zhentian; Köhler, Thomas; van Stevendaal, Udo; Martens, Gerhard; Bartels, Matthias; Villanueva-Perez, Pablo; Roessl, Ewald; Stampanoni, Marco

2017-03-01

Grating-based phase contrast mammography can help facilitate breast cancer diagnosis, as several research works have demonstrated. To translate this technique to the clinics, it has to be adapted to cover a large field of view within a limited exposure time and with a clinically acceptable radiation dose. This indicates that a straightforward approach would be to install a grating interferometer (GI) into a commercial mammography device. We developed a wave propagation based optimization method to select the most convenient GI designs in terms of phase and dark-field sensitivities for the Philips Microdose Mammography (PMM) setup. The phase sensitivity was defined as the minimum detectable breast tissue electron density gradient, whereas the dark-field sensitivity was defined as its corresponding signal-to-noise Ratio (SNR). To be able to derive sample-dependent sensitivity metrics, a visibility reduction model for breast tissue was formulated, based on previous research works on the dark-field signal and utilizing available Ultra-Small-Angle X-ray Scattering (USAXS) data and the outcomes of measurements on formalin-fixed breast tissue specimens carried out in tube-based grating interferometers. The results of this optimization indicate the optimal scenarios for each metric are different and fundamentally depend on the noise behavior of the signals and the visibility reduction trend with respect to the system autocorrelation length. In addition, since the inter-grating distance is constrained by the space available between the breast support and the detector, the best way we have to improve sensitivity is to count on a small G2 pitch.

Low Dose High Energy X-ray In-Line Phase Sensitive Imaging Prototype: Investigation of Optimal Geometric Conditions and Design Parameters

PubMed Central

Ghani, Muhammad. U.; Yan, Aimin; Wong, Molly. D.; Li, Yuhua; Ren, Liqiang; Wu, Xizeng; Liu, Hong

2016-01-01

The objective of this study was to investigate the optimization of a high energy in-line phase sensitive x-ray imaging prototype under different geometric and operating conditions for mammography application. A phase retrieval algorithm based on phase attenuation duality (PAD) was applied to the phase contrast images acquired by the prototype. Imaging performance was investigated at four magnification values of 1.67, 2, 2.5 and 3 using an acrylic edge, an American College of Radiology (ACR) mammography phantom and contrast detail (CD) phantom with tube potentials of 100, 120 and 140 kVp. The ACR and CD images were acquired at the same mean glandular dose (MGD) of 1.29 mGy with a computed radiography (CR) detector of 43.75 µm pixel pitch at a fixed source to image distance (SID) of 170 cm. The x-ray tube focal spot size was kept constant as 7 µm while a 2.5 mm thick aluminum (Al) filter was used for beam hardening. The performance of phase contrast and phase retrieved images were compared with computer simulations based on the relative phase contrast factor (RPF) at high x-ray energies. The imaging results showed that the x-ray tube operated at 100 kVp under the magnification of 2.5 exhibits superior imaging performance which is in accordance to the computer simulations. As compared to the phase contrast images, the phase retrieved images of the ACR and CD phantoms demonstrated improved imaging contrast and target discrimination. We compared the CD phantom images acquired in conventional contact mode with and without the anti-scatter grid using the same prototype at 1.295 mGy and 2.59 mGy using 40 kVp, a 25 µm rhodium (Rh) filter. At the same radiation dose, the phase sensitive images provided improved detection capabilities for both the large and small discs, while compared to the double dose image acquired in conventional mode, the observer study also indicated that the phase sensitive images provided improved detection capabilities for the large discs. This study therefore validates the potential of using high energy phase contrast x-ray imaging to improve lesion detection and reduce radiation dose for clinical applications such as mammography. PMID:26756405

OECD/NEA expert group on uncertainty analysis for criticality safety assessment: Results of benchmark on sensitivity calculation (phase III)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ivanova, T.; Laville, C.; Dyrda, J.

2012-07-01

The sensitivities of the k{sub eff} eigenvalue to neutron cross sections have become commonly used in similarity studies and as part of the validation algorithm for criticality safety assessments. To test calculations of the sensitivity coefficients, a benchmark study (Phase III) has been established by the OECD-NEA/WPNCS/EG UACSA (Expert Group on Uncertainty Analysis for Criticality Safety Assessment). This paper presents some sensitivity results generated by the benchmark participants using various computational tools based upon different computational methods: SCALE/TSUNAMI-3D and -1D, MONK, APOLLO2-MORET 5, DRAGON-SUSD3D and MMKKENO. The study demonstrates the performance of the tools. It also illustrates how model simplificationsmore » impact the sensitivity results and demonstrates the importance of 'implicit' (self-shielding) sensitivities. This work has been a useful step towards verification of the existing and developed sensitivity analysis methods. (authors)« less

Tunable wavefront coded imaging system based on detachable phase mask: Mathematical analysis, optimization and underlying applications

NASA Astrophysics Data System (ADS)

Zhao, Hui; Wei, Jingxuan

2014-09-01

The key to the concept of tunable wavefront coding lies in detachable phase masks. Ojeda-Castaneda et al. (Progress in Electronics Research Symposium Proceedings, Cambridge, USA, July 5-8, 2010) described a typical design in which two components with cosinusoidal phase variation operate together to make defocus sensitivity tunable. The present study proposes an improved design and makes three contributions: (1) A mathematical derivation based on the stationary phase method explains why the detachable phase mask of Ojeda-Castaneda et al. tunes the defocus sensitivity. (2) The mathematical derivations show that the effective bandwidth wavefront coded imaging system is also tunable by making each component of the detachable phase mask move asymmetrically. An improved Fisher information-based optimization procedure was also designed to ascertain the optimal mask parameters corresponding to specific bandwidth. (3) Possible applications of the tunable bandwidth are demonstrated by simulated imaging.

Circadian Periods of Sensitivity for Ramelteon on the onset of Running-wheel Activity and the Peak of Suprachiasmatic Nucleus Neuronal Firing Rhythms in C3H/HeN Mice

PubMed Central

Rawashdeh, Oliver; Hudson, Randall L.; Stepien, Iwona; Dubocovich, Margarita L.

2016-01-01

Ramelteon, an MT1/MT2 melatonin receptor agonist, is used for the treatment of sleep-onset insomnia and circadian sleep disorders. Ramelteon phase shifts circadian rhythms in rodents and humans when given at the end of the subjective day; however, its efficacy at other circadian times is not known. Here, the authors determined in C3H/ HeN mice the maximal circadian sensitivity for ramelteon in vivo on the onset of circadian running-wheel activity rhythms, and in vitro on the peak of circadian rhythm of neuronal firing in suprachiasmatic nucleus (SCN) brain slices. The phase response curve (PRC) for ramelteon (90 μg/mouse, subcutaneous [sc]) on circadian wheel-activity rhythms shows maximal sensitivity during the late mid to end of the subjective day, between CT8 and CT12 (phase advance), and late subjective night and early subjective day, between CT20 and CT2 (phase delay), using a 3-day-pulse treatment regimen in C3H/HeN mice. The PRC for ramelteon resembles that for melatonin in C3H/ HeN mice, showing the same magnitude of maximal shifts at CT10 and CT2, except that the range of sensitivity for ramelteon (CT8–CT12) during the subjective day is broader. Furthermore, in SCN brain slices in vitro, ramelteon (10 pM) administered at CT10 phase advances (5.6 ± 0.29 h, n = 3) and at CT2 phase delays (−3.2 ± 0.12 h, n = 6) the peak of circadian rhythm of neuronal firing, with the shifts being significantly larger than those induced by melatonin (10 pM) at the same circadian times (CT10: 2.7 ± 0.15 h, n = 4, p < .05; CT2: −1.13 ± 0.08 h, n = 6, p < .001, respectively). The phase shifts induced by both melatonin and ramelteon in the SCN brain slice at either CT10 or CT2 corresponded with the period of sensitivity observed in vivo. In conclusion, melatonin and ramelteon showed identical periods of circadian sensitivity at CT10 (advance) and CT2 (delay) to shift the onset of circadian activity rhythms in vivo and the peak of SCN neuronal firing rhythms in vitro. PMID:21182402

The effects of display time and eccentricity on the detection of amplitude and phase degradations in textured stimuli.

PubMed

Clarke, Alasdair D F; Green, Patrick R; Chantler, Mike J

2012-03-08

The amplitude and phase spectra of an image contain important information for perception, and a large body of work has investigated the effects of manipulating these spectra on the recognition or classification of image content. Here, we use a novel means of investigating sensitivity to amplitude and phase spectra properties, testing the ability of observers to detect degradations of the spectral content of synthetic images of textured surfaces that are broadband in the frequency domain. The effects of display time and retinal eccentricity on sensitivity to these two manipulations are compared using stimuli matched for difficulty of detection. We find no difference between the time courses for the detection of degradation in the two spectra; in both cases, accuracy rises above chance when display times are greater than 80 ms. Increasing retinal eccentricity to 8.7°, however, has a significantly stronger effect on the accuracy of detecting degradations of the amplitude spectrum than of the phase spectrum. Further, sensitivity to phase randomization that is restricted to low spatial frequencies is greater in the periphery (at 8.7° eccentricity) than in the fovea. These last two results imply that the fovea and periphery are specialized for the processing of phase spectrum information in distinct spatial frequency bands.

Experimental implementation of phase locking in a nonlinear interferometer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Hailong; Jing, Jietai, E-mail: jtjing@phy.ecnu.edu.cn; Marino, A. M.

2015-09-21

Based upon two cascade four-wave mixing processes in two identical hot rubidium vapor cells, a nonlinear interferometer has been experimentally realized [Jing et al., Appl. Phys. Lett. 99, 011110 (2011); Hudelist et al., Nat. Commun. 5, 3049 (2014)]. It has a higher degree of phase sensitivity than a traditional linear interferometer and has many potential applications in quantum metrology. Phase locking of the nonlinear interferometer is needed before it can find its way into applications. In this letter, we investigate the experimental implementation of phase locking of the relative phase between the three beams at different frequencies involved in suchmore » a nonlinear interferometer. We have utilized two different methods, namely, beat note locking and coherent modulation locking. We find that coherent modulation locking can achieve much better phase stability than beat note locking in our system. Our results pave the way for real applications of a nonlinear interferometer in precision measurement and quantum manipulation, for example, phase control in phase-sensitive N-wave mixing process, N-port nonlinear interferometer and quantum-enhanced real-time phase tracking.« less

Inferior colliculus contributions to phase encoding of stop consonants in an animal model

PubMed Central

Warrier, Catherine M; Abrams, Daniel A; Nicol, Trent G; Kraus, Nina

2011-01-01

The human auditory brainstem is known to be exquisitely sensitive to fine-grained spectro-temporal differences between speech sound contrasts, and the ability of the brainstem to discriminate between these contrasts is important for speech perception. Recent work has described a novel method for translating brainstem timing differences in response to speech contrasts into frequency-specific phase differentials. Results from this method have shown that the human brainstem response is surprisingly sensitive to phase-differences inherent to the stimuli across a wide extent of the spectrum. Here we use an animal model of the auditory brainstem to examine whether the stimulus-specific phase signatures measured in human brainstem responses represent an epiphenomenon associated with far field (i.e., scalp-recorded) measurement of neural activity, or alternatively whether these specific activity patterns are also evident in auditory nuclei that contribute to the scalp-recorded response, thereby representing a more fundamental temporal processing phenomenon. Responses in anaesthetized guinea pigs to three minimally-contrasting consonant-vowel stimuli were collected simultaneously from the cortical surface vertex and directly from central nucleus of the inferior colliculus (ICc), measuring volume conducted neural activity and multiunit, near-field activity, respectively. Guinea pig surface responses were similar to human scalp-recorded responses to identical stimuli in gross morphology as well as phase characteristics. Moreover, surface recorded potentials shared many phase characteristics with near-field ICc activity. Response phase differences were prominent during formant transition periods, reflecting spectro-temporal differences between syllables, and showed more subtle differences during the identical steady-state periods. ICc encoded stimulus distinctions over a broader frequency range, with differences apparent in the highest frequency ranges analyzed, up to 3000 Hz. Based on the similarity of phase encoding across sites, and the consistency and sensitivity of response phase measured within ICc, results suggest that a general property of the auditory system is a high degree of sensitivity to fine-grained phase information inherent to complex acoustical stimuli. Furthermore, results suggest that temporal encoding in ICc contributes to temporal features measured in speech-evoked scalp-recorded responses. PMID:21945200

High sensitivity liquid phase measurements using broadband cavity enhanced absorption spectroscopy (BBCEAS) featuring a low cost webcam based prism spectrometer.

PubMed

Qu, Zhechao; Engstrom, Julia; Wong, Donald; Islam, Meez; Kaminski, Clemens F

2013-11-07

Cavity enhanced techniques enable high sensitivity absorption measurements in the liquid phase but are typically more complex, and much more expensive, to perform than conventional absorption methods. The latter attributes have so far prevented a wide spread use of these methods in the analytical sciences. In this study we demonstrate a novel BBCEAS instrument that is sensitive, yet simple and economical to set up and operate. We use a prism spectrometer with a low cost webcam as the detector in conjunction with an optical cavity consisting of two R = 0.99 dielectric mirrors and a white light LED source for illumination. High sensitivity liquid phase measurements were made on samples contained in 1 cm quartz cuvettes placed at normal incidence to the light beam in the optical cavity. The cavity enhancement factor (CEF) with water as the solvent was determined directly by phase shift cavity ring down spectroscopy (PS-CRDS) and also by calibration with Rhodamine 6G solutions. Both methods yielded closely matching CEF values of ~60. The minimum detectable change in absorption (αmin) was determined to be 6.5 × 10(-5) cm(-1) at 527 nm and was limited only by the 8 bit resolution of the particular webcam detector used, thus offering scope for further improvement. The instrument was used to make representative measurements on dye solutions and in the determination of nitrite concentrations in a variation of the widely used Griess Assay. Limits of detection (LOD) were ~850 pM for Rhodamine 6G and 3.7 nM for nitrite, respectively. The sensitivity of the instrument compares favourably with previous cavity based liquid phase studies whilst being achieved at a small fraction of the cost hitherto reported, thus opening the door to widespread use in the community. Further means of improving sensitivity are discussed in the paper.

Phase-sensitive imaging of the outer retina using optical coherence tomography and adaptive optics

PubMed Central

Jonnal, Ravi S.; Kocaoglu, Omer P.; Wang, Qiang; Lee, Sangyeol; Miller, Donald T.

2011-01-01

The cone photoreceptor’s outer segment (OS) experiences changes in optical path length, both in response to visible stimuli and as a matter of its daily course of renewal and shedding. These changes are of interest, to quantify function in healthy cells and assess dysfunction in diseased ones. While optical coherence tomography (OCT), combined with adaptive optics (AO), has permitted unprecedented three-dimensional resolution in the living retina, it has not generally been able to measure these OS dynamics, whose scale is smaller than OCT’s axial resolution of a few microns. A possible solution is to take advantage of the phase information encoded in the OCT signal. Phase-sensitive implementations of spectral-domain optical coherence tomography (SD-OCT) have been demonstrated, capable of resolving sample axial displacements much smaller than the imaging wavelength, but these have been limited to ex vivo samples. In this paper we present a novel technique for retrieving phase information from OCT volumes of the outer retina. The key component of our technique is quantification of phase differences within the retina. We provide a quantitative analysis of such phase information and show that–when combined with appropriate methods for filtering and unwrapping–it can improve the sensitivity to OS length change by more than an order of magnitude, down to 45 nm, slightly thicker than a single OS disc. We further show that phase sensitivity drops off with retinal eccentricity, and that the best location for phase imaging is close to the fovea. We apply the technique to the measurement of sub-resolution changes in the OS over matters of hours. Using custom software for registration and tracking, these microscopic changes are monitored in hundreds of cones over time. In two subjects, the OS was found to have average elongation rates of 150 nm/hr, values which agree with our previous findings. PMID:22254172

Cutaneous irritancy of an ibuprofen medicated plaster in healthy volunteers.

PubMed

Maganji, Manisha; Connolly, Mark P; Bhatt, Aomesh

2018-04-01

To assess the irritation and contact sensitization potential of a 200 mg ibuprofen medicated plaster. This double-blind, phase-1 placebo controlled study had two phases; the induction phase to evaluate the irritant potential of continuous application of the plaster, and the challenge phase to assess contact sensitivity (allergy). The cumulative irritancy potential was evaluated using an adaptation of the Shelanski method. Healthy adults (≥18 years of age) (N = 210) were treated simultaneously with one ibuprofen medicated and one placebo plaster applied in a randomized fashion to either the left or right side of the lower back. During the induction phase, plasters were applied on Days 1, 3, 5, 8, 10, 12, 15, 17, and 19 and the final plaster removed on Day 22. At each scheduled visit plasters and applications sites were assessed for degree of adhesion and skin irritation (score of 1 = no irritation to 7 = strong reaction spreading beyond test sites), respectively. The challenge phase followed a two-week washout period. A plaster was applied on Day 36 for 48 h and assessment occurred on Days 38, 39, and 40. The mean cumulative irritation score during the induction phase was lower for the ibuprofen medicated plaster than the placebo plaster (0.32 vs. 1.23, respectively). Three (1.4%) subjects experience a dermal reaction of grade ≥3 for the ibuprofen medicated plaster compared with 27 (12.7%) for the placebo plaster. Following challenge with ibuprofen or placebo plasters, 12 subjects (6.2%) with the ibuprofen medicated plaster and four (2.2%) with the placebo plaster had skin reaction of assessment grade higher than the induction phase. One subject for the ibuprofen and two for the placebo plaster had reactions with grade >2. No subjects showed an increase in sensitization on Day 39 or 40 compared with Day 38. The findings indicate that the both the irritancy and contact sensitization of the ibuprofen medicated plaster is acceptable.

Status of the MARE experiment in Milan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ferri, E.; Arnaboldi, C.; Ceruti, G.

2009-12-16

An international collaboration has grown around the project of Microcalorimeter Arrays for a Rhenium Experiment (MARE) for a direct and calorimetric measurement of the electron antineutrino mass with sub-electronvolt sensitivity.MARE is divided into two phases. The first phase (MARE-1) consists of two independent experiments using the presently available detector technology to reach a sensitivity of m{sub v}{<=}2eV/c{sup 2}. The goal of the second phase (MARE-2) is to achieve a sub-electronvolt sensitivity on the neutrino mass.The Milan MARE-1 experiment is based on arrays of silicon implanted microcalorimeters, produced by NASA/GSFC, with dielectric silver perrhenate absorbers, AgReO{sub 4}. We present here themore » status of MARE-1 in Milan which is starting data taking with 2 arrays (72 detectors). In this configuration a sensitivity of about 5 eV can be achieved in two years. We describe in details the experimental setup which is designed to host up to 8 arrays (288 detectors). With 8 arrays, two years of measurement would improve the sensitivity to about 3 eV. This talk reports on the activity of the group for the MARE project in Milan.« less

Monte-Carlo-based phase retardation estimator for polarization sensitive optical coherence tomography

NASA Astrophysics Data System (ADS)

Duan, Lian; Makita, Shuichi; Yamanari, Masahiro; Lim, Yiheng; Yasuno, Yoshiaki

2011-08-01

A Monte-Carlo-based phase retardation estimator is developed to correct the systematic error in phase retardation measurement by polarization sensitive optical coherence tomography (PS-OCT). Recent research has revealed that the phase retardation measured by PS-OCT has a distribution that is neither symmetric nor centered at the true value. Hence, a standard mean estimator gives us erroneous estimations of phase retardation, and it degrades the performance of PS-OCT for quantitative assessment. In this paper, the noise property in phase retardation is investigated in detail by Monte-Carlo simulation and experiments. A distribution transform function is designed to eliminate the systematic error by using the result of the Monte-Carlo simulation. This distribution transformation is followed by a mean estimator. This process provides a significantly better estimation of phase retardation than a standard mean estimator. This method is validated both by numerical simulations and experiments. The application of this method to in vitro and in vivo biological samples is also demonstrated.

Quantum-Limited Directional Amplifiers with Optomechanics

NASA Astrophysics Data System (ADS)

Malz, Daniel; Tóth, László D.; Bernier, Nathan R.; Feofanov, Alexey K.; Kippenberg, Tobias J.; Nunnenkamp, Andreas

2018-01-01

Directional amplifiers are an important resource in quantum-information processing, as they protect sensitive quantum systems from excess noise. Here, we propose an implementation of phase-preserving and phase-sensitive directional amplifiers for microwave signals in an electromechanical setup comprising two microwave cavities and two mechanical resonators. We show that both can reach their respective quantum limits on added noise. In the reverse direction, they emit thermal noise stemming from the mechanical resonators; we discuss how this noise can be suppressed, a crucial aspect for technological applications. The isolation bandwidth in both is of the order of the mechanical linewidth divided by the amplitude gain. We derive the bandwidth and gain-bandwidth product for both and find that the phase-sensitive amplifier has an unlimited gain-bandwidth product. Our study represents an important step toward flexible, on-chip integrated nonreciprocal amplifiers of microwave signals.

Loss resilience for two-qubit state transmission using distributed phase sensitive amplification

DOE PAGES

Dailey, James; Agarwal, Anjali; Toliver, Paul; ...

2015-11-12

We transmit phase-encoded non-orthogonal quantum states through a 5-km long fibre-based distributed optical phase-sensitive amplifier (OPSA) using telecom-wavelength photonic qubit pairs. The gain is set to equal the transmission loss to probabilistically preserve input states during transmission. While neither state is optimally aligned to the OPSA, each input state is equally amplified with no measurable degradation in state quality. These results promise a new approach to reduce the effects of loss by encoding quantum information in a two-qubit Hilbert space which is designed to benefit from transmission through an OPSA.

Frequency-degenerate phase-sensitive optical parametric amplification based on four-wave mixing in graphene–silicon slot waveguide

NASA Astrophysics Data System (ADS)

Li, Zhen; Liu, Hongjun; Huang, Nan; Wang, Zhaolu; Han, Jing

2018-06-01

The phase-sensitive amplification process of a hybrid graphene–silicon (HyGS) slot waveguide with trilayers of graphene is investigated in this paper. Numerical simulation shows that a relatively high extinction ratio (42 dB) is achieved, because of the ultrahigh nonlinear coefficients, with a waveguide length of only 680 µm. In addition, the graphene layer provides the possibility of modulating the phase status and gain of the output signal. This study is expected to be highly beneficial to applications such as integrated optics and graphene-related active optical devices.

Loss resilience for two-qubit state transmission using distributed phase sensitive amplification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dailey, James; Agarwal, Anjali; Toliver, Paul

We transmit phase-encoded non-orthogonal quantum states through a 5-km long fibre-based distributed optical phase-sensitive amplifier (OPSA) using telecom-wavelength photonic qubit pairs. The gain is set to equal the transmission loss to probabilistically preserve input states during transmission. While neither state is optimally aligned to the OPSA, each input state is equally amplified with no measurable degradation in state quality. These results promise a new approach to reduce the effects of loss by encoding quantum information in a two-qubit Hilbert space which is designed to benefit from transmission through an OPSA.

Performance Sensitivity Studies on the PIAA Implementation of the High-Contrast Imaging Testbed

NASA Technical Reports Server (NTRS)

Sidick, Erkin; Lou, John; Shaklan, Stuart; Levine, Marie

2010-01-01

This slide presentation reviews the sensitivity studies on the Phase-Induced Amplitude Apodization (PIAA), or pupil mapping using the High-Contrast Imaging Testbed (HCIT). PIAA is a promising technique in high-dynamic range stellar coronagraph. This presentation reports on the investigation of the effects of the phase and rigid-body errors of various optics on the narrowband contrast performance of the PIAA/HCIT hybrid system. The results have shown that the 2-step wavefront control method utilizing 2-DMs is quite effective in compensating the effects of realistic phase and rigid-body errors of various optics

On-chip optical transduction scheme for graphene nano-electro-mechanical systems in silicon-photonic platform.

PubMed

Dash, Aneesh; Selvaraja, S K; Naik, A K

2018-02-15

We present a scheme for on-chip optical transduction of strain and displacement of graphene-based nano-electro-mechanical systems (NEMS). A detailed numerical study on the feasibility of three silicon-photonic integrated circuit configurations is presented: the Mach-Zehnder interferometer (MZI), the micro-ring resonator, and the ring-loaded MZI. An index sensing based technique using an MZI loaded with a ring resonator with a moderate Q-factor of 2400 can yield a sensitivity of 28  fm/Hz and 6.5×10 -6 %/Hz for displacement and strain, respectively. Though any phase-sensitive integrated-photonic device could be used for optical transduction, here we show that optimal sensitivity is achievable by combining resonance with phase sensitivity.

On-chip optical transduction scheme for graphene nano-electro-mechanical systems in silicon-photonic platform

NASA Astrophysics Data System (ADS)

Dash, Aneesh; Selvaraja, S. K.; Naik, A. K.

2018-02-01

We present a scheme for on-chip optical transduction of strain and displacement of Graphene-based Nano-Electro-Mechanical Systems (NEMS). A detailed numerical study on the feasibility of three silicon-photonic integrated circuit configurations is presented: Mach-Zehnder Interferometer(MZI), micro-ring resonator and ring-loaded MZI. An index-sensing based technique using a Mach-Zehnder Interferometer loaded with a ring resonator with a moderate Q-factor of 2400 can yield a sensitivity of 28 fm/sqrt(Hz), and 6.5E-6 %/sqrt(Hz) for displacement and strain respectively. Though any phase sensitive integrated photonic device could be used for optical transduction, here we show that optimal sensitivity is achievable by combining resonance with phase sensitivity.

Single phase computed tomography is equivalent to dual phase method for localizing hyperfunctioning parathyroid glands in patients with primary hyperparathyroidism: a retrospective review

PubMed Central

Morón, Fanny; Delumpa, Alfred; Guffey, Danielle; Dunaway, David

2017-01-01

Objective This study aims to compare the sensitivity of dual phase (non-contrast and arterial) versus single phase (arterial) CT for detection of hyper-functioning parathyroid glands in patients with primary hyperparathyroidism. Methods The CT scans of thirty-two patients who have biochemical evidence of primary hyperparathyroidism, pathologically proven parathyroid adenomas, and pre-operative multiphase parathyroid imaging were evaluated retrospectively in order to compare the adequacy of single phase vs. dual phase CT scans for the detection of parathyroid adenomas. Results The parathyroid adenomas were localized in 83% of cases on single arterial phase CT and 80% of cases on dual phase CT. The specificity for localization of parathyroid tumor was 96% for single phase CT and 97% for dual phase CT. The results were not significantly different (p = 0.695). These results are similar to those found in the literature for multiphase CT of 55–94%. Conclusions Our study supports the use of a single arterial phase CT for the detection of hyperfunctioning parathyroid adenomas. Advances in knowledge: a single arterial phase CT has similar sensitivity for localizing parathyroid adenomas as dual phase CT and significantly reduces radiation dose to the patient. PMID:28828238

Quantitative phase-digital holographic microscopy: a new imaging modality to identify original cellular biomarkers of diseases

NASA Astrophysics Data System (ADS)

Marquet, P.; Rothenfusser, K.; Rappaz, B.; Depeursinge, C.; Jourdain, P.; Magistretti, P. J.

2016-03-01

Quantitative phase microscopy (QPM) has recently emerged as a powerful label-free technique in the field of living cell imaging allowing to non-invasively measure with a nanometric axial sensitivity cell structure and dynamics. Since the phase retardation of a light wave when transmitted through the observed cells, namely the quantitative phase signal (QPS), is sensitive to both cellular thickness and intracellular refractive index related to the cellular content, its accurate analysis allows to derive various cell parameters and monitor specific cell processes, which are very likely to identify new cell biomarkers. Specifically, quantitative phase-digital holographic microscopy (QP-DHM), thanks to its numerical flexibility facilitating parallelization and automation processes, represents an appealing imaging modality to both identify original cellular biomarkers of diseases as well to explore the underlying pathophysiological processes.

Er:Yb phosphate glass laser with nonlinear absorber for phase-sensitive optical time domain reflectometry

NASA Astrophysics Data System (ADS)

Zhirnov, A. A.; Pnev, A. B.; Svelto, C.; Norgia, M.; Pesatori, A.; Galzerano, G.; Laporta, P.; Shelestov, D. A.; Karasik, V. E.

2017-11-01

A novel laser for phase-sensitive optical time-domain reflectometry (Φ-OTDR) is presented. The advantages of a compact solid-state laser are listed, current problems are shown. Experiments with a microchip single-optical-element laser, from setup construction to usage in Φ-OTDR system, are presented. New laser scheme with two-photon intracavity absorber is suggested and its advantages are described.

Using Environment-Sensitive Fluorescent Probes to Characterize Liquid-Liquid Phase Separation in Supersaturated Solutions of Poorly Water Soluble Compounds.

PubMed

Raina, Shweta A; Alonzo, David E; Zhang, Geoff G Z; Gao, Yi; Taylor, Lynne S

2015-11-01

Highly supersaturated aqueous solutions of poorly soluble compounds can undergo liquid-liquid phase separation (LLPS) when the concentration exceeds the "amorphous solubility". This phenomenon has been widely observed during high throughput screening of new molecular entities as well as during the dissolution of amorphous solid dispersions. In this study, we have evaluated the use of environment-sensitive fluorescence probes to investigate the formation and properties of the non-crystalline drug-rich aggregates formed in aqueous solutions as a result of LLPS. Six different environment-sensitive fluorophores were employed to study LLPS in highly supersaturated solutions of several model compounds, all dihydropyridine derivatives. Each fluoroprobe exhibited a large hypsochromic shift with decreasing environment polarity. Upon drug aggregate formation, the probes partitioned into the drug-rich phase and exhibited changes in emission wavelength and intensity consistent with sensing a lower polarity environment. The LLPS onset concentrations determined using the fluorescence measurements were in good agreement with light scattering measurements as well as theoretically estimated amorphous solubility values. Environment-sensitive fluorescence probes are useful to help understand the phase behavior of highly supersaturated aqueous solutions, which in turn is important in the context of developing enabling formulations for poorly soluble compounds.

Bandwidth controller for phase-locked-loop

NASA Technical Reports Server (NTRS)

Brockman, Milton H. (Inventor)

1992-01-01

A phase locked loop utilizing digital techniques to control the closed loop bandwidth of the RF carrier phase locked loop in a receiver provides high sensitivity and a wide dynamic range for signal reception. After analog to digital conversion, a digital phase locked loop bandwidth controller provides phase error detection with automatic RF carrier closed loop tracking bandwidth control to accommodate several modes of transmission.

Brain metabolic pattern analysis using a magnetic resonance spectra classification software in experimental stroke.

PubMed

Jiménez-Xarrié, Elena; Davila, Myriam; Candiota, Ana Paula; Delgado-Mederos, Raquel; Ortega-Martorell, Sandra; Julià-Sapé, Margarida; Arús, Carles; Martí-Fàbregas, Joan

2017-01-13

Magnetic resonance spectroscopy (MRS) provides non-invasive information about the metabolic pattern of the brain parenchyma in vivo. The SpectraClassifier software performs MRS pattern-recognition by determining the spectral features (metabolites) which can be used objectively to classify spectra. Our aim was to develop an Infarct Evolution Classifier and a Brain Regions Classifier in a rat model of focal ischemic stroke using SpectraClassifier. A total of 164 single-voxel proton spectra obtained with a 7 Tesla magnet at an echo time of 12 ms from non-infarcted parenchyma, subventricular zones and infarcted parenchyma were analyzed with SpectraClassifier ( http://gabrmn.uab.es/?q=sc ). The spectra corresponded to Sprague-Dawley rats (healthy rats, n = 7) and stroke rats at day 1 post-stroke (acute phase, n = 6 rats) and at days 7 ± 1 post-stroke (subacute phase, n = 14). In the Infarct Evolution Classifier, spectral features contributed by lactate + mobile lipids (1.33 ppm), total creatine (3.05 ppm) and mobile lipids (0.85 ppm) distinguished among non-infarcted parenchyma (100% sensitivity and 100% specificity), acute phase of infarct (100% sensitivity and 95% specificity) and subacute phase of infarct (78% sensitivity and 100% specificity). In the Brain Regions Classifier, spectral features contributed by myoinositol (3.62 ppm) and total creatine (3.04/3.05 ppm) distinguished among infarcted parenchyma (100% sensitivity and 98% specificity), non-infarcted parenchyma (84% sensitivity and 84% specificity) and subventricular zones (76% sensitivity and 93% specificity). SpectraClassifier identified candidate biomarkers for infarct evolution (mobile lipids accumulation) and different brain regions (myoinositol content).

Learning in the Absence of Experience-Dependent Regulation of NMDAR Composition

ERIC Educational Resources Information Center

Lebel, David; Sidhu, Nishchal; Barkai, Edi; Quinlan, Elizabeth M.

2006-01-01

Olfactory discrimination (OD) learning consists of two phases: an initial N-methyl-d-aspartate (NMDA) receptor--sensitive rule-learning phase, followed by an NMDA receptor (NMDAR)--insensitive pair-learning phase. The rule-learning phase is accompanied by changes in the composition and function of NMDARs at synapses in the piriform cortex,…

Simulations of arctic mixed-phase clouds in forecasts with CAM3 and AM2 for M-PACE

DOE PAGES

Xie, Shaocheng; Boyle, James; Klein, Stephen A.; ...

2008-02-27

[1] Simulations of mixed-phase clouds in forecasts with the NCAR Atmosphere Model version 3 (CAM3) and the GFDL Atmospheric Model version 2 (AM2) for the Mixed-Phase Arctic Cloud Experiment (M-PACE) are performed using analysis data from numerical weather prediction centers. CAM3 significantly underestimates the observed boundary layer mixed-phase cloud fraction and cannot realistically simulate the variations of liquid water fraction with temperature and cloud height due to its oversimplified cloud microphysical scheme. In contrast, AM2 reasonably reproduces the observed boundary layer cloud fraction while its clouds contain much less cloud condensate than CAM3 and the observations. The simulation of themore » boundary layer mixed-phase clouds and their microphysical properties is considerably improved in CAM3 when a new physically based cloud microphysical scheme is used (CAM3LIU). The new scheme also leads to an improved simulation of the surface and top of the atmosphere longwave radiative fluxes. Sensitivity tests show that these results are not sensitive to the analysis data used for model initialization. Increasing model horizontal resolution helps capture the subgrid-scale features in Arctic frontal clouds but does not help improve the simulation of the single-layer boundary layer clouds. AM2 simulated cloud fraction and LWP are sensitive to the change in cloud ice number concentrations used in the Wegener-Bergeron-Findeisen process while CAM3LIU only shows moderate sensitivity in its cloud fields to this change. Furthermore, this paper shows that the Wegener-Bergeron-Findeisen process is important for these models to correctly simulate the observed features of mixed-phase clouds.« less

Simulations of Arctic mixed-phase clouds in forecasts with CAM3 and AM2 for M-PACE

NASA Astrophysics Data System (ADS)

Xie, Shaocheng; Boyle, James; Klein, Stephen A.; Liu, Xiaohong; Ghan, Steven

2008-02-01

Simulations of mixed-phase clouds in forecasts with the NCAR Atmosphere Model version 3 (CAM3) and the GFDL Atmospheric Model version 2 (AM2) for the Mixed-Phase Arctic Cloud Experiment (M-PACE) are performed using analysis data from numerical weather prediction centers. CAM3 significantly underestimates the observed boundary layer mixed-phase cloud fraction and cannot realistically simulate the variations of liquid water fraction with temperature and cloud height due to its oversimplified cloud microphysical scheme. In contrast, AM2 reasonably reproduces the observed boundary layer cloud fraction while its clouds contain much less cloud condensate than CAM3 and the observations. The simulation of the boundary layer mixed-phase clouds and their microphysical properties is considerably improved in CAM3 when a new physically based cloud microphysical scheme is used (CAM3LIU). The new scheme also leads to an improved simulation of the surface and top of the atmosphere longwave radiative fluxes. Sensitivity tests show that these results are not sensitive to the analysis data used for model initialization. Increasing model horizontal resolution helps capture the subgrid-scale features in Arctic frontal clouds but does not help improve the simulation of the single-layer boundary layer clouds. AM2 simulated cloud fraction and LWP are sensitive to the change in cloud ice number concentrations used in the Wegener-Bergeron-Findeisen process while CAM3LIU only shows moderate sensitivity in its cloud fields to this change. This paper shows that the Wegener-Bergeron-Findeisen process is important for these models to correctly simulate the observed features of mixed-phase clouds.

Utility of contrast-enhanced computed tomography in the evaluation of canine insulinoma location.

PubMed

Buishand, Floryne O; Vilaplana Grosso, Federico R; Kirpensteijn, Jolle; van Nimwegen, Sebastiaan A

2018-06-05

To determine 1) the sensitivity of contrast-enhanced CT (CECT) for detection of primary canine insulinomas and metastases 2) the sensitivity of CECT to locate canine insulinomas within the pancreas and 3) the CECT attenuation pattern of canine insulinomas and post-contrast phase in which insulinomas have the best visibility. A retrospective review was performed of the medical records of 27 canine insulinoma patients. Simultaneous occurrence of blood glucose < 3.5 mmol/L (reference interval: 4.2-5.8 mmol/L) and plasma insulin > 10 mIU/L (reference interval: 1.4-24.5 mIU/L) were considered diagnostic for insulinoma. The dogs had a mean age of 9.0 ± 1.7 (SD) years and comprised 11 males and 17 females. Using CECT-scans, 26/27 insulinomas were successfully detected. However, CECT-scans predicted the correct location of insulinomas within the pancreas in only 14/27 dogs. In 9/13 inaccurately located insulinoma cases, the location error was major. There was no significant difference between triple, double and single-phase CECT-scans with location accuracies of 54%, 50% and 50%, respectively. Also, there was no specific post-contrast phase in which insulinomas could be visualised best. Detection of lymph node metastases with CECT-scans had a sensitivity of 67% (10/15 lymph node metastases). Detection of liver metastases had a sensitivity of 75% (6/8 liver metastases). This study highlights that major location errors mainly occurred if single- or double-phase CECT-scans were used (6/9 cases). It is suggested that triple-phase CECT-scans have superior outcome over single- or double-phase CECT-scans in pre-operative imaging of canine insulinomas.

A single bout of exhaustive exercise affects integrated baroreflex function after 16 days of head-down tilt

NASA Technical Reports Server (NTRS)

Engelke, K. A.; Doerr, D. F.; Convertino, V. A.

1995-01-01

We tested the hypothesis that one bout of maximal exercise performed 24 h before reambulation from 16 days of 6 degrees head-down tilt (HDT) could increase integrated baroreflex sensitivity. Isolated carotid-cardiac and integrated baroreflex function was assessed in seven subjects before and after two periods of HDT separated by 11 mo. On the last day of one HDT period, subjects performed a single bout of maximal cycle ergometry (exercise). Subjects did not exercise after the other HDT period (control). Carotid-cardiac baroreflex sensitivity was evaluated using a neck collar device. Integrated baroreflex function was assessed by recording heart rate (HR) and blood pressure (MAP) during a 15-s Valsalva maneuver (VM) at a controlled expiratory pressure of 30 mmHg. The ratio of change in HR to change in MAP (delta HR/ delta MAP) during phases II and IV of the VM was used as an index of cardiac baroreflex sensitivity. Baroreflex-mediated vasoconstriction was assessed by measuring the late phase II rise in MAP. Following HDT, carotid-cardiac baroreflex sensitivity was reduced (2.8 to 2.0 ms/mmHg; P = 0.05) as was delta HR/ delta MAP during phase II (-1.5 to -0.8 beats/mmHg; P = 0.002). After exercise, isolated carotid baroreflex activity and phase II delta HR/ delta MAP returned to pre-HDT levels but remained attenuated in the control condition. Phase IV delta HR/ delta MAP was not altered by HDT or exercise. The late phase II increase of MAP was 71% greater after exercise compared with control (7 vs. 2 mmHg; P = 0.041).(ABSTRACT TRUNCATED AT 250 WORDS).

Women with premenstrual dysphoric disorder have altered sensitivity to allopregnanolone over the menstrual cycle compared to controls-a pilot study.

PubMed

Timby, Erika; Bäckström, Torbjörn; Nyberg, Sigrid; Stenlund, Hans; Wihlbäck, Anna-Carin N; Bixo, Marie

2016-06-01

In premenstrual dysphoric disorder (PMDD), a condition that afflicts 3-8 % of women in fertile ages, the cyclic recurrence of debilitating mood symptoms is restricted to the luteal phase of the menstrual cycle. The progesterone metabolite allopregnanolone is produced by the corpus luteum, and circulating levels are reflected in the brain. Allopregnanolone is a modulator of the GABAA receptor, enhancing the effect of γ-aminobutyric acid (GABA). Previous studies have demonstrated different sensitivity to other GABAA receptor agonists, i.e., benzodiazepines, alcohol, and pregnanolone, in PMDD patients compared to controls. This study aimed to investigate the sensitivity to intravenous allopregnanolone over the menstrual cycle in PMDD patients. Allopregnanolone, 0.05 mg/kg, was administered intravenously once in the mid-follicular and once in the luteal phase of the menstrual cycle to 10 PMDD patients and 10 control subjects. The saccadic eye velocity (SEV) was recorded by electrooculography as a measurement of functional GABAA receptor activity, at baseline and repeatedly after the injection. A mixed model was used to analyze data. There was a highly significant group × phase interaction in the SEV response to allopregnanolone (F(1,327.489) = 12.747, p < 0.001). In the PMDD group, the SEV response was decreased in the follicular phase compared to the luteal phase (F(1,168) = 7.776, p = 0.006), whereas in the control group, the difference was opposite during the menstrual cycle (F(1,158.45) = 5.70, p = 0.018). The effect of exogenous allopregnanolone is associated with menstrual cycle phase in PMDD patients and in controls. The results suggest an altered sensitivity to allopregnanolone in PMDD patients.

Comparative Sensitivities of Gravitational Wave Detectors Based on Atom Interferometers and Light Interferometers

NASA Technical Reports Server (NTRS)

Baker, John G.; Thorpe, J. I.

2012-01-01

We consider a class of proposed gravitational wave detectors based on multiple atomic interferometers separated by large baselines and referenced by common laser systems. We compute the sensitivity limits of these detectors due to intrinsic phase noise of the light sources, non-inertial motion of the light sources, and atomic shot noise and compare them to sensitivity limits for traditional light interferometers. We find that atom interferometers and light interferometers are limited in a nearly identical way by intrinsic phase noise and that both require similar mitigation strategies (e.g. multiple arm instruments) to reach interesting sensitivities. The sensitivity limit from motion of the light sources is slightly different and favors the atom interferometers in the low-frequency limit, although the limit in both cases is severe. Whether this potential advantage outweighs the additional complexity associated with including atom interferometers will require further study.

Sensitivity and dose dependency of radiation-induced injury in hematopoietic stem/progenitor cells in mice

PubMed Central

Guo, Chang-Ying; Luo, Lan; Urata, Yoshishige; Goto, Shinji; Huang, Wen-Jing; Takamura, Syu; Hayashi, Fumiko; Doi, Hanako; Kitajima, Yuriko; Ono, Yusuke; Ogi, Tomoo; Li, Tao-Sheng

2015-01-01

We evaluated the sensitivity and dose dependency of radiation-induced injury in hematopoietic stem/progenitor cells. Adult C57BL/6 mice were daily exposed to 0, 2, 10, 50, and 250 mGy γ-ray for 1 month in succession, respectively. The damage of hematopoietic stem/progenitor cells in bone marrow were investigated within 2 hours (acute phase) or at 3 months (chronic phase) after the last exposure. Daily exposure to over 10 mGy γ-ray significantly decreased the number and colony-forming capacity of hematopoietic stem/progenitor cells at acute phase, and did not completely recover at chronic phase with 250 mGy exposure. Interestingly, the daily exposure to 10 or 50 mGy γ-ray decreased the formation of mixed types of colonies at chronic phase, but the total number of colonies was comparable to control. Immunostaining analysis showed that the formation of 53BP1 foci in c-kit+ stem/progenitor cells was significantly increased with daily exposure to 50 and 250 mGy at acute phase, and 250 mGy at chronic phase. Many genes involved in toxicity responses were up- or down-regulated with the exposures to all doses. Our data have clearly shown the sensitivity and dose dependency of radiation-induced injury in hematopoietic stem/progenitor cells of mice with daily exposures to 2 ~ 250 mGy γ-ray. PMID:25623887

Menstrual cycle phase affects discrimination of infant cuteness.

PubMed

Lobmaier, Janek S; Probst, Fabian; Perrett, David I; Heinrichs, Markus

2015-04-01

Recent studies have shown that women are more sensitive than men to subtle cuteness differences in infant faces. It has been suggested that raised levels in estradiol and progesterone may be responsible for this advantage. We compared young women's sensitivity to computer-manipulated baby faces varying in cuteness. Thirty-six women were tested once during ovulation and once during the luteal phase of their menstrual cycle. In a two alternative forced-choice experiment, participants chose the baby which they thought was cuter (Task 1), younger (Task 2), or the baby that they would prefer to babysit (Task 3). Saliva samples to assess levels of estradiol, progesterone and testosterone were collected at each test session. During ovulation, women were more likely to choose the cuter baby than during the luteal phase, in all three tasks. These results suggest that cuteness discrimination may be driven by cyclic hormonal shifts. However none of the measured hormones were related to increased cuteness sensitivity. We speculate that other hormones than the ones measured here might be responsible for the increased sensitivity to subtle cuteness differences during ovulation. Copyright © 2015 Elsevier Inc. All rights reserved.

Optimization of a fiber optic flexible disk microphone

NASA Astrophysics Data System (ADS)

Zhang, Gang; Yu, Benli; Wang, Hui; Liu, Fei; Peng, Jun; Wu, Xuqiang

2011-11-01

An optimized design of a fiber optic flexible disk microphone is presented and verified experimentally. The phase sensitivity of optical fiber microphone (both the ideal model with a simply supported disk (SSD) and the model with a clamped disk (CLD)) is analyzed by utilizing theory of plates and shells. The results show that the microphones have an optimum length of the sensing arm when inner radius of the fiber coils, radius and Poisson's radio of the flexible disk have been determined. Under a typical condition depicted in this paper, an optimum phase sensitivity for SSD model of 27.72 rad/Pa (-91.14 dB re 1 rad/μPa) and an optimum phase sensitivity for CLD model of 3.18 rad/Pa (-109.95 dB re 1 rad/μPa), can be achieved in theory. Several sample microphones are fabricated and tested. The experimental results are basically consistent with the theoretical analysis.

The SNO+ Scintillator Purification Plant and Projected Sensitivity to Solar Neutrinos in the Pure Scintillator Phase

NASA Astrophysics Data System (ADS)

Pershing, Teal; SNO+ Collaboration

2016-03-01

The SNO+ detector is a neutrino and neutrinoless double-beta decay experiment utilizing the renovated SNO detector. In the second phase of operation, the SNO+ detector will contain 780 tons of organic liquid scintillator composed of 2 g/L 2,5-diphenyloxazole (PPO) in linear alkylbenzene (LAB). In this phase, SNO+ will strive to detect solar neutrinos in the sub-MeV range, including CNO production neutrinos and pp production neutrinos. To achieve the necessary detector sensitivity, a four-part scintillator purification plant has been constructed in SNOLAB for the removal of ionic and radioactive impurities. We present an overview of the SNO+ scintillator purification plant stages, including distillation, water extraction, gas stripping, and metal scavenger columns. We also give the projected SNO+ sensitivities to various solar-produced neutrinos based on the scintillator plant's projected purification efficiency.

Analysis of image formation in optical coherence elastography using a multiphysics approach

PubMed Central

Chin, Lixin; Curatolo, Andrea; Kennedy, Brendan F.; Doyle, Barry J.; Munro, Peter R. T.; McLaughlin, Robert A.; Sampson, David D.

2014-01-01

Image formation in optical coherence elastography (OCE) results from a combination of two processes: the mechanical deformation imparted to the sample and the detection of the resulting displacement using optical coherence tomography (OCT). We present a multiphysics model of these processes, validated by simulating strain elastograms acquired using phase-sensitive compression OCE, and demonstrating close correspondence with experimental results. Using the model, we present evidence that the approximation commonly used to infer sample displacement in phase-sensitive OCE is invalidated for smaller deformations than has been previously considered, significantly affecting the measurement precision, as quantified by the displacement sensitivity and the elastogram signal-to-noise ratio. We show how the precision of OCE is affected not only by OCT shot-noise, as is usually considered, but additionally by phase decorrelation due to the sample deformation. This multiphysics model provides a general framework that could be used to compare and contrast different OCE techniques. PMID:25401007

A novel on-line spatial-temporal k-anonymity method for location privacy protection from sequence rules-based inference attacks.

PubMed

Zhang, Haitao; Wu, Chenxue; Chen, Zewei; Liu, Zhao; Zhu, Yunhong

2017-01-01

Analyzing large-scale spatial-temporal k-anonymity datasets recorded in location-based service (LBS) application servers can benefit some LBS applications. However, such analyses can allow adversaries to make inference attacks that cannot be handled by spatial-temporal k-anonymity methods or other methods for protecting sensitive knowledge. In response to this challenge, first we defined a destination location prediction attack model based on privacy-sensitive sequence rules mined from large scale anonymity datasets. Then we proposed a novel on-line spatial-temporal k-anonymity method that can resist such inference attacks. Our anti-attack technique generates new anonymity datasets with awareness of privacy-sensitive sequence rules. The new datasets extend the original sequence database of anonymity datasets to hide the privacy-sensitive rules progressively. The process includes two phases: off-line analysis and on-line application. In the off-line phase, sequence rules are mined from an original sequence database of anonymity datasets, and privacy-sensitive sequence rules are developed by correlating privacy-sensitive spatial regions with spatial grid cells among the sequence rules. In the on-line phase, new anonymity datasets are generated upon LBS requests by adopting specific generalization and avoidance principles to hide the privacy-sensitive sequence rules progressively from the extended sequence anonymity datasets database. We conducted extensive experiments to test the performance of the proposed method, and to explore the influence of the parameter K value. The results demonstrated that our proposed approach is faster and more effective for hiding privacy-sensitive sequence rules in terms of hiding sensitive rules ratios to eliminate inference attacks. Our method also had fewer side effects in terms of generating new sensitive rules ratios than the traditional spatial-temporal k-anonymity method, and had basically the same side effects in terms of non-sensitive rules variation ratios with the traditional spatial-temporal k-anonymity method. Furthermore, we also found the performance variation tendency from the parameter K value, which can help achieve the goal of hiding the maximum number of original sensitive rules while generating a minimum of new sensitive rules and affecting a minimum number of non-sensitive rules.

A novel on-line spatial-temporal k-anonymity method for location privacy protection from sequence rules-based inference attacks

PubMed Central

Wu, Chenxue; Liu, Zhao; Zhu, Yunhong

2017-01-01

Analyzing large-scale spatial-temporal k-anonymity datasets recorded in location-based service (LBS) application servers can benefit some LBS applications. However, such analyses can allow adversaries to make inference attacks that cannot be handled by spatial-temporal k-anonymity methods or other methods for protecting sensitive knowledge. In response to this challenge, first we defined a destination location prediction attack model based on privacy-sensitive sequence rules mined from large scale anonymity datasets. Then we proposed a novel on-line spatial-temporal k-anonymity method that can resist such inference attacks. Our anti-attack technique generates new anonymity datasets with awareness of privacy-sensitive sequence rules. The new datasets extend the original sequence database of anonymity datasets to hide the privacy-sensitive rules progressively. The process includes two phases: off-line analysis and on-line application. In the off-line phase, sequence rules are mined from an original sequence database of anonymity datasets, and privacy-sensitive sequence rules are developed by correlating privacy-sensitive spatial regions with spatial grid cells among the sequence rules. In the on-line phase, new anonymity datasets are generated upon LBS requests by adopting specific generalization and avoidance principles to hide the privacy-sensitive sequence rules progressively from the extended sequence anonymity datasets database. We conducted extensive experiments to test the performance of the proposed method, and to explore the influence of the parameter K value. The results demonstrated that our proposed approach is faster and more effective for hiding privacy-sensitive sequence rules in terms of hiding sensitive rules ratios to eliminate inference attacks. Our method also had fewer side effects in terms of generating new sensitive rules ratios than the traditional spatial-temporal k-anonymity method, and had basically the same side effects in terms of non-sensitive rules variation ratios with the traditional spatial-temporal k-anonymity method. Furthermore, we also found the performance variation tendency from the parameter K value, which can help achieve the goal of hiding the maximum number of original sensitive rules while generating a minimum of new sensitive rules and affecting a minimum number of non-sensitive rules. PMID:28767687

Train stimulation of parallel fibre to Purkinje cell inputs reveals two populations of synaptic responses with different receptor signatures

PubMed Central

Devi, Suma Priya Sudarsana; Howe, James R.

2016-01-01

Key points Purkinje cells of the cerebellum receive ∼180,000 parallel fibre synapses, which have often been viewed as a homogeneous synaptic population and studied using single action potentials.Many parallel fibre synapses might be silent, however, and granule cells in vivo fire in bursts. Here, we used trains of stimuli to study parallel fibre inputs to Purkinje cells in rat cerebellar slices.Analysis of train EPSCs revealed two synaptic components, phase 1 and 2. Phase 1 is initially large and saturates rapidly, whereas phase 2 is initially small and facilitates throughout the train. The two components have a heterogeneous distribution at dendritic sites and different pharmacological profiles.The differential sensitivity of phase 1 and phase 2 to inhibition by pentobarbital and NBQX mirrors the differential sensitivity of AMPA receptors associated with the transmembrane AMPA receptor regulatory protein, γ‐2, gating in the low‐ and high‐open probability modes, respectively. Abstract Cerebellar granule cells fire in bursts, and their parallel fibre axons (PFs) form ∼180,000 excitatory synapses onto the dendritic tree of a Purkinje cell. As many as 85% of these synapses have been proposed to be silent, but most are labelled for AMPA receptors. Here, we studied PF to Purkinje cell synapses using trains of 100 Hz stimulation in rat cerebellar slices. The PF train EPSC consisted of two components that were present in variable proportions at different dendritic sites: one, with large initial EPSC amplitude, saturated after three stimuli and dominated the early phase of the train EPSC; and the other, with small initial amplitude, increased steadily throughout the train of 10 stimuli and dominated the late phase of the train EPSC. The two phases also displayed different pharmacological profiles. Phase 2 was less sensitive to inhibition by NBQX but more sensitive to block by pentobarbital than phase 1. Comparison of synaptic results with fast glutamate applications to recombinant receptors suggests that the high‐open‐probability gating mode of AMPA receptors containing the auxiliary subunit transmembrane AMPA receptor regulatory protein γ‐2 makes a substantial contribution to phase 2. We argue that the two synaptic components arise from AMPA receptors with different functional signatures and synaptic distributions. Comparisons of voltage‐ and current‐clamp responses obtained from the same Purkinje cells indicate that phase 1 of the EPSC arises from synapses ideally suited to transmit short bursts of action potentials, whereas phase 2 is likely to arise from low‐release‐probability or ‘silent’ synapses that are recruited during longer bursts. PMID:27094216

Phase-sensitive, through-amplification with a double-pumped JPC

NASA Astrophysics Data System (ADS)

Sliwa, K. M.; Hatridge, M.; Frattini, N. E.; Narla, A.; Shankar, S.; Devoret, M. H.

The Josephson Parametric Converter (JPC) is now routinely used as a quantum-limited signal processing device for superconducting qubit experiments. The JPC consists of two modes, the signal and the idler, that are coupled by a ring of Josephson junctions that implements a non-degenerate, three-wave mixing process. This device is conventionally operated as either a phase-preserving parametric amplifier, or a coherent frequency converter, by pumping it at the sum or difference of the signal and idler frequencies, respectively. Here we present a novel double-pumping scheme based on theory by Metelmann and Clerk where a coherent conversion process and a gain process are simultaneously imposed between the signal and idler modes. The interference of these two processes results in a phase-sensitive amplifier with only forward gain, and which breaks the traditional gain-bandwidth limit of parametric amplification. We present results on phase-sensitive amplification with increased bandwidth, and on noise performance and dynamic range that are comparable to the traditional mode of operation. Work supported by ARO, AFOSR, NSF and YINQE.

Two-step Raman spectroscopy method for tumor diagnosis

NASA Astrophysics Data System (ADS)

Zakharov, V. P.; Bratchenko, I. A.; Kozlov, S. V.; Moryatov, A. A.; Myakinin, O. O.; Artemyev, D. N.

2014-05-01

Two-step Raman spectroscopy phase method was proposed for differential diagnosis of malignant tumor in skin and lung tissue. It includes detection of malignant tumor in healthy tissue on first step with identification of concrete cancer type on the second step. Proposed phase method analyze spectral intensity alteration in 1300-1340 and 1640-1680 cm-1 Raman bands in relation to the intensity of the 1450 cm-1 band on first step, and relative differences between RS intensities for tumor area and healthy skin closely adjacent to the lesion on the second step. It was tested more than 40 ex vivo samples of lung tissue and more than 50 in vivo skin tumors. Linear Discriminant Analysis, Quadratic Discriminant Analysis and Support Vector Machine were used for tumors type classification on phase planes. It is shown that two-step phase method allows to reach 88.9% sensitivity and 87.8% specificity for malignant melanoma diagnosis (skin cancer); 100% sensitivity and 81.5% specificity for adenocarcinoma diagnosis (lung cancer); 90.9% sensitivity and 77.8% specificity for squamous cell carcinoma diagnosis (lung cancer).

Preparation of Ion Exchange Films for Solid-Phase Spectrophotometry and Solid-Phase Fluorometry

NASA Technical Reports Server (NTRS)

Hill, Carol M.; Street, Kenneth W.; Tanner, Stephen P.; Philipp, Warren H.

2000-01-01

Atomic spectroscopy has dominated the field of trace inorganic analysis because of its high sensitivity and selectivity. The advantages gained by the atomic spectroscopies come with the disadvantage of expensive and often complicated instrumentation. Solid-phase spectroscopy, in which the analyte is preconcentrated on a solid medium followed by conventional spectrophotometry or fluorometry, requires less expensive instrumentation and has considerable sensitivity and selectivity. The sensitivity gains come from preconcentration and the use of chromophore (or fluorophore) developers and the selectivity is achieved by use of ion exchange conditions that favor the analyte in combination with speciative chromophores. Little work has been done to optimize the ion exchange medium (IEM) associated with these techniques. In this report we present a method for making ion exchange polymer films, which considerably simplify the solid-phase spectroscopic techniques. The polymer consists of formaldehyde-crosslinked polyvinyl alcohol with polyacrylic acid entrapped therein. The films are a carboxylate weak cation exchanger in the calcium form. They are mechanically sturdy and optically transparent in the ultraviolet and visible portion of the spectrum, which makes them suitable for spectrophotometry and fluorometry.

Novel experimental design for high pressure-high temperature electrical resistance measurements in a "Paris-Edinburgh" large volume press.

PubMed

Matityahu, Shlomi; Emuna, Moran; Yahel, Eyal; Makov, Guy; Greenberg, Yaron

2015-04-01

We present a novel experimental design for high sensitivity measurements of the electrical resistance of samples at high pressures (0-6 GPa) and high temperatures (300-1000 K) in a "Paris-Edinburgh" type large volume press. Uniquely, the electrical measurements are carried out directly on a small sample, thus greatly increasing the sensitivity of the measurement. The sensitivity to even minor changes in electrical resistance can be used to clearly identify phase transitions in material samples. Electrical resistance measurements are relatively simple and rapid to execute and the efficacy of the present experimental design is demonstrated by measuring the electrical resistance of Pb, Sn, and Bi across a wide domain of temperature-pressure phase space and employing it to identify the loci of phase transitions. Based on these results, the phase diagrams of these elements are reconstructed to high accuracy and found to be in excellent agreement with previous studies. In particular, by mapping the locations of several well-studied reference points in the phase diagram of Sn and Bi, it is demonstrated that a standard calibration exists for the temperature and pressure, thus eliminating the need for direct or indirect temperature and pressure measurements. The present technique will allow simple and accurate mapping of phase diagrams under extreme conditions and may be of particular importance in advancing studies of liquid state anomalies.

Application of a cholesterol stationary phase in the analysis of phosphorothioate oligonucleotides by means of ion pair chromatography coupled with tandem mass spectrometry.

PubMed

Studzińska, Sylwia; Krzemińska, Katarzyna; Szumski, Michał; Buszewski, Bogusław

2016-07-01

The main aim of this study was the investigation of the influence of several ion pair reagents towards both the retention and the mass spectrometry sensitivity of phosphorothioate oligonucleotides. A cholesterol stationary phase was applied for the first time in the analysis of this group of compounds. The mobile phase composition was modified by changing the concentration and the type of amines and acetates or 1,1,1,3,3,3-hexafluoroisopropanol. It has been shown that the increase of amines concentration results in the retention factor increase for each oligonucleotide, on each adsorbent. The only exception was the mobile phase composed of triethylamine and 1,1,1,3,3,3-hexafluoroisopropanol. This is a consequence of interactions taking place between a cholesterol molecule and an alcohol. This effect was convenient when the mass spectrometry detection was applied, since it allowed an increase in the sensitivity. Moreover, optimization of the mobile phase composition and its impact on the efficiency of ionization process and on the sensitivity in mass spectrometry were also presented. The optimization of this new method, based on cholesterol stationary phase coupled with mass spectrometry detection, was finally applied for the determination of phosphorothioate oligonucleotides impurity in a real sample. Copyright © 2016 Elsevier B.V. All rights reserved.

Feasibility of spectral-domain phase-sensitive optical coherence tomography for middle ear vibrometry

PubMed Central

Nguyen-Huynh, Anh; Wang, Ruikang K.; Jacques, Steven L.; Choudhury, Niloy; Nuttall, Alfred L.

2012-01-01

Abstract. We describe a novel application of spectral-domain phase-sensitive optical coherence tomography (SD PS-OCT) to detect the tiny motions of the middle ear structures, such as the tympanic membrane and ossicular chain, and their morphological features for differential diagnosis of CHL. This technique has the potential to provide meaningful vibration of ossicles with a vibration sensitivity of ∼0.5  nm at 1 kHz of acoustic stimulation. To the best of our knowledge, this is the first demonstration of depth-resolved vibration imaging of ossicles with a PS-OCT system at a nanometer scale. PMID:22734728

Comparison of Atom Interferometers and Light Interferometers as Space-Based Gravitational Wave Detectors

NASA Technical Reports Server (NTRS)

Baker, John G.

2012-01-01

We consider a class of proposed gravitational wave detectors based on multiple atomic interferometers separated by large baselines and referenced by common laser systems. We compute the sensitivity limits of these detectors due to intrinsic phase noise of the light sources, non-inertial motion of the light sources, and atomic shot noise and compare them to sensitivity limits for traditional light interferometers. We find that atom interferometers and light interferometers are limited in a nearly identical way by intrinsic phase noise and that both require similar mitigation strategies (e.g. multiple arm instruments) to reach interesting sensitivities. The sensitivity limit from motion of the light sources is slightly different and favors the atom interferometers in the low-frequency limit, although the limit in both cases is severe.

High sensitivity rotation sensing based on tunable asymmetrical double-ring structure

NASA Astrophysics Data System (ADS)

Gu, Hong; Liu, Xiaoqing

2017-05-01

A very high sensitivity rotation sensor comprising a tunable asymmetrical double-ring structure (TADRS) coupled by a 3 × 3 coupler is presented. The phase difference caused by the TADRS between the counter-propagating waves is derived and discussed. At the resonant frequency, the phase shift difference has the maximum value when the light power in one cavity is amplified about 1.85 times while attenuated 79% in another. The maximum sensitivity of the TADRS sensor is two times larger than that of a single-ring structure. An experimental system is designed to verify the theoretical results and introduce the method of demodulation. The rotation sensor based on TADRS can enhance the sensitivity of the detection of the angular velocity by more than three orders of magnitude.

Comparison of atom interferometers and light interferometers as space-based gravitational wave detectors.

PubMed

Baker, John G; Thorpe, J I

2012-05-25

We consider a class of proposed gravitational-wave detectors based on multiple atomic interferometers separated by large baselines and referenced by common laser systems. We compute the sensitivity limits of these detectors due to intrinsic phase noise of the light sources, noninertial motion of the light sources, and atomic shot noise and compare them to sensitivity limits for traditional light interferometers. We find that atom interferometers and light interferometers are limited in a nearly identical way by intrinsic phase noise and that both require similar mitigation strategies (e.g., multiple-arm instruments) to reach interesting sensitivities. The sensitivity limit from motion of the light sources is slightly different and, in principle, favors the atom interferometers in the low-frequency limit, although the limit in both cases is severe.

Additional EIPC Study Analysis: Interim Report on High Priority Topics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hadley, Stanton W

Between 2010 and 2012 the Eastern Interconnection Planning Collaborative (EIPC) conducted a major long-term resource and transmission study of the Eastern Interconnection (EI). With guidance from a Stakeholder Steering Committee (SSC) that included representatives from the Eastern Interconnection States Planning Council (EISPC) among others, the project was conducted in two phases. Phase 1 involved a long-term capacity expansion analysis that involved creation of eight major futures plus 72 sensitivities. Three scenarios were selected for more extensive transmission- focused evaluation in Phase 2. Five power flow analyses, nine production cost model runs (including six sensitivities), and three capital cost estimations weremore » developed during this second phase. The results from Phase 1 and 2 provided a wealth of data that could be examined further to address energy-related questions. A list of 13 topics was developed for further analysis; this paper discusses the first five.« less

Improving Secondary Organic Aerosol (SOA) Models using Global Sensitivity Analysis and by Comparison to Chamber Data.

NASA Astrophysics Data System (ADS)

Miller, D. O.; Brune, W. H.

2017-12-01

Accurate estimates of secondary organic aerosol (SOA) from atmospheric models is a major research challenge due to the complexity of the chemical and physical processes involved in the SOA formation and continuous aging. The primary uncertainties of SOA models include those associated with the formation of gas-phase products, the conversion between gas phase and particle phase, the aging mechanisms of SOA, and other processes related to the heterogeneous and particle-phase reactions. To address this challenge, we us a modular modeling framework that combines both simple and near-explicit gas-phase reactions and a two-dimensional volatility basis set (2D-VBS) to simulate the formation and evolution of SOA. Global sensitivity analysis is used to assess the relative importance of the model input parameters. In addition, the model is compared to the measurements from the Focused Isoprene eXperiment at the California Institute of Technology (FIXCIT).

Broadband Phase Spectroscopy over Turbulent Air Paths

NASA Astrophysics Data System (ADS)

Giorgetta, Fabrizio R.; Rieker, Gregory B.; Baumann, Esther; Swann, William C.; Sinclair, Laura C.; Kofler, Jon; Coddington, Ian; Newbury, Nathan R.

2015-09-01

Broadband atmospheric phase spectra are acquired with a phase-sensitive dual-frequency-comb spectrometer by implementing adaptive compensation for the strong decoherence from atmospheric turbulence. The compensation is possible due to the pistonlike behavior of turbulence across a single spatial-mode path combined with the intrinsic frequency stability and high sampling speed associated with dual-comb spectroscopy. The atmospheric phase spectrum is measured across 2 km of air at each of the 70 000 comb teeth spanning 233 cm-1 across hundreds of near-infrared rovibrational resonances of CO2 , CH4 , and H2O with submilliradian uncertainty, corresponding to a 10-13 refractive index sensitivity. Trace gas concentrations extracted directly from the phase spectrum reach 0.7 ppm uncertainty, demonstrated here for CO2 . While conventional broadband spectroscopy only measures intensity absorption, this approach enables measurement of the full complex susceptibility even in practical open path sensing.

All-optical simultaneous multichannel quadrature phase shift keying signal regeneration based on phase-sensitive amplification

NASA Astrophysics Data System (ADS)

Wang, Hongxiang; Wang, Qi; Bai, Lin; Ji, Yuefeng

2018-01-01

A scheme is proposed to realize the all-optical phase regeneration of four-channel quadrature phase shift keying (QPSK) signal based on phase-sensitive amplification. By utilizing conjugate pump and common pump in a highly nonlinear optical fiber, degenerate four-wave mixing process is observed, and QPSK signals are regenerated. The number of waves is reduced to decrease the cross talk caused by undesired nonlinear interaction during the coherent superposition process. In addition, to avoid the effect of overlapping frequency, frequency spans between pumps and signals are set to be nonintegral multiples. Optical signal-to-noise ratio improvement is validated by bit error rate measurements. Compared with single-channel regeneration, multichannel regeneration brings 0.4-dB OSNR penalty when the value of BER is 10-3, which shows the cross talk in regeneration process is negligible.

Constitutive modeling of the dynamic-tensile-extrusion test of PTFE

NASA Astrophysics Data System (ADS)

Resnyansky, A. D.; Brown, E. N.; Trujillo, C. P.; Gray, G. T.

2017-01-01

Use of polymers in defense, aerospace and industrial applications under extreme loading conditions makes prediction of the behavior of these materials very important. Crucial to this is knowledge of the physical damage response in association with phase transformations during loading and the ability to predict this via multi-phase simulation accounting for thermodynamical non-equilibrium and strain rate sensitivity. The current work analyzes Dynamic-Tensile-Extrusion (Dyn-Ten-Ext) experiments on polytetrafluoroethylene (PTFE). In particular, the phase transition during loading and subsequent tension are analyzed using a two-phase rate sensitive material model implemented in the CTH hydrocode. The calculations are compared with experimental high-speed photography. Deformation patterns and their link with changing loading modes are analyzed numerically and correlated to the test observations. It is concluded that the phase transformation is not as critical to the response of PTFE under Dyn-Ten-Ext loading as it is during the Taylor rod impact testing.

Strain rate sensitivity of a TRIP-assisted dual-phase high-entropy alloy

NASA Astrophysics Data System (ADS)

Basu, Silva; Li, Zhiming; Pradeep, K. G.; Raabe, Dierk

2018-05-01

Dual-phase high-entropy alloys (DP-HEAs) with transformation induced plasticity (TRIP) have an excellent strength-ductility combination. To reveal their strain-rate sensitivity and hence further understand the corresponding deformation mechanisms, we investigated the tensile behavior and microstructural evolution of a typical TRIP-DP-HEA (Fe50Mn30Co10Cr10, at. %) under different strain rates (i.e., 5 × 10-3 s-1, 1 × 10-3 s-1, 5 × 10-4 s-1 and 1 × 10-4 s-1) at room temperature. The strain rate range was confined to this regime in order to apply the digital image correlation technique for probing the local strain evolution during tensile deformation at high resolution and to correlate it to the microstructure evolution. Grain size effects of the face-centered cubic (FCC) matrix and the volume fractions of the hexagonal-close packed (HCP) phase prior to deformation were also considered. The results show that within the explored strain rate regime the TRIP-DP-HEA has a fairly low strain rate sensitivity parameter within the range from 0.004 to 0.04, which is significantly lower than that of DP and TRIP steels. Samples with varying grain sizes (e.g., 2.8 μm and 38 μm) and starting HCP phase fractions (e.g., 25% and 72%) at different strain rates show similar deformation mechanisms, i.e., dislocation plasticity and strain-induced transformation from the FCC matrix to the HCP phase. The low strain rate sensitivity is attributed to the observed dominant displacive transformation mechanism. Also, the coarse-grained alloy samples with a very high starting HCP phase fraction ( 72%) prior to deformation show very good ductility with a total elongation of 60%, suggesting that both, the initial and the transformed HCP phase in the TRIP-DP-HEA are ductile and deform further via dislocation slip at the different strain rates which were probed.

Phase sensitive amplification in integrated waveguides (Conference Presentation)

NASA Astrophysics Data System (ADS)

Schroeder, Jochen B.; Zhang, Youngbin; Husko, Chad A.; LeFrancois, Simon; Eggleton, Benjamin J.

2017-02-01

Phase sensitive amplification (PSA) is an attractive technology for integrated all-optical signal processing, due to it's potential for noiseless amplification, phase regeneration and generation of squeezed light. In this talk I will review our results on implementing four-wave-mixing based PSA inside integrated photonic devices. In particular I will discuss PSA in chalcogenide ridge waveguides and silicon slow-light photonic crystals. We achieve PSA in both pump- and signal-degenerate schemes with maximum extinction ratios of 11 (silicon) and 18 (chalcogenide) dB. I will further discuss the influence of two-photon absorption and free carrier effects on the performance of silicon-based PSAs.

Birefringence measurement of retinal nerve fiber layer using polarization-sensitive spectral domain optical coherence tomography with Jones matrix based analysis

NASA Astrophysics Data System (ADS)

Yamanari, Masahiro; Miura, Masahiro; Makita, Shuichi; Yatagai, Toyohiko; Yasuno, Yoshiaki

2007-02-01

Birefringence of retinal nerve fiber layer is measured by polarization-sensitive spectral domain optical coherence tomography using the B-scan-oriented polarization modulation method. Birefringence of the optical fiber and the cornea is compensated by Jones matrix based analysis. Three-dimensional phase retardation map around the optic nerve head and en-face phase retardation map of the retinal nerve fiber layer are shown. Unlike scanning laser polarimetry, our system can measure the phase retardation quantitatively without using bow-tie pattern of the birefringence in the macular region, which enables diagnosis of glaucoma even if the patients have macular disease.

Orientationally ordered colloidal co-dispersions of gold nanorods and cellulose nanocrystals.

PubMed

Liu, Qingkun; Campbell, Michael G; Evans, Julian S; Smalyukh, Ivan I

2014-11-12

Nematic-like and helicoidally orientational self-assemblies of gold nanorods co-dispersed with cellulose nanocrystals to form liquid crystalline phases are developed. Polarization-sensitive extinction spectra and two-photon luminescence imaging are used to characterize orientations and spatial distributions of gold nanorods. Cholesteric-isotropic phase coexistence and continuous domains of single-phase regions are observed and qualitatively discussed on the basis of entropic and electrostatic interactions in co-dispersions of rigid rods of different aspect ratios. Potential applications include biologically compatible plasmonic composite nanomaterials for solar biofuel production and polarization-sensitive plasmonic papers and fabrics. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Analog phase lock between two lasers at LISA power levels

NASA Astrophysics Data System (ADS)

Diekmann, Christian; Steier, Frank; Sheard, Benjamin; Heinzel, Gerhard; Danzmann, Karsten

2009-03-01

This paper presents the implementation of an analog optical phase-locked-loop with an offset frequency of about 20MHz between two lasers, where the detected light powers were of the order of 31 pW and 200 μW. The goal of this setup was the design and characterization of a photodiode transimpedance amplifier for application in LISA. By application of a transimpedance amplifier designed to have low noise and low power consumption, the phase noise between the two lasers was a factor of two above the shot noise limit down to 60mHz. The achievable phase sensitivity depends ultimately on the available power of the highly attenuated master laser and on the input current noise of the transimpedance amplifier of the photodetector. The limiting noise source below 60mHz was the analog phase measurement system that was used in this experiment. A digital phase measurement system that is currently under development at the AEI will be used in the near future. Its application should improve the sensitivity.

Wavefront image sensor chip

PubMed Central

Cui, Xiquan; Ren, Jian; Tearney, Guillermo J.; Yang, Changhuei

2010-01-01

We report the implementation of an image sensor chip, termed wavefront image sensor chip (WIS), that can measure both intensity/amplitude and phase front variations of a light wave separately and quantitatively. By monitoring the tightly confined transmitted light spots through a circular aperture grid in a high Fresnel number regime, we can measure both intensity and phase front variations with a high sampling density (11 µm) and high sensitivity (the sensitivity of normalized phase gradient measurement is 0.1 mrad under the typical working condition). By using WIS in a standard microscope, we can collect both bright-field (transmitted light intensity) and normalized phase gradient images. Our experiments further demonstrate that the normalized phase gradient images of polystyrene microspheres, unstained and stained starfish embryos, and strongly birefringent potato starch granules are improved versions of their corresponding differential interference contrast (DIC) microscope images in that they are artifact-free and quantitative. Besides phase microscopy, WIS can benefit machine recognition, object ranging, and texture assessment for a variety of applications. PMID:20721059

Imaging Polarimetry in Age-Related Macular Degeneration

PubMed Central

Miura, Masahiro; Yamanari, Masahiro; Iwasaki, Takuya; Elsner, Ann E.; Makita, Shuichi; Yatagai, Toyohiko; Yasuno, Yoshiaki

2010-01-01

PURPOSE To evaluate the birefringence properties of eyes with age-related macular degeneration (AMD). To compare the information from two techniques—scanning laser polarimetry (GDx) and polarization-sensitive spectral-domain optical coherence tomography (OCT)—and investigate how they complement each other. METHODS The authors prospectively examined the eyes of two healthy subjects and 13 patients with exudative AMD. Using scanning laser polarimetry, they computed phase-retardation maps, average reflectance images, and depolarized light images. To obtain polarimetry information with improved axial resolution, they developed a fiber-based, polarization-sensitive, spectral-domain OCT system and measured the phase retardation associated with birefringence in the same eyes. RESULTS Both GDx and polarization-sensitive spectral-domain optical coherence tomography detected abnormal birefringence at the locus of exudative lesions. Polarization-sensitive, spectral-domain OCT showed that in the old lesions with fibrosis, phase-retardation values were significantly larger than in the new lesions (P = 0.020). Increased scattered light and altered polarization scramble were associated with portions of the lesions. CONCLUSIONS GDx and polarization-sensitive spectral-domain OCT are complementary in probing birefringence properties in exudative AMD. Polarimetry findings in exudative AMD emphasized different features and were related to the progression of the disease, potentially providing a noninvasive tool for microstructure in exudative AMD. PMID:18515594

Choosing between atmospheric pressure chemical ionization and electrospray ionization interfaces for the HPLC/MS analysis of pesticides

USGS Publications Warehouse

Thurman, E.M.; Ferrer, I.; Barcelo, D.

2001-01-01

An evaluation of over 75 pesticides by high-performance liquid chromatography/mass spectrometry (HPLC/MS) clearly shows that different classes of pesticides are more sensitive using either atmospheric pressure chemical ionization (APCI) or electrospray ionization (ESI). For example, neutral and basic pesticides (phenylureas, triazines) are more sensitive using APCI (especially positive ion). While cationic and anionic herbicides (bipyridylium ions, sulfonic acids) are more sensitive using ESI (especially negative ion). These data are expressed graphically in a figure called an ionization-continuum diagram, which shows that protonation in the gas phase (proton affinity) and polarity in solution, expressed as proton addition or subtraction (pKa), is useful in selecting APCI or ESI. Furthermore, sodium adduct formation commonly occurs using positive ion ESI but not using positive ion APCI, which reflects the different mechanisms of ionization and strengthens the usefulness of the ionization-continuum diagram. The data also show that the concept of "wrong-way around" ESI (the sensitivity of acidic pesticides in an acidic mobile phase) is a useful modification of simple pKa theory for mobile-phase selection. Finally, this finding is used to enhance the chromatographic separation of oxanilic and sulfonic acid herbicides while maintaining good sensitivity in LC/MS using ESI negative.

Polarization-sensitive optical coherence tomography using continuous polarization modulation with arbitrary phase modulation amplitude

NASA Astrophysics Data System (ADS)

Lu, Zenghai; Kasaragod, Deepa K.; Matcher, Stephen J.

2012-03-01

We demonstrate theoretically and experimentally that the phase retardance and relative optic-axis orientation of a sample can be calculated without prior knowledge of the actual value of the phase modulation amplitude when using a polarization-sensitive optical coherence tomography system based on continuous polarization modulation (CPM-PS-OCT). We also demonstrate that the sample Jones matrix can be calculated at any values of the phase modulation amplitude in a reasonable range depending on the system effective signal-to-noise ratio. This has fundamental importance for the development of clinical systems by simplifying the polarization modulator drive instrumentation and eliminating its calibration procedure. This was validated on measurements of a three-quarter waveplate and an equine tendon sample by a fiber-based swept-source CPM-PS-OCT system.

A phased antenna array for surface plasmons

PubMed Central

Dikken, Dirk Jan W.; Korterik, Jeroen P.; Segerink, Frans B.; Herek, Jennifer L.; Prangsma, Jord C.

2016-01-01

Surface plasmon polaritons are electromagnetic waves that propagate tightly bound to metal surfaces. The concentration of the electromagnetic field at the surface as well as the short wavelength of surface plasmons enable sensitive detection methods and miniaturization of optics. We present an optical frequency plasmonic analog to the phased antenna array as it is well known in radar technology and radio astronomy. Individual holes in a thick gold film act as dipolar emitters of surface plasmon polaritons whose phase is controlled individually using a digital spatial light modulator. We show experimentally, using a phase sensitive near-field microscope, that this optical system allows accurate directional emission of surface waves. This compact and flexible method allows for dynamically shaping the propagation of plasmons and holds promise for nanophotonic applications employing propagating surface plasmons. PMID:27121099

Artifact Suppression in Imaging of Myocardial Infarction Using B1-Weighted Phased-Array Combined Phase-Sensitive Inversion Recovery

PubMed Central

Kellman, Peter; Dyke, Christopher K.; Aletras, Anthony H.; McVeigh, Elliot R.; Arai, Andrew E.

2007-01-01

Regions of the body with long T1, such as cerebrospinal fluid (CSF), may create ghost artifacts on gadolinium-hyperenhanced images of myocardial infarction when inversion recovery (IR) sequences are used with a segmented acquisition. Oscillations in the transient approach to steady state for regions with long T1 may cause ghosts, with the number of ghosts being equal to the number of segments. B1-weighted phased-array combining provides an inherent degree of ghost artifact suppression because the ghost artifact is weighted less than the desired signal intensity by the coil sensitivity profiles. Example images are shown that illustrate the suppression of CSF ghost artifacts by the use of B1-weighted phased-array combining of multiple receiver coils. PMID:14755669

Constitutive Modeling of the Dynamic-Tensile-Extrusion Test of PTFE

NASA Astrophysics Data System (ADS)

Resnyansky, Anatoly; Brown, Eric; Trujillo, Carl; Gray, George

2015-06-01

Use of polymers in the defence, aerospace and industrial application at extreme conditions makes prediction of behaviour of these materials very important. Crucial to this is knowledge of the physical damage response in association with the phase transformations during the loading and the ability to predict this via multi-phase simulation taking the thermodynamical non-equilibrium and strain rate sensitivity into account. The current work analyses Dynamic-Tensile-Extrusion (DTE) experiments on polytetrafluoroethylene (PTFE). In particular, the phase transition during the loading with subsequent tension are analysed using a two-phase rate sensitive material model implemented in the CTH hydrocode and the calculations are compared with experimental high-speed photography. The damage patterns and their link with the change of loading modes are analysed numerically and are correlated to the test observations.

Phase calibration target for quantitative phase imaging with ptychography.

PubMed

Godden, T M; Muñiz-Piniella, A; Claverley, J D; Yacoot, A; Humphry, M J

2016-04-04

Quantitative phase imaging (QPI) utilizes refractive index and thickness variations that lead to optical phase shifts. This gives contrast to images of transparent objects. In quantitative biology, phase images are used to accurately segment cells and calculate properties such as dry mass, volume and proliferation rate. The fidelity of the measured phase shifts is of critical importance in this field. However to date, there has been no standardized method for characterizing the performance of phase imaging systems. Consequently, there is an increasing need for protocols to test the performance of phase imaging systems using well-defined phase calibration and resolution targets. In this work, we present a candidate for a standardized phase resolution target, and measurement protocol for the determination of the transfer of spatial frequencies, and sensitivity of a phase imaging system. The target has been carefully designed to contain well-defined depth variations over a broadband range of spatial frequencies. In order to demonstrate the utility of the target, we measure quantitative phase images on a ptychographic microscope, and compare the measured optical phase shifts with Atomic Force Microscopy (AFM) topography maps and surface profile measurements from coherence scanning interferometry. The results show that ptychography has fully quantitative nanometer sensitivity in optical path differences over a broadband range of spatial frequencies for feature sizes ranging from micrometers to hundreds of micrometers.

SSTs from Fossil Corals using Sr-U Thermometry

NASA Astrophysics Data System (ADS)

Cohen, A. L.; Alpert, A.; Soucy, A.; DeCarlo, T. M.; Vasquez-Bedoya, L. F.; Blanchon, P.; Oppo, D.; Gaetani, G. A.

2017-12-01

Earth's climate varies naturally on decadal through millennial timescales. Resolving and attributing the anthropogenic influence on climate therefore, requires accurate, continuous records that exceed the duration of the short observational dataset. Sea surface temperatures (SSTs) of warm tropical regions are especially important because the tropics are regions of deep atmospheric convection that redistribute heat and moisture. The skeletons of long-lived corals are valuable archives of tropical ocean temperature, yet the pre-instrumental SST evolution of the global tropical oceans remains poorly constrained. One reason is the limited lifespan of individual coral colonies, which seldom exceeds 150-200 years. Thus, extending SST records well beyond the observational period requires use of well-dated sub-fossil material but the current coral-based temperature proxy, Sr/Ca, is not well-suited for application to non-living material. The sensitivity of the Sr/Ca-SST relationship can vary from coral to coral, limiting the accuracy with which absolute temperature and trends can be interpreted from non-living corals. To overcome this constraint, we developed a new thermometer, Sr-U, based on a robust understanding of the processes responsible for colony-to-colony variability. Our Sr-U SST calibration is derived from three coral species representing two Atlantic and one Pacific site, validated against the instrumental record of SST and spanning a temperature range of 24.5 through 28.5 °C. We applied Sr-U to U-series dated fossil corals that grew on tropical Atlantic reefs during the Little Ice Age (1450-1650 AD) and Last Interglacial (122 000 yr BP). Our results show that SSTs in the region fluctuated within 1°C of modern values, with much of the late LIA slightly cooler and the LIG slightly warmer than late 20th century SSTs. Each continuous coral-based record spans multiple decades, enabling us to identify multi-decadal AMO-like variability as a persistent characteristic of tropical Atlantic variability.

Interaural Phase and Level Difference Sensitivity in Low-Frequency Neurons in the Lateral Superior Olive

PubMed Central

Tollin, Daniel J.; Yin, Tom C. T.

2006-01-01

The lateral superior olive (LSO) is believed to encode differences in sound level at the two ears, a cue for azimuthal sound location. Most high-frequency-sensitive LSO neurons are binaural, receiving inputs from both ears. An inhibitory input from the contralateral ear, via the medial nucleus of the trapezoid body (MNTB), and excitatory input from the ipsilateral ear enable level differences to be encoded. However, the classical descriptions of low-frequency-sensitive neurons report primarily monaural cells with no contralateral inhibition. Anatomical and physiological evidence, however, shows that low-frequency LSO neurons receive low-frequency inhibitory input from ipsilateral MNTB, which in turn receives excitatory input from the contralateral cochlear nucleus and low-frequency excitatory input from the ipsilateral cochlear nucleus. Therefore, these neurons would be expected to be binaural with contralateral inhibition. Here, we re-examined binaural interaction in low-frequency (less than ~3 kHz) LSO neurons and phase locking in the MNTB. Phase locking to low-frequency tones in MNTB and ipsilaterally driven LSO neurons with frequency sensitivities < 1.2 kHz was enhanced relative to the auditory nerve. Moreover, most low-frequency LSO neurons exhibited contralateral inhibition: ipsilaterally driven responses were suppressed by raising the level of the contralateral stimulus; most neurons were sensitive to interaural time delays in pure tone and noise stimuli such that inhibition was nearly maximal when the stimuli were presented to the ears in-phase. The data demonstrate that low-frequency LSO neurons of cat are not monaural and can exhibit contralateral inhibition like their high-frequency counterparts. PMID:16291937

Phase behavior of dioleyphosphatidylethanolamine molecules in the presence of components of pH-sensitive liposomes and paclitaxel.

PubMed

Monteiro, Liziane O F; Lopes, Sávia C A; Barros, André Luís B; Magalhães-Paniago, Rogério; Malachias, Ângelo; Oliveira, Mônica C; Leite, Elaine A

2016-08-01

Paclitaxel is a potent antimicrotubule chemotherapeutic agent widely used for clinical treatment of a variety of solid tumors. However, the low solubility of the drug in aqueous medium and the toxic effects of the commercially available formulation, Taxol(®), has hindered its clinical application. To overcome these paclitaxel-related disadvantages, several drug delivery approaches have been thoroughly investigated. In this context, our research group has developed long-circulating and pHsensitive liposomes containing paclitaxel composed of dioleylphosphatidylethanolamine, cholesterylhemisuccinate and distearoylphosphatidylethanolamine-polyethylene glycol2000, which have shown to be very promising carriers for this taxane. For the destabilization of pH-sensitive liposomal systems and the release of the encapsulated drug in the cytoplasm of tumor cells, the occurrence of a phase transition from a lamellar to a non-lamellar phase of dioleylphosphatidylethanolamine molecules is essential. Two techniques, differential scanning calorimetry and small angle X-ray scattering, were used to investigate the influence of the liposomal components and paclitaxel in the phase transition process of dioleylphosphatidylethanolamine molecules and to evaluate the pH-sensitivity of the formulation under low hydration conditions. The findings clearly evidence the phase transition of dioleylphosphatidylethanolamine molecules in the presence and absence of PTX indicating that the introduction of the drug in the system does not bring damage to the pH-sensitivity of the system, which resulting in liposome destabilization at low pH regions and encapsulated paclitaxel release preferentially in a desired target tissue. Copyright © 2016 Elsevier B.V. All rights reserved.