Isolation of novel ribozymes that ligate AMP-activated RNA substrates

NASA Technical Reports Server (NTRS)

Hager, A. J.; Szostak, J. W.

1997-01-01

BACKGROUND: The protein enzymes RNA ligase and DNA ligase catalyze the ligation of nucleic acids via an adenosine-5'-5'-pyrophosphate 'capped' RNA or DNA intermediate. The activation of nucleic acid substrates by adenosine 5'-monophosphate (AMP) may be a vestige of 'RNA world' catalysis. AMP-activated ligation seems ideally suited for catalysis by ribozymes (RNA enzymes), because an RNA motif capable of tightly and specifically binding AMP has previously been isolated. RESULTS: We used in vitro selection and directed evolution to explore the ability of ribozymes to catalyze the template-directed ligation of AMP-activated RNAs. We subjected a pool of 10(15) RNA molecules, each consisting of long random sequences flanking a mutagenized adenosine triphosphate (ATP) aptamer, to ten rounds of in vitro selection, including three rounds involving mutagenic polymerase chain reaction. Selection was for the ligation of an oligonucleotide to the 5'-capped active pool RNA species. Many different ligase ribozymes were isolated; these ribozymes had rates of reaction up to 0.4 ligations per hour, corresponding to rate accelerations of approximately 5 x10(5) over the templated, but otherwise uncatalyzed, background reaction rate. Three characterized ribozymes catalyzed the formation of 3'-5'-phosphodiester bonds and were highly specific for activation by AMP at the ligation site. CONCLUSIONS: The existence of a new class of ligase ribozymes is consistent with the hypothesis that the unusual mechanism of the biological ligases resulted from a conservation of mechanism during an evolutionary replacement of a primordial ribozyme ligase by a more modern protein enzyme. The newly isolated ligase ribozymes may also provide a starting point for the isolation of ribozymes that catalyze the polymerization of AMP-activated oligonucleotides or mononucleotides, which might have been the prebiotic analogs of nucleoside triphosphates.

A protein tyrosine phosphatase-like protein from baculovirus has RNA 5′-triphosphatase and diphosphatase activities

PubMed Central

Takagi, Toshimitsu; Taylor, Gregory S.; Kusakabe, Takahiro; Charbonneau, Harry; Buratowski, Stephen

1998-01-01

The superfamily of protein tyrosine phosphatases (PTPs) includes at least one enzyme with an RNA substrate. We recently showed that the RNA triphosphatase domain of the Caenorhabditis elegans mRNA capping enzyme is related to the PTP enzyme family by sequence similarity and mechanism. The PTP most similar in sequence to the capping enzyme triphosphatase is BVP, a dual-specificity PTP encoded by the Autographa californica nuclear polyhedrosis virus. Although BVP previously has been shown to have modest tyrosine and serine/threonine phosphatase activity, we find that it is much more potent as an RNA 5′-phosphatase. BVP sequentially removes γ and β phosphates from the 5′ end of triphosphate-terminated RNA, leaving a 5′-monophosphate end. The activity was specific for polynucleotides; nucleotide triphosphates were not hydrolyzed. A mutant protein in which the active site cysteine was replaced with serine was inactive. Three other dual-specificity PTPs (VH1, VHR, and Cdc14) did not exhibit detectable RNA phosphatase activity. Therefore, capping enzyme and BVP are members of a distinct PTP-like subfamily that can remove phosphates from RNA. PMID:9707557

Promotion of Testa Rupture during Garden Cress Germination Involves Seed Compartment-Specific Expression and Activity of Pectin Methylesterases1[OPEN

PubMed Central

Scheler, Claudia; Weitbrecht, Karin; Pearce, Simon P.; Hampstead, Anthony; Büttner-Mainik, Annette; Lee, Kieran J.D.; Voegele, Antje; Oracz, Krystyna; Dekkers, Bas J.W.; Wang, Xiaofeng; Wood, Andrew T.A.; Bentsink, Leónie; King, John R.; Knox, J. Paul; Holdsworth, Michael J.; Müller, Kerstin; Leubner-Metzger, Gerhard

2015-01-01

Pectin methylesterase (PME) controls the methylesterification status of pectins and thereby determines the biophysical properties of plant cell walls, which are important for tissue growth and weakening processes. We demonstrate here that tissue-specific and spatiotemporal alterations in cell wall pectin methylesterification occur during the germination of garden cress (Lepidium sativum). These cell wall changes are associated with characteristic expression patterns of PME genes and resultant enzyme activities in the key seed compartments CAP (micropylar endosperm) and RAD (radicle plus lower hypocotyl). Transcriptome and quantitative real-time reverse transcription-polymerase chain reaction analysis as well as PME enzyme activity measurements of separated seed compartments, including CAP and RAD, revealed distinct phases during germination. These were associated with hormonal and compartment-specific regulation of PME group 1, PME group 2, and PME inhibitor transcript expression and total PME activity. The regulatory patterns indicated a role for PME activity in testa rupture (TR). Consistent with a role for cell wall pectin methylesterification in TR, treatment of seeds with PME resulted in enhanced testa permeability and promoted TR. Mathematical modeling of transcript expression changes in germinating garden cress and Arabidopsis (Arabidopsis thaliana) seeds suggested that group 2 PMEs make a major contribution to the overall PME activity rather than acting as PME inhibitors. It is concluded that regulated changes in the degree of pectin methylesterification through CAP- and RAD-specific PME and PME inhibitor expression play a crucial role during Brassicaceae seed germination. PMID:25429110

NF-KappaB2/p52 Activation and Androgen Receptor Signaling in Prostate Cancer

DTIC Science & Technology

2011-08-01

biosynthetic enzymes including AKR1C3, CYP17A1, HSD3B2, and SRD5A1 were found to be elevated in CaP cells expressing NF-kappaB2/p52. Luciferase assays...RESULTS: Expression levels of androgen biosynthetic enzymes including AKR1C3, CYP17A1, HSD3B2, and SRD5A1 were found to be elevated in CaP cells

Development of cleaved amplified polymorphic sequence markers and a CAPS-based genetic linkage map in watermelon (Citrullus lanatus [Thunb.] Matsum. and Nakai) constructed using whole-genome re-sequencing data

PubMed Central

Liu, Shi; Gao, Peng; Zhu, Qianglong; Luan, Feishi; Davis, Angela R.; Wang, Xiaolu

2016-01-01

Cleaved amplified polymorphic sequence (CAPS) markers are useful tools for detecting single nucleotide polymorphisms (SNPs). This study detected and converted SNP sites into CAPS markers based on high-throughput re-sequencing data in watermelon, for linkage map construction and quantitative trait locus (QTL) analysis. Two inbred lines, Cream of Saskatchewan (COS) and LSW-177 had been re-sequenced and analyzed by Perl self-compiled script for CAPS marker development. 88.7% and 78.5% of the assembled sequences of the two parental materials could map to the reference watermelon genome, respectively. Comparative assembled genome data analysis provided 225,693 and 19,268 SNPs and indels between the two materials. 532 pairs of CAPS markers were designed with 16 restriction enzymes, among which 271 pairs of primers gave distinct bands of the expected length and polymorphic bands, via PCR and enzyme digestion, with a polymorphic rate of 50.94%. Using the new CAPS markers, an initial CAPS-based genetic linkage map was constructed with the F2 population, spanning 1836.51 cM with 11 linkage groups and 301 markers. 12 QTLs were detected related to fruit flesh color, length, width, shape index, and brix content. These newly CAPS markers will be a valuable resource for breeding programs and genetic studies of watermelon. PMID:27162496

New insights into respirable protein powder preparation using a nano spray dryer.

PubMed

Bürki, K; Jeon, I; Arpagaus, C; Betz, G

2011-04-15

In this study the Nano Spray Dryer B-90 (BÜCHI Labortechnik AG, Flawil, Switzerland) was evaluated with regard to the drying of proteins and the preparation of respirable powders in the size range of 1-5 μm. β-galactosidase was chosen as a model protein and trehalose was added as a stabilizer. The influence of inlet temperature, hole size of the spray cap membrane and ethanol concentration in the spray solution was studied using a 3³ full factorial design. The investigated responses were enzyme activity, particle size, span, yield and shelf life. Furthermore, the particle morphology was examined. The inlet temperature as well as the interaction of inlet temperature and spray cap size significantly influenced the enzyme activity. Full activity was retained with the optimized process. The particle size was affected by the hole size of the spray cap membrane and the ethanol content. The smallest cap led to a monodisperse particle size distribution and the greatest yield of particles of respirable size. Higher product recovery was achieved with lower inlet temperatures, higher ethanol contents and smaller cap sizes. Particle morphology differed depending on the cap size. The protein exhibited higher storage stability when spray dried without ethanol and when a larger spray cap size was used. Copyright © 2011 Elsevier B.V. All rights reserved.

DNA 3' pp 5' G de-capping activity of aprataxin: effect of cap nucleoside analogs and structural basis for guanosine recognition

DOE PAGES

Chauleau, Mathieu; Jacewicz, Agata; Shuman, Stewart

2015-05-24

DNA 3' pp 5'G caps synthesized by the 3'-PO 4/5'-OH ligase RtcB have a strong impact on enzymatic reactions at DNA 3'-OH ends. Aprataxin, an enzyme that repairs A5'pp5'DNA ends formed during abortive ligation by classic 3'-OH/5'-PO 4 ligases, is also a DNA 3' de-capping enzyme, converting DNAppG to DNA 3'p and GMP. By taking advantage of RtcB's ability to utilize certain GTP analogs to synthesize DNAppN caps, we show that aprataxin hydrolyzes inosine and 6-O-methylguanosine caps, but is not adept at removing a deoxyguanosine cap. We report a 1.5 Å crystal structure of aprataxin in a complex with GMP,more » which reveals that: (i) GMP binds at the same position and in the same anti nucleoside conformation as AMP; and (ii) aprataxin makes more extensive nucleobase contacts with guanine than with adenine, via a hydrogen bonding network to the guanine O6, N1, N2 base edge. Alanine mutations of catalytic residues His147 and His149 abolish DNAppG de-capping activity, suggesting that the 3' de-guanylylation and 5' de-adenylylation reactions follow the same pathway of nucleotidyl transfer through a covalent aprataxin-(His147)–NMP intermediate. Alanine mutation of Asp63, which coordinates the guanosine ribose hydroxyls, impairs DNAppG de-capping.« less

Adenosine kinase modulates root gravitropism and cap morphogenesis in Arabidopsis.

PubMed

Young, Li-Sen; Harrison, Benjamin R; Narayana Murthy, U M; Moffatt, Barbara A; Gilroy, Simon; Masson, Patrick H

2006-10-01

Adenosine kinase (ADK) is a key enzyme that regulates intra- and extracellular levels of adenosine, thereby modulating methyltransferase reactions, production of polyamines and secondary compounds, and cell signaling in animals. Unfortunately, little is known about ADK's contribution to the regulation of plant growth and development. Here, we show that ADK is a modulator of root cap morphogenesis and gravitropism. Upon gravistimulation, soluble ADK levels and activity increase in the root tip. Mutation in one of two Arabidopsis (Arabidopsis thaliana) ADK genes, ADK1, results in cap morphogenesis defects, along with alterations in root sensitivity to gravistimulation and slower kinetics of root gravitropic curvature. The kinetics defect can be partially rescued by adding spermine to the growth medium, whereas the defects in cap morphogenesis and gravitropic sensitivity cannot. The root morphogenesis and gravitropism defects of adk1-1 are accompanied by altered expression of the PIN3 auxin efflux facilitator in the cap and decreased expression of the auxin-responsive DR5-GUS reporter. Furthermore, PIN3 fails to relocalize to the bottom membrane of statocytes upon gravistimulation. Consequently, adk1-1 roots cannot develop a lateral auxin gradient across the cap, necessary for the curvature response. Interestingly, adk1-1 does not affect gravity-induced cytoplasmic alkalinization of the root statocytes, suggesting either that ADK1 functions between cytoplasmic alkalinization and PIN3 relocalization in a linear pathway or that the pH and PIN3-relocalization responses to gravistimulation belong to distinct branches of the pathway. Our data are consistent with a role for ADK and the S-adenosyl-L-methionine pathway in the control of root gravitropism and cap morphogenesis.

Adenosine Kinase Modulates Root Gravitropism and Cap Morphogenesis in Arabidopsis1[W][OA

PubMed Central

Young, Li-Sen; Harrison, Benjamin R.; U.M., Narayana Murthy; Moffatt, Barbara A.; Gilroy, Simon; Masson, Patrick H.

2006-01-01

Adenosine kinase (ADK) is a key enzyme that regulates intra- and extracellular levels of adenosine, thereby modulating methyltransferase reactions, production of polyamines and secondary compounds, and cell signaling in animals. Unfortunately, little is known about ADK's contribution to the regulation of plant growth and development. Here, we show that ADK is a modulator of root cap morphogenesis and gravitropism. Upon gravistimulation, soluble ADK levels and activity increase in the root tip. Mutation in one of two Arabidopsis (Arabidopsis thaliana) ADK genes, ADK1, results in cap morphogenesis defects, along with alterations in root sensitivity to gravistimulation and slower kinetics of root gravitropic curvature. The kinetics defect can be partially rescued by adding spermine to the growth medium, whereas the defects in cap morphogenesis and gravitropic sensitivity cannot. The root morphogenesis and gravitropism defects of adk1-1 are accompanied by altered expression of the PIN3 auxin efflux facilitator in the cap and decreased expression of the auxin-responsive DR5-GUS reporter. Furthermore, PIN3 fails to relocalize to the bottom membrane of statocytes upon gravistimulation. Consequently, adk1-1 roots cannot develop a lateral auxin gradient across the cap, necessary for the curvature response. Interestingly, adk1-1 does not affect gravity-induced cytoplasmic alkalinization of the root statocytes, suggesting either that ADK1 functions between cytoplasmic alkalinization and PIN3 relocalization in a linear pathway or that the pH and PIN3-relocalization responses to gravistimulation belong to distinct branches of the pathway. Our data are consistent with a role for ADK and the S-adenosyl-l-methionine pathway in the control of root gravitropism and cap morphogenesis. PMID:16891550

A sensitive electrochemical aptasensor for multiplex antibiotics detection based on high-capacity magnetic hollow porous nanotracers coupling exonuclease-assisted cascade target recycling.

PubMed

Yan, Zhongdan; Gan, Ning; Li, Tianhua; Cao, Yuting; Chen, Yinji

2016-04-15

A multiplex electrochemical aptasensor was developed for simultaneous detection of two antibiotics such as chloramphenicol (CAP) and oxytetracycline (OTC), and high-capacity magnetic hollow porous nanotracers coupling exonuclease-assisted target recycling was used to improve sensitivity. The cascade amplification process consists of the exonuclease-assisted target recycling amplification and metal ions encoded magnetic hollow porous nanoparticles (MHPs) to produce voltammetry signals. Upon the specific recognition of aptamers to targets (CAP and OTC), exonuclease I (Exo I) selectively digested the aptamers which were bound with CAP and OTC, then the released CAP and OTC participated new cycling to produce more single DNA, which can act as trigger strands to hybrid with nanotracers to generate further signal amplification. MHPs were used as carriers to load more amounts of metal ions and coupling with Exo I assisted cascade target recycling can amplify the signal for about 12 folds compared with silica based nanotracers. Owing to the dual signal amplification, the linear range between signals and the concentrations of CAP and OTC were obtained in the range of 0.0005-50 ng mL(-1). The detection limits of CAP and OTC were 0.15 and 0.10 ng mL(-1) (S/N=3) which is more than 2 orders lower than commercial enzyme-linked immunosorbent immunoassay (ELISA) method, respectively. The proposed method was successfully applied to simultaneously detection of CAP and OTC in milk samples. Besides, this aptasensor can be applied to other antibiotics detection by changing the corresponding aptamer. The whole scheme is facile, selective and sensitive enough for antibiotics screening in food safety. Copyright © 2015 Elsevier B.V. All rights reserved.

The toxic effects of l-Cysteine-capped cadmium sulfide nanoparticles on the aquatic plant Spirodela polyrrhiza

NASA Astrophysics Data System (ADS)

Khataee, Alireza; Movafeghi, Ali; Nazari, Fatemeh; Vafaei, Fatemeh; Dadpour, Mohammad Reza; Hanifehpour, Younes; Joo, Sang Woo

2014-12-01

Plants play an important role in the fate of nanoparticles in the environment through their uptake, bioaccumulation, and transfer to trophic chains. However, the impacts of nanoparticles on plants as essential components of all ecosystems are not well documented. In the present study, the toxic effects of l-Cysteine-capped CdS nanoparticles on Spirodela polyrrhiza as an aquatic higher plant species were studied. l-Cysteine-capped CdS nanoparticles were synthesized using hydrothermal method and their characteristics were determined by XRD, SEM, HR-TEM, and FT-IR techniques. The diameter of majority of synthesized nanoparticles was about 15-20 nm. Subsequently, the uptake of l-Cysteine-capped CdS nanoparticles by the plant species was confirmed using epifluorescence microscopy. The activity of peroxidase and superoxide dismutase as antioxidant enzymes was assayed and the relative frond number was calculated in the presence of different concentrations of l-Cysteine-capped CdS nanoparticles. The obtained results revealed the toxic effects of the synthesized nanoparticles on S. polyrrhiza, leading to growth reduction and significant changes in antioxidant enzymes' activity.

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

Chauleau, Mathieu; Jacewicz, Agata; Shuman, Stewart

DNA 3' pp 5'G caps synthesized by the 3'-PO 4/5'-OH ligase RtcB have a strong impact on enzymatic reactions at DNA 3'-OH ends. Aprataxin, an enzyme that repairs A5'pp5'DNA ends formed during abortive ligation by classic 3'-OH/5'-PO 4 ligases, is also a DNA 3' de-capping enzyme, converting DNAppG to DNA 3'p and GMP. By taking advantage of RtcB's ability to utilize certain GTP analogs to synthesize DNAppN caps, we show that aprataxin hydrolyzes inosine and 6-O-methylguanosine caps, but is not adept at removing a deoxyguanosine cap. We report a 1.5 Å crystal structure of aprataxin in a complex with GMP,more » which reveals that: (i) GMP binds at the same position and in the same anti nucleoside conformation as AMP; and (ii) aprataxin makes more extensive nucleobase contacts with guanine than with adenine, via a hydrogen bonding network to the guanine O6, N1, N2 base edge. Alanine mutations of catalytic residues His147 and His149 abolish DNAppG de-capping activity, suggesting that the 3' de-guanylylation and 5' de-adenylylation reactions follow the same pathway of nucleotidyl transfer through a covalent aprataxin-(His147)–NMP intermediate. Alanine mutation of Asp63, which coordinates the guanosine ribose hydroxyls, impairs DNAppG de-capping.« less

CapZyme-Seq Comprehensively Defines Promoter-Sequence Determinants for RNA 5' Capping with NAD.

PubMed

Vvedenskaya, Irina O; Bird, Jeremy G; Zhang, Yuanchao; Zhang, Yu; Jiao, Xinfu; Barvík, Ivan; Krásný, Libor; Kiledjian, Megerditch; Taylor, Deanne M; Ebright, Richard H; Nickels, Bryce E

2018-05-03

Nucleoside-containing metabolites such as NAD + can be incorporated as 5' caps on RNA by serving as non-canonical initiating nucleotides (NCINs) for transcription initiation by RNA polymerase (RNAP). Here, we report CapZyme-seq, a high-throughput-sequencing method that employs NCIN-decapping enzymes NudC and Rai1 to detect and quantify NCIN-capped RNA. By combining CapZyme-seq with multiplexed transcriptomics, we determine efficiencies of NAD + capping by Escherichia coli RNAP for ∼16,000 promoter sequences. The results define preferred transcription start site (TSS) positions for NAD + capping and define a consensus promoter sequence for NAD + capping: HRRASWW (TSS underlined). By applying CapZyme-seq to E. coli total cellular RNA, we establish that sequence determinants for NCIN capping in vivo match the NAD + -capping consensus defined in vitro, and we identify and quantify NCIN-capped small RNAs (sRNAs). Our findings define the promoter-sequence determinants for NCIN capping with NAD + and provide a general method for analysis of NCIN capping in vitro and in vivo. Copyright © 2018 Elsevier Inc. All rights reserved.

Identification of functional domains in Arabidopsis thaliana mRNA decapping enzyme (AtDcp2)

PubMed Central

Gunawardana, Dilantha; Cheng, Heung-Chin; Gayler, Kenwyn R.

2008-01-01

The Arabidopsis thaliana decapping enzyme (AtDcp2) was characterized by bioinformatics analysis and by biochemical studies of the enzyme and mutants produced by recombinant expression. Three functionally significant regions were detected: (i) a highly disordered C-terminal region with a putative PSD-95, Discs-large, ZO-1 (PDZ) domain-binding motif, (ii) a conserved Nudix box constituting the putative active site and (iii) a putative RNA binding domain consisting of the conserved Box B and a preceding loop region. Mutation of the putative PDZ domain-binding motif improved the stability of recombinant AtDcp2 and secondary mutants expressed in Escherichia coli. Such recombinant AtDcp2 specifically hydrolysed capped mRNA to produce 7-methyl GDP and decapped RNA. AtDcp2 activity was Mn2+- or Mg2+-dependent and was inhibited by the product 7-methyl GDP. Mutation of the conserved glutamate-154 and glutamate-158 in the Nudix box reduced AtDcp2 activity up to 400-fold and showed that AtDcp2 employs the catalytic mechanism conserved amongst Nudix hydrolases. Unlike many Nudix hydrolases, AtDcp2 is refractory to inhibition by fluoride ions. Decapping was dependent on binding to the mRNA moiety rather than to the 7-methyl diguanosine triphosphate cap of the substrate. Mutational analysis of the putative RNA-binding domain confirmed the functional significance of an 11-residue loop region and the conserved Box B. PMID:18025047

Role of Surface-Capping Ligands in Photoexcited Electron Transfer between CdS Nanorods and [FeFe] Hydrogenase and the Subsequent H 2 Generation

DOE PAGES

Wilker, Molly B.; Utterback, James K.; Greene, Sophie; ...

2017-12-08

Complexes of CdS nanorods and [FeFe] hydrogenase from Clostridium acetobutylicum have been shown to photochemically produce H 2. This study examines the role of the ligands that passivate the nanocrystal surfaces in the electron transfer from photoexcited CdS to hydrogenase and the H 2 generation that follows. We functionalized CdS nanorods with a series of mercaptocarboxylate surface-capping ligands of varying lengths and measured their photoexcited electron relaxation by transient absorption (TA) spectroscopy before and after hydrogenase adsorption. Rate constants for electron transfer from the nanocrystals to the enzyme, extracted by modeling of TA kinetics, decrease exponentially with ligand length, suggestingmore » that the ligand layer acts as a barrier to charge transfer and controls the degree of electronic coupling. Relative light-driven H 2 production efficiencies follow the relative quantum efficiencies of electron transfer, revealing the critical role of surface-capping ligands in determining the photochemical activity of these nanocrystal-enzyme complexes. Our results suggest that the H 2 production in this system could be maximized with a choice of a surface-capping ligand that decreases the distance between the nanocrystal surface and the electron injection site of the enzyme.« less

Role of Surface-Capping Ligands in Photoexcited Electron Transfer between CdS Nanorods and [FeFe] Hydrogenase and the Subsequent H 2 Generation

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

Wilker, Molly B.; Utterback, James K.; Greene, Sophie

Complexes of CdS nanorods and [FeFe] hydrogenase from Clostridium acetobutylicum have been shown to photochemically produce H 2. This study examines the role of the ligands that passivate the nanocrystal surfaces in the electron transfer from photoexcited CdS to hydrogenase and the H 2 generation that follows. We functionalized CdS nanorods with a series of mercaptocarboxylate surface-capping ligands of varying lengths and measured their photoexcited electron relaxation by transient absorption (TA) spectroscopy before and after hydrogenase adsorption. Rate constants for electron transfer from the nanocrystals to the enzyme, extracted by modeling of TA kinetics, decrease exponentially with ligand length, suggestingmore » that the ligand layer acts as a barrier to charge transfer and controls the degree of electronic coupling. Relative light-driven H 2 production efficiencies follow the relative quantum efficiencies of electron transfer, revealing the critical role of surface-capping ligands in determining the photochemical activity of these nanocrystal-enzyme complexes. Our results suggest that the H 2 production in this system could be maximized with a choice of a surface-capping ligand that decreases the distance between the nanocrystal surface and the electron injection site of the enzyme.« less

Two-state dynamics of the SH3–SH2 tandem of Abl kinase and the allosteric role of the N-cap

PubMed Central

Corbi-Verge, Carles; Marinelli, Fabrizio; Zafra-Ruano, Ana; Ruiz-Sanz, Javier; Luque, Irene; Faraldo-Gómez, José D.

2013-01-01

The regulation and localization of signaling enzymes is often mediated by accessory modular domains, which frequently function in tandems. The ability of these tandems to adopt multiple conformations is as important for proper regulation as the individual domain specificity. A paradigmatic example is Abl, a ubiquitous tyrosine kinase of significant pharmacological interest. SH3 and SH2 domains inhibit Abl by assembling onto the catalytic domain, allosterically clamping it in an inactive state. We investigate the dynamics of this SH3–SH2 tandem, using microsecond all-atom simulations and differential scanning calorimetry. Our results indicate that the Abl tandem is a two-state switch, alternating between the conformation observed in the structure of the autoinhibited enzyme and another configuration that is consistent with existing scattering data for an activated form. Intriguingly, we find that the latter is the most probable when the tandem is disengaged from the catalytic domain. Nevertheless, an amino acid stretch preceding the SH3 domain, the so-called N-cap, reshapes the free-energy landscape of the tandem and favors the interaction of this domain with the SH2-kinase linker, an intermediate step necessary for assembly of the autoinhibited complex. This allosteric effect arises from interactions between N-cap and the SH2 domain and SH3–SH2 connector, which involve a phosphorylation site. We also show that the SH3–SH2 connector plays a determinant role in the assembly equilibrium of Abl, because mutations thereof hinder the engagement of the SH2-kinase linker. These results provide a thermodynamic rationale for the involvement of N-cap and SH3–SH2 connector in Abl regulation and expand our understanding of the principles of modular domain organization. PMID:23959873

Development of an ELISA assay for screening inhibitors against divalent metal ion dependent alphavirus capping enzyme.

PubMed

Kaur, Ramanjit; Mudgal, Rajat; Narwal, Manju; Tomar, Shailly

2018-06-26

Alphavirus non-structural protein, nsP1 has a distinct molecular mechanism of capping the viral RNAs than the conventional capping mechanism of host. Thus, alphavirus capping enzyme nsP1 is a potential drug target. nsP1 catalyzes the methylation of guanosine triphosphate (GTP) by transferring the methyl group from S-adenosylmethionine (SAM) to a GTP molecule at its N7 position with the help of nsP1 methyltransferase (MTase) followed by guanylylation (GT) reaction which involves the formation of m 7 GMP-nsP1 covalent complex by nsP1 guanylyltransferase (GTase). In subsequent reactions, m 7 GMP moiety is added to the 5' end of the viral ppRNA by nsP1 GTase resulting in the formation of cap0 structure. In the present study, chikungunya virus (CHIKV) nsP1 MTase and GT reactions were confirmed by an indirect non-radioactive colorimetric assay and western blot assay using an antibody specific for the m 7 G cap, respectively. The purified recombinant CHIKV nsP1 has been used for the development of a rapid and sensitive non-radioactive enzyme linked immunosorbent assay (ELISA) to identify the inhibitors of CHIKV nsP1. The MTase reaction is followed by GT reaction and resulted in m 7 GMP-nsP1 covalent complex formation. The developed ELISA nsP1 assay measures this m 7 GMP-nsP1 complex by utilizing anti-m 7 G cap monoclonal antibody. The mutation of a conserved residue Asp63 to Ala revealed its role in nsP1 enzyme reaction. Inductively coupled plasma mass spectroscopy (ICP-MS) was used to determine the presence of magnesium ions (Mg 2+ ) in the purified nsP1 protein. The divalent metal ion selectivity and investigation show preference for Mg 2+ ion by CHIKV nsP1. Additionally, using the developed ELISA nsP1 assay, the inhibitory effects of sinefungin, aurintricarboxylic acid (ATA) and ribavirin were determined and the IC 50 values were estimated to be 2.69 µM, 5.72 µM and 1.18 mM, respectively. Copyright © 2018. Published by Elsevier B.V.

Effects of combined neutral endopeptidase 24-11 and angiotensin-converting enzyme inhibition on femoral vascular conductance in streptozotocin-induced diabetic rats

PubMed Central

Arbin, V; Claperon, N; Fournié-Zaluski, M -C; Roques, B P; Peyroux, J

2000-01-01

The successive effects of the angiotensin-converting enzyme inhibitor captopril (CAP, 2 mg kg−1+1 mg kg−1 30 min−1 infusion) and the neutral endopeptidase 24-11 inhibitor retrothiorphan (RT, 25 mg kg−1+12.5 mg kg−1 30 min−1 infusion) were studied on femoral vascular conductance (FVC) in streptozotocin-induced diabetic (STZ-SD) and control Sprague-Dawley (C-SD) rats. The role of the kinin-nitric oxide (NO) pathway was assessed by (1) using pre-treatments: a bradykinin (BK) B2 receptor antagonist (Hoe-140, 300 μg kg−1), a NO-synthase inhibitor (Nω-nitro-L-arginine methyl ester, L-NAME, 10 mg kg−1), a kininase I inhibitor (DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid, MGTA, 10 mg kg−1+20 mg kg−1 20 min−1 infusion) and (2) comparing the effects in STZ-induced diabetic (STZ-BN) and control Brown-Norway kininogen-deficient (C-BN) rats.In C-SDs, CAP and CAP+RT increased FVC similarly. In STZ-SDs, FVC and FBF were decreased compared to C-SDs. CAP+RT increased them more effectively than CAP alone.In both C-SDs and STZ-SDs, the femoral bed vasodilatation elicited by CAP was inhibited by Hoe-140 and L-NAME. The FVC increase elicited by CAP+RT was not significantly reduced by Hoe-140 but was inhibited by L-NAME and Hoe-140+MGTA.In C-BNs, the vasodilatator responses to CAP and CAP+RT were abolished and highly reduced, respectively. In STZ-BNs, these responses were abolished.These results show that in STZ-SDs, CAP+RT improve FBF and FVC more effectively than CAP alone. These effects are linked to an increased activation of the kinin-NO pathway. BK could lead to NO production by BK B2 receptor activation and another pathway in which kininase I may be involved. PMID:10903969

African Swine Fever Virus NP868R Capping Enzyme Promotes Reovirus Rescue during Reverse Genetics by Promoting Reovirus Protein Expression, Virion Assembly, and RNA Incorporation into Infectious Virions

PubMed Central

Eaton, Heather E.; Kobayashi, Takeshi; Dermody, Terence S.; Johnston, Randal N.

2017-01-01

ABSTRACT Reoviruses, like many eukaryotic viruses, contain an inverted 7-methylguanosine (m7G) cap linked to the 5′ nucleotide of mRNA. The traditional functions of capping are to promote mRNA stability, protein translation, and concealment from cellular proteins that recognize foreign RNA. To address the role of mRNA capping during reovirus replication, we assessed the benefits of adding the African swine fever virus NP868R capping enzyme during reovirus rescue. C3P3, a fusion protein containing T7 RNA polymerase and NP868R, was found to increase protein expression 5- to 10-fold compared to T7 RNA polymerase alone while enhancing reovirus rescue from the current reverse genetics system by 100-fold. Surprisingly, RNA stability was not increased by C3P3, suggesting a direct effect on protein translation. A time course analysis revealed that C3P3 increased protein synthesis within the first 2 days of a reverse genetics transfection. This analysis also revealed that C3P3 enhanced processing of outer capsid μ1 protein to μ1C, a previously described hallmark of reovirus assembly. Finally, to determine the rate of infectious-RNA incorporation into new virions, we developed a new recombinant reovirus S1 gene that expressed the fluorescent protein UnaG. Following transfection of cells with UnaG and infection with wild-type virus, passage of UnaG through progeny was significantly enhanced by C3P3. These data suggest that capping provides nontraditional functions to reovirus, such as promoting assembly and infectious-RNA incorporation. IMPORTANCE Our findings expand our understanding of how viruses utilize capping, suggesting that capping provides nontraditional functions to reovirus, such as promoting assembly and infectious-RNA incorporation, in addition to enhancing protein translation. Beyond providing mechanistic insight into reovirus replication, our findings also show that reovirus reverse genetics rescue is enhanced 100-fold by the NP868R capping enzyme. Since reovirus shows promise as a cancer therapy, efficient reovirus reverse genetics rescue will accelerate production of recombinant reoviruses as candidates to enhance therapeutic potency. NP868R-assisted reovirus rescue will also expedite production of recombinant reovirus for mechanistic insights into reovirus protein function and structure. PMID:28298603

A Reaction Path Study of the Catalysis and Inhibition of the Bacillus anthracis CapD gamma-Glutamyl Transpeptidase

DTIC Science & Technology

2014-10-21

lases.11,30,31 The first bound structure of CapD [Protein Data Bank ( PDB ) entry 3G9K] was determined with a di-α-L-Glu ligand.29 The di-α-L-Glu ligand...Article dx.doi.org/10.1021/bi500623c | Biochemistry 2014, 53, 6954−69676956 into the CapD structure ( PDB entry 3G9K29) identified two principal...in capsule anchoring and remodeling makes the enzyme a promising target for anthrax medical countermeasures. Although the structure of CapD is known

Evidence for concerted kinetic oxidation of progesterone by purified rat hepatic cytochrome P-450g

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

Swinney, D.C.; Ryan, D.E.; Thomas, P.E.

1988-07-26

Purified cytochrome P-450g, a male-specific rat hepatic isozyme, was observed to metabolize progesterone to two primary metabolites (6..beta..-hydroxyprogesterone and 16..cap alpha..-hydroxyprogesterone), two secondary metabolites (6..beta..,16..cap alpha..-dihydroxyprogesterone and 6-ketoprogesterone), and one tertiary metabolite (6-keto-16..cap alpha..-hydroxyprogesterone). The K/sub m,app/ for the formation of these products from progesterone was determined to be approximately 0.5 ..mu..M, while the K/sub m,app/ for metabolism of 6..beta..- and 16..cap alpha..-hydroxyprogesterone was found to be 5-10 ..mu..M. The ratio of primary to secondary metabolites did not change significantly at progesterone concentrations from 6 to 150 ..mu..M, and a lag in formation of secondary metabolites was not observed inmore » 1-min incubations. Concerted oxidation of progesterone to secondary products without the intermediate products leaving the active site was suggested by these results and confirmed by isotopic dilution experiments in which little or no dilution of metabolically formed 6..beta..,16..cap alpha..-dihydroxyprogesterone and 6-keto-16..cap alpha..-hydroxyprogesterone was observed in incubations containing a mixture of radiolabeled progesterone and unlabeled 6..beta..-hydroxyprogesterone or 16..cap alpha..-hydroxyprogesterone. Incubation of 6..beta..-hydroxyprogesterone with a reconstituted system in an atmosphere of /sup 18/I/sub 2/ resulted in > 90% incorporation of /sup 18/O in the 16..cap alpha..-position of 6..beta..,16..cap alpha..-dihydroxyprogesterone but no incorporation of /sup 18/O into 6-ketoprogesterone, even though the reaction was dependent upon enzyme and O/sub 2/, and not inhibited by mannitol, catalase, or superoxide dismutase. Factors which characterize the metabolism of progesterone by cytochrome P-450g in terms of active-site constraints and the catalytic competence of the enzyme in microsomes were also explored.« less

[Cytochemical localization and properties of selected nucleolytic enzymes].

PubMed

Sierakowska, Halina

2015-01-01

In the article there are shortly outlined studies on cytochemical localization of selected nucleolytic enzymes carried out between 1957-1986 by David Shugar and his coworkers. The histochemical localization of several nucleolytic enzymes in animal and plant tissues was determined by synthesis of specific substrates, alpha-naphthyl esters of 5'- and 3'-nucleotides and their derivatives. In rat tissues phosphodiesterase I was localized in the plasma membrane whereas phosphodiesterase II in the lizosomes, reflecting their physiological roles. The localization of pancreatic type ribonuclease in animal tissues was determined, indicating its role in extracellular digestion. Plant nucleotide pyrophosphatase was localized in several tissues, purified to near homogeneity from potato tubers and its properties and substrate specificity were determined. Application of this enzyme for removal of m7GMP from the "cap" of eukaryotic mRNA allowed to elucidate the role of "cap" in mRNA binding to ribosomes in the process of translation. Furthermore, cyclic nucleotide phosphodiesterase was isolated from potato tubers and its physicochemical properties, oligomeric structure and substrate specificity were elucidated.

Neural and receptor cochlear potentials obtained by transtympanic electrocochleography in auditory neuropathy.

PubMed

Santarelli, Rosamaria; Starr, Arnold; Michalewski, Henry J; Arslan, Edoardo

2008-05-01

Transtympanic electrocochleography (ECochG) was recorded bilaterally in children and adults with auditory neuropathy (AN) to evaluate receptor and neural generators. Test stimuli were clicks from 60 to 120dB p.e. SPL. Measures obtained from eight AN subjects were compared to 16 normally hearing children. Receptor cochlear microphonics (CMs) in AN were of normal or enhanced amplitude. Neural compound action potentials (CAPs) and receptor summating potentials (SPs) were identified in five AN ears. ECochG potentials in those ears without CAPs were of negative polarity and of normal or prolonged duration. We used adaptation to rapid stimulus rates to distinguish whether the generators of the negative potentials were of neural or receptor origin. Adaptation in controls resulted in amplitude reduction of CAP twice that of SP without affecting the duration of ECochG potentials. In seven AN ears without CAP and with prolonged negative potential, adaptation was accompanied by reduction of both amplitude and duration of the negative potential to control values consistent with neural generation. In four ears without CAP and with normal duration potentials, adaptation was without effect consistent with receptor generation. In five AN ears with CAP, there was reduction in amplitude of CAP and SP as controls but with a significant decrease in response duration. Three patterns of cochlear potentials were identified in AN: (1) presence of receptor SP without CAP consistent with pre-synaptic disorder of inner hair cells; (2) presence of both SP and CAP consistent with post-synaptic disorder of proximal auditory nerve; (3) presence of prolonged neural potentials without a CAP consistent with post-synaptic disorder of nerve terminals. Cochlear potential measures may identify pre- and post-synaptic disorders of inner hair cells and auditory nerves in AN.

Comparison of immunoglobulin E measurements on IMMULITE and ImmunoCAP in samples consisting of allergen-specific mouse-human chimeric monoclonal antibodies towards allergen extracts and four recombinant allergens.

PubMed

Szecsi, Pal B; Stender, Steen

2013-01-01

Specific immunoglobulin E (IgE) antibody in vitro tests are performed on enzyme immunoassay systems. Poor agreement among systems has been reported and comparisons have been made exclusively with allergen extracts - not with recombinant allergens. Here we compare the ImmunoCAP and the IMMULITE systems. Ten patient samples with positive IgE toward egg white, birch pollen or cat or dog dander were compared using allergen extracts or the recombinant allergens Gal d 1, Bet v 1, Fel d 1 and Can f 1 with the two assay systems. Comparisons were also performed using four monoclonal mouse-human chimeric IgE antibodies specific for the same allergenic components. IMMULITE estimated a higher allergen-specific IgE concentration in sera than ImmunoCAP when testing with allergen extracts as well as recombinant allergens. The chimeric antibodies gave an equivalent response in the total IgE and specific IgE (sIgE) with an average ratio of 1.08 (range 0.9-1.3) on ImmunoCAP. In contrast, IMMULITE exhibited sIgE signals that were substantially higher than the summed level of IgE for all four chimeric antibodies (average ratio 2.96 and range 1.7-4.3). Comparison using chimeric antibodies allowed the evaluation of the true performance of the systems. ImmunoCAP measured total IgE and sIgE equally, whereas IMMULITE displayed higher sIgE signals when compared to the summed level of total IgE for all four chimeric antibodies. Results obtained with the two assay systems are not interchangeable by means of mathematical conversion. Copyright © 2013 S. Karger AG, Basel.

Development and application of an indirect enzyme-linked immunosorbent assay using recombinant truncated Cap protein for the diagnosis of porcine circovirus-like virus P1.

PubMed

Wen, Li-bin; Wen, Shi-fu; He, Kong-wang

2016-01-19

Porcine circovirus-like virus P1 is a newly discovered virus. To date, there has been no specific serological assay for use in the diagnosis of P1 infection. Because P1 has high homology to porcine circovirus type 2 (PCV2) at the nucleotide level, the C-terminal portion of the capsid protein (amino acids 73-114), a discriminative antigen, was expressed in a prokaryotic expression system. The recombinant product (rctCap), composed of three identical repeated domains, was shown to be strongly immunoreactive to P1-specific serum. This assay was validated by comparison with an indirect immunofluorescence assay (IFA). The diagnostic sensitivity and specificity of the rctCap enzyme-linked immunosorbent assay (ELISA) developed in this study are 93.6% and 98.3%, respectively, compared with the results from IFAs on 450 sera samples from pigs. The indirect ELISA that we developed with rctCap, the recombinant capsid fragment containing the 217-342 nt repeat domain, was sensitive, specific, and suitable for the large-scale detection of P1 infections in swine.

Design of enzyme-mediated controlled release systems based on silica mesoporous supports capped with ester-glycol groups.

PubMed

Agostini, Alessandro; Mondragón, Laura; Pascual, Lluis; Aznar, Elena; Coll, Carmen; Martínez-Máñez, Ramón; Sancenón, Félix; Soto, Juan; Marcos, M Dolores; Amorós, Pedro; Costero, Ana M; Parra, Margarita; Gil, Salvador

2012-10-16

An ethylene glycol-capped hybrid material for the controlled release of molecules in the presence of esterase enzyme has been prepared. The final organic-inorganic hybrid solid S1 was synthesized by a two-step procedure. In the first step, the pores of an inorganic MCM-41 support (in the form of nanoparticles) were loaded with [Ru(bipy)(3)]Cl(2) complex, and then, in the second step, the pore outlets were functionalized with ester glycol moieties that acted as molecular caps. In the absence of an enzyme, release of the complex from aqueous suspensions of S1 at pH 8.0 is inhibited due to the steric hindrance imposed by the bulky ester glycol moieties. Upon addition of esterase enzyme, delivery of the ruthenium complex was observed due to enzymatic hydrolysis of the ester bond in the anchored ester glycol derivative, inducing the release of oligo(ethylene glycol) fragments. Hydrolysis of the ester bond results in size reduction of the appended group, therefore allowing delivery of the entrapped cargo. The S1 nanoparticles were not toxic for cells, as demonstrated by cell viability assays with HeLa and MCF-7 cell lines, and were found to be associated with lysosomes, as shown by confocal microscopy. However, when S1 nanoparticles were filled with the cytotoxic drug camptothecin (S1-CPT), S1-CPT-treated cells undergo cell death as a result of S1-CPT cell internalization and subsequent cellular enzyme-mediated hydrolysis and aperture of the molecular gate that induced the release of the camptothecin cargo. These findings point to a possible therapeutic application of these nanoparticles.

Boosting the oxidase mimicking activity of nanoceria by fluoride capping: rivaling protein enzymes and ultrasensitive F- detection

NASA Astrophysics Data System (ADS)

Liu, Biwu; Huang, Zhicheng; Liu, Juewen

2016-07-01

Nanomaterial-based enzyme mimics (nanozymes) are currently a new forefront of chemical research. However, the application of nanozymes is limited by their low catalytic activity and low turnover numbers. Cerium dioxide nanoparticles (nanoceria) are among the few with oxidase activity. Herein, we report an interesting finding addressing their limitations. The oxidase activity of nanoceria is improved by over 100-fold by fluoride capping, making it more close to real oxidases. The turnover number reached 700 in 15 min, drastically improved from ~15 turnovers for the naked particles. The mechanism is attributed to surface charge modulation and facilitated electron transfer by F- capping based on ζ-potential and free radical measurements. Ultrasensitive sensing of fluoride was achieved with a detection limit of 0.64 μM F- in water and in toothpastes, while no other tested anions can achieve the activity enhancement.Nanomaterial-based enzyme mimics (nanozymes) are currently a new forefront of chemical research. However, the application of nanozymes is limited by their low catalytic activity and low turnover numbers. Cerium dioxide nanoparticles (nanoceria) are among the few with oxidase activity. Herein, we report an interesting finding addressing their limitations. The oxidase activity of nanoceria is improved by over 100-fold by fluoride capping, making it more close to real oxidases. The turnover number reached 700 in 15 min, drastically improved from ~15 turnovers for the naked particles. The mechanism is attributed to surface charge modulation and facilitated electron transfer by F- capping based on ζ-potential and free radical measurements. Ultrasensitive sensing of fluoride was achieved with a detection limit of 0.64 μM F- in water and in toothpastes, while no other tested anions can achieve the activity enhancement. Electronic supplementary information (ESI) available: Methods, TMB oxidation kinetics and control experiments. See DOI: 10.1039/c6nr02730j

pH-dependent immobilization of urease on glutathione-capped gold nanoparticles.

PubMed

Garg, Seema; De, Arnab; Mozumdar, Subho

2015-05-01

Urease is a nickel-dependent metalloenzyme that catalyzes the hydrolysis of urea to form ammonia and carbon dioxide. Although the enzyme serves a significant role in several detoxification and analytical processes, its usability is restricted due to high cost, availability in small amounts, instability, and a limited possibility of economic recovery from a reaction mixture. Hence, there is a need to develop an efficient, simple, and reliable immobilization strategy for the enzyme. In this study, the carboxyl terminated surface of glutathione-capped gold nanoparticles have been utilized as a solid support for the covalent attachment of urease. The immobilization has been carried out at different pH conditions so as to elucidate its effect on the immobilization efficiency and enzyme bioactivity. The binding of the enzyme has been quantitatively and qualitatively analyzed through techniques like ultraviolet-visible spectroscopy, intrinsic steady state fluorescence, and circular dichorism. The bioactivity of the immobilized enzyme was investigated with respect to the native enzyme under different thermal conditions. Recyclability and shelf life studies of the immobilized enzyme have also been carried out. Results reveal that the immobilization is most effective at pH of 7.4 followed by that in an acidic medium and is least in alkaline environment. The immobilized enzyme also exhibits enhance activity in comparison to the native form at physiological temperature. The immobilized urease (on gold glutathione nanoconjugates surface) can be effectively employed for biosensor fabrication, immunoassays and as an in vivo diagnostic tool in the future. © 2014 Wiley Periodicals, Inc.

Flavivirus RNA cap methyltransferase: structure, function, and inhibition.

PubMed

Liu, Lihui; Dong, Hongping; Chen, Hui; Zhang, Jing; Ling, Hua; Li, Zhong; Shi, Pei-Yong; Li, Hongmin

2010-08-01

Many flaviviruses are significant human pathogens. The plus-strand RNA genome of a flavivirus contains a 5' terminal cap 1 structure (m(7)GpppAmG). The flavivirus encodes one methyltransferase (MTase), located at the N-terminal portion of the NS5 RNA-dependent RNA polymerase (RdRp). Here we review recent advances in our understanding of flaviviral capping machinery and the implications for drug development. The NS5 MTase catalyzes both guanine N7 and ribose 2'-OH methylations during viral cap formation. Representative flavivirus MTases, from dengue, yellow fever, and West Nile virus (WNV), sequentially generate GpppA → m(7)GpppA → m(7)GpppAm. Despite the existence of two distinct methylation activities, the crystal structures of flavivirus MTases showed a single binding site for S-adenosyl-L-methionine (SAM), the methyl donor. This finding indicates that the substrate GpppA-RNA must be repositioned to accept the N7 and 2'-O methyl groups from SAM during the sequential reactions. Further studies demonstrated that distinct RNA elements are required for the methylations of guanine N7 on the cap and of ribose 2'-OH on the first transcribed nucleotide. Mutant enzymes with different methylation defects can trans complement one another in vitro, demonstrating that separate molecules of the enzyme can independently catalyze the two cap methylations in vitro. In the context of the infectious virus, defects in both methylations, or a defect in the N7 methylation alone, are lethal to WNV. However, viruses defective solely in 2'-O methylation are attenuated and can protect mice from later wild-type WNV challenge. The results demonstrate that the N7 methylation activity is essential for the WNV life cycle and, thus, methyltransferase represents a novel and promising target for flavivirus therapy.

Analytical nanosphere sensors using quantum dot-enzyme conjugates for urea and creatinine.

PubMed

Ruedas-Rama, Maria J; Hall, Elizabeth A H

2010-11-01

An enzyme-linked analytical nanosphere sensor (ANSor) is described, responding to enzyme-substrate turnover in the vicinity of a quantum dot (QD) due to coimmobilized enzyme and pH sensitive ligand. QD capping by mercapto-alkanoic acids were rejected as a pH sensitive ligand, but with the use of a layer-by-layer assembly on mercaptopropionic capped QDs and an intermediate poly(allylamine hydrochloride) layer, anthraquinone sulfonate (calcium red, CaR) was introduced to modify the pKa in the immobilized system > 8. QD-CaR absorption shows spectral overlap with QD530 emission at all pHs and gives a complex pH dependent fluorescence resonance energy transfer (FRET) efficiency, due to excited state proton transfer (λ(ex) = 540 nm; λ(em) = 585 nm). In contrast QD615-CaR with spectral overlap between the QD and CaR gave a strong and reproducible pH response. QD-urease and QD-creatinine deiminase conjugates could be linked with pH changes produced by enzyme degradation of urea and creatinine, respectively. Close coupling between the pH sensitive QD and enzyme conjugate maximized signal compared with solution based assays: QD-urease and QD-CD bioconjugates were tested in model biological media (Dulbecco's modified Eagle's Medium and fetal calf serum) and in urine, showing a response in 3-4 min.

Preparation of biosensors by immobilization of polyphenol oxidase in conducting copolymers and their use in determination of phenolic compounds in red wine.

PubMed

Böyükbayram, A Elif; Kiralp, Senem; Toppare, Levent; Yağci, Yusuf

2006-10-01

Electrochemically produced graft copolymers of thiophene capped polytetrahydofuran (TPTHF1 and TPTHF2) and pyrrole were achieved by constant potential electrolysis using sodium dodecylsulfate (SDS) as the supporting electrolyte. Characterizations were based on Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Electrical conductivities were measured by the four-probe technique. Novel biosensors for phenolic compounds were constructed by immobilizing polyphenol oxidase (PPO) into conducting copolymers prepared by electropolymerization of pyrrole with thiophene capped polytetrahydrofuran. Kinetic parameters, maximum reaction rate (V(max)) and Michaelis-Menten constant (K(m)) and optimum conditions regarding temperature and pH were determined for the immobilized enzyme. Operational stability and shelf-life of the enzyme electrodes were investigated. Enzyme electrodes of polyphenol oxidase were used to determine the amount of phenolic compounds in two brands of Turkish red wines and found very useful owing to their high kinetic parameters and wide pH working range.

Clinical audit project in undergraduate medical education curriculum: an assessment validation study

PubMed Central

Steketee, Carole; Mak, Donna

2016-01-01

Objectives To evaluate the merit of the Clinical Audit Project (CAP) in an assessment program for undergraduate medical education using a systematic assessment validation framework. Methods A cross-sectional assessment validation study at one medical school in Western Australia, with retrospective qualitative analysis of the design, development, implementation and outcomes of the CAP, and quantitative analysis of assessment data from four cohorts of medical students (2011- 2014). Results The CAP is fit for purpose with clear external and internal alignment to expected medical graduate outcomes.  Substantive validity in students’ and examiners’ response processes is ensured through relevant methodological and cognitive processes. Multiple validity features are built-in to the design, planning and implementation process of the CAP.  There is evidence of high internal consistency reliability of CAP scores (Cronbach’s alpha > 0.8) and inter-examiner consistency reliability (intra-class correlation>0.7). Aggregation of CAP scores is psychometrically sound, with high internal consistency indicating one common underlying construct.  Significant but moderate correlations between CAP scores and scores from other assessment modalities indicate validity of extrapolation and alignment between the CAP and the overall target outcomes of medical graduates.  Standard setting, score equating and fair decision rules justify consequential validity of CAP scores interpretation and use. Conclusions This study provides evidence demonstrating that the CAP is a meaningful and valid component in the assessment program. This systematic framework of validation can be adopted for all levels of assessment in medical education, from individual assessment modality, to the validation of an assessment program as a whole.  PMID:27716612

Clinical audit project in undergraduate medical education curriculum: an assessment validation study.

PubMed

Tor, Elina; Steketee, Carole; Mak, Donna

2016-09-24

To evaluate the merit of the Clinical Audit Project (CAP) in an assessment program for undergraduate medical education using a systematic assessment validation framework. A cross-sectional assessment validation study at one medical school in Western Australia, with retrospective qualitative analysis of the design, development, implementation and outcomes of the CAP, and quantitative analysis of assessment data from four cohorts of medical students (2011- 2014). The CAP is fit for purpose with clear external and internal alignment to expected medical graduate outcomes.  Substantive validity in students' and examiners' response processes is ensured through relevant methodological and cognitive processes. Multiple validity features are built-in to the design, planning and implementation process of the CAP.  There is evidence of high internal consistency reliability of CAP scores (Cronbach's alpha > 0.8) and inter-examiner consistency reliability (intra-class correlation>0.7). Aggregation of CAP scores is psychometrically sound, with high internal consistency indicating one common underlying construct.  Significant but moderate correlations between CAP scores and scores from other assessment modalities indicate validity of extrapolation and alignment between the CAP and the overall target outcomes of medical graduates.  Standard setting, score equating and fair decision rules justify consequential validity of CAP scores interpretation and use. This study provides evidence demonstrating that the CAP is a meaningful and valid component in the assessment program. This systematic framework of validation can be adopted for all levels of assessment in medical education, from individual assessment modality, to the validation of an assessment program as a whole.

New candidate markers of head and neck squamous cell carcinoma progression

NASA Astrophysics Data System (ADS)

Kakurina, G. V.; Kolegova, E. S.; Cheremisina, O. V.; Kulbakin, D. E.; Choinzonov, E. L.

2017-09-01

The tumor progression in head and neck squamous cell carcinoma (HNSCC) is one of the main causes of high mortality of the patients with HNSCC. The tumor progression, particularly the metastasis, is characterized by the changes in the composition, functions and structure of different proteins. We have previously shown that serum of HNSCC patients contains the proteins which regulate various cellular processes—adenylyl cyclase associated protein 1 (CAP1), protein phosphatase 1 B (PPM1B), etc. The levels of CAP1 and PPM1B were determined using the enzyme immunoassay. The results of this study show that CAP1 and PPM1B take a part in the progression of HNSCC. The levels of CAP1 and PPM1B in the tumor and in morphologically normal tissue depended on the prevalence of the tumor process. The CAP1 and PPM1B levels were significantly higher in tumor tissue of the patients with regional metastasis. Our data allow assuming the potential possibility for predicting the outcome of the HNSCC measuring the level of tissue CAP1.

Effects of selenizing angelica polysaccharide and selenizing garlic polysaccharide on immune function of murine peritoneal macrophage.

PubMed

Gao, Zhenzhen; Liu, Kuanhui; Tian, Weijun; Wang, Hongchao; Liu, Zhenguang; Li, Youying; Li, Entao; Liu, Cui; Li, Xiuping; Hou, Ranran; Yue, Chanjuan; Wang, Deyun; Hu, Yuanliang

2015-07-01

The effects of two selenizing polysaccharides (sCAP2 and sGPS6) on immune function of murine peritoneal macrophages taking two non-selenizing polysaccharides (CAP and GPS) and modifier Na2SeO3 as control. In vitro test, the changes of selenizing polysaccharides, non-selenizing polysaccharides and Na2SeO3 on murine macrophages function were evaluated by phagocytosis and nitric oxide (NO) secretion tests. In vivo test, the mice were injected respectively with 0.2, 0.4 and 0.6 mg of sCAP2, sGPS6, CAP and GPS, or Na2SeO3 80 μg or normal saline 0.4 mL. The peritoneal macrophages were collected and cultured to determine the contents of TNF-α, IL-6 and IL-10 in supernatants by enzyme-linked immunosorbent assay. The results showed that sCAP2 and sGPS6 could significantly promote the phagocytosis and secretion of NO and three cytokines of macrophages in comparison with CAP and GPS. sCAP2 possessed the strongest activity. This indicates that selenylation modification can further improve the immune-enhancing activity of polysaccharide, and sCAP2 could be as a new immunopotentiator. Copyright © 2015 Elsevier B.V. All rights reserved.

Mechanism of the lysosomal membrane enzyme acetyl coenzyme A: alpha-glucosaminide N-acetyltransferase

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

Bame, K.J.

1986-01-01

Acetyl-CoA:..cap alpha..-glucosaminide N-acetyltransferase is a lysosomal membrane enzyme, deficient in the genetic disease Sanfilippo C syndrome. The enzyme catalyzes the transfer of an acetyl group from cytoplasmic acetyl-CoA to terminal ..cap alpha..-glucosamine residues of heparan sulfate within the organelle. The reaction mechanism was examined using high purified lysosomal membranes from rat liver and human fibroblasts. The N-acetyltransferase reaction is optimal above pH 5.5 and a 2-3 fold stimulation of activity is observed in the presence of 0.1% taurodeoxycholate. Double reciprocal analysis and product inhibition studies indicate that the enzyme works by a Di-Iso Ping Pong Bi Bi mechanism. The bindingmore » of acetyl-CoA to the enzyme is measured by exchange label from (/sup 3/H)CoA to acetyl-CoA, and is optimal at pH's above 7.0. The acetyl-enzyme intermediate is formed by incubating membranes with (/sup 3/H)acetyl-CoA. The acetyl group can be transferred to glucosamine, forming (/sup 3/H)N-acetylglucosamine; the transfer is optimal between pH 4 and 5. Lysosomal membranes from Sanfilippo C fibroblasts confirm that these half reactions carried out by the N-acetyltransferase. The enzyme is inactivated by N-bromosuccinimide and diethylpyrocarbonate, indicating that a histidine is involved in the reaction. These results suggest that the histidine residue is at the active site of the enzyme. The properties of the N-acetyltransferase in the membrane, the characterization of the enzyme kinetics, the chemistry of a histidine mediated acetylation and the pH difference across the lysosomal membrane all support a transmembrane acetylation mechanism.« less

SWSA 6 interim corrective measures environmental monitoring: FY 1991 results

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

Clapp, R.B.; Marshall, D.S.

1992-06-01

In 1988, interim corrective measures (ICMs) were implemented at Solid Waste Storage Area (SWSA) 6 at Oak Ridge National Laboratory. The SWSA 6 site was regulated under the Resource Conservation and Recovery Act (RCRA). The ICMs consist of eight large high-density polyethylene sheets placed as temporary caps to cover trenches known to contain RCRA-regulated materials. Environmental monitoring for FY 1991 consisted of collecting water levels at 13 groundwater wells outside the capped areas and 44 wells in or near the capped areas in order to identify any significant loss of hydrologic isolation of the wastes. Past annual reports show thatmore » the caps are only partially effective in keeping the waste trenches dry and that many trenches consistently or intermittently contain water.« less

SWSA 6 interim corrective measures environmental monitoring: FY 1991 results. Environmental Restoration Program

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

Clapp, R.B.; Marshall, D.S.

1992-06-01

In 1988, interim corrective measures (ICMs) were implemented at Solid Waste Storage Area (SWSA) 6 at Oak Ridge National Laboratory. The SWSA 6 site was regulated under the Resource Conservation and Recovery Act (RCRA). The ICMs consist of eight large high-density polyethylene sheets placed as temporary caps to cover trenches known to contain RCRA-regulated materials. Environmental monitoring for FY 1991 consisted of collecting water levels at 13 groundwater wells outside the capped areas and 44 wells in or near the capped areas in order to identify any significant loss of hydrologic isolation of the wastes. Past annual reports show thatmore » the caps are only partially effective in keeping the waste trenches dry and that many trenches consistently or intermittently contain water.« less

Generation of human induced pluripotent stem cells using non-synthetic mRNA.

PubMed

Rohani, L; Fabian, C; Holland, H; Naaldijk, Y; Dressel, R; Löffler-Wirth, H; Binder, H; Arnold, A; Stolzing, A

2016-05-01

Here we describe some of the crucial steps to generate induced pluripotent stem cells (iPSCs) using mRNA transfection. Our approach uses a V. virus-derived capping enzyme instead of a cap-analog, ensuring 100% proper cap orientation for in vitro transcribed mRNA. V. virus' 2'-O-Methyltransferase enzyme creates a cap1 structure found in higher eukaryotes and has higher translation efficiency compared to other methods. Use of the polymeric transfection reagent polyethylenimine proved superior to other transfection methods. The mRNA created via this method did not trigger an intracellular immune response via human IFN-gamma (hIFN-γ) or alpha (hIFN-α) release, thus circumventing the use of suppressors. Resulting mRNA and protein were expressed at high levels for over 48h, thus obviating daily transfections. Using this method, we demonstrated swift activation of pluripotency associated genes in human fibroblasts. Low oxygen conditions further facilitated colony formation. Differentiation into different germ layers was confirmed via teratoma assay. Reprogramming with non-synthetic mRNA holds great promise for safe generation of iPSCs of human origin. Using the protocols described herein we hope to make this method more accessible to other groups as a fast, inexpensive, and non-viral reprogramming approach. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Quantum Dot Nanotoxicity Investigations Using Human Lung Cells and TOXOR Electrochemical Enzyme Assay Methodology.

PubMed

O'Hara, Tony; Seddon, Brian; O'Connor, Andrew; McClean, Siobhán; Singh, Baljit; Iwuoha, Emmanuel; Fuku, Xolile; Dempsey, Eithne

2017-01-27

Recent studies have suggested that certain nanomaterials can interfere with optically based cytotoxicity assays resulting in underestimations of nanomaterial toxicity. As a result there has been growing interest in the use of whole cell electrochemical biosensors for nanotoxicity applications. Herein we report application of an electrochemical cytotoxicity assay developed in house (TOXOR) in the evaluation of toxic effects of mercaptosuccinic acid capped cadmium telluride quantum dots (MSA capped CdTe QDs), toward mammalian cells. MSA capped CdTe QDs were synthesized, characterized, and their cytotoxicity toward A549 human lung epithelial cells investigated. The internalization of QDs within cells was scrutinized via confocal microscopy. The cytotoxicity assay is based on the measurement of changes in cellular enzyme acid phosphatase upon 24 h exposure to QDs. Acid phosphatase catalyzes dephosphorylation of 2-naphthyl phosphate to 2-naphthol (determined by chronocoulometry) and is indicative of metabolic activity in cells. The 24 h IC50 (concentration resulting in 50% reduction in acid phosphatase activity) value for MSA capped CdTe QDs was found to be 118 ± 49 μg/mL using the TOXOR assay and was in agreement with the MTT assay (157 ± 31 μg/mL). Potential uses of this electrochemical assay include the screening of nanomaterials, environmental toxins, in addition to applications in the pharmaceutical, food, and health sectors.

Comparative study of two precision overdenture attachment designs.

PubMed

Cohen, B I; Pagnillo, M; Condos, S; Deutsch, A S

1996-08-01

In this study two precision overdenture attachment designs were tested for retention--a nylon overdenture cap system and a new cap and keeper system. The new cap and keeper system was designed to reduce the time involved in replacing a cap worn by the conditions of the oral environment. Six groups were tested at two different angles and retentive failure was examined at two different angles (26 and 0 degrees). Failure was measured in pounds with a force gauge over a 2000 pull cycle. The amount of force required to remove caps for two overdenture caps and a replaced cap for the metal keeper system was determined. Two dependent variables were absolute force and relative force. Repeated measures analysis of variance (RMANOVA) was used to compare the between-subjects effects of cap and angle, and the within-subjects effect of pull. The results indicated a significant difference between cap types (p < 0.0001) with respect to the relative force required to remove the cap. There was no effect of angle. For absolute force, RMANOVA revealed a highly significant interaction between pull and cap (p < 0.0001). Thus, the way that force changed over pulls depended on which cap was used (no effect of angle). For relative force, RMANOVA revealed no interaction between pull and cap, but there was a main effect of cap type (p < 0.0001) (no effect of angle). The nylon cap design required less force for removal but showed more consistency in the force required over the course of the 2000 pulls when compared with the keeper with cap insert. The results obtained in this study were consistent with similar studies in literature.

A large-scale field trial of thin-layer capping of PCDD/F-contaminated sediments: Sediment-to-water fluxes up to 5 years post-amendment.

PubMed

Cornelissen, Gerard; Schaanning, Morten; Gunnarsson, Jonas S; Eek, Espen

2016-04-01

The longer-term effect (3-5 y) of thin-layer capping on in situ sediment-to-surface water fluxes was monitored in a large-scale field experiment in the polychlorinated dibenzodioxin and dibenzofuran (PCDD/F) contaminated Grenlandfjords, Norway (4 trial plots of 10,000 to 40,000 m(2) at 30 to 100 m water depth). Active caps (designed thickness 2.5 cm) were established in 2 fjords, consisting of dredged clean clay amended with powdered activated carbon (PAC) from anthracite. These active caps were compared to 2 nonactive caps in one of the fjords (designed thickness 5 cm) consisting of either clay only (i.e., without PAC) or crushed limestone. Sediment-to-water PCDD/F fluxes were measured in situ using diffusion chambers. An earlier study showed that during the first 2 years after thin-layer capping, flux reductions relative to noncapped reference fields were more extensive at the fields capped with nonactive caps (70%-90%) than at the ones with PAC-containing caps (50%-60%). However, the present work shows that between 3 and 5 years after thin-layer capping, this trend was reversed and cap effectiveness in reducing fluxes was increasing to 80% to 90% for the PAC caps, whereas cap effectiveness of the nonactive caps decreased to 20% to 60%. The increasing effectiveness over time of PAC-containing "active" caps is explained by a combination of slow sediment-to-PAC mass transfer of PCDD/Fs and bioturbation by benthic organisms. The decreasing effectiveness of "nonactive" limestone and clay caps is explained by deposition of contaminated particles on top of the caps. The present field data indicate that the capping efficiency of thin active caps (i.e., enriched with PAC) can improve over time as a result of slow diffusive PCDD/F transfer from sediment to PAC particles and better mixing of the PAC by bioturbation. © 2015 SETAC.

Geochemical constraints on the origin of Doushantuo cap carbonates in the Yangtze Gorges area, South China

NASA Astrophysics Data System (ADS)

Wang, Qinxian; Lin, Zhijia; Chen, Duofu

2014-05-01

Marinoan cap carbonates have been suggested to be primarily deposited in glacial meltwater and upwelled seawater. However, elemental geochemistry evidence for this depositional model is lacking. Here, we report high-spatial-resolution measurements of major, trace and rare earth elements of the Doushantuo cap carbonates from the Jiulongwan section in the Yangtze Gorges area, South China. Our results show that: 1) the basal cap carbonates display slight MREE enrichment, weak positive La anomalies, near-chondritic Y/Ho ratios, and slight negative Ce anomalies; 2) the lower-middle cap carbonates show slight LREE depletion or MREE enrichment, weak positive La and Eu anomalies, supra-chondritic Y/Ho ratios, and slight negative Ce anomalies; 3) the upper-middle cap carbonates have consistent enrichment of P, Fe, and trace metals, slight LREE depletion, and weak positive Ce, La and Eu anomalies; and 4) the upper cap carbonates exhibit LREE enrichment, weak positive La and Eu anomalies, supra-chondritic Y/Ho ratios, and mild negative Ce anomalies. These findings indicate that the Doushantuo cap carbonates did not precipitate from normal contemporaneous seawater, rather, the basal cap carbonates were deposited in oxygenated, relatively pure deglacial meltwater; the lower-middle cap carbonates in oxygenated brackish water; the upper-middle cap carbonates in upwelled anoxic brine water; and the upper cap carbonates in oxygenated brackish water. Our depositional model is consistent with the proposed sequence of events after the meltdown of Marinoan glaciation by Shields (2005).

Synthesis and biological studies of highly concentrated lisinopril-capped gold nanoparticles for CT tracking of angiotensin converting enzyme (ACE)

NASA Astrophysics Data System (ADS)

Ghann, William E.; Aras, Omer; Fleiter, Thorsten; Daniel, Marie-Christine

2011-05-01

For patients with a history of heart attack or stroke, the prevention of another cardiovascular or cerebrovascular event is crucial. The development of cardiac and pulmonary fibrosis has been associated with overexpression of tissue angiotensin-converting enzyme (ACE). Recently, gold nanoparticles (GNPs) have shown great potential as X-ray computed tomography (CT) contrast agents. Since lisinopril is an ACE inhibitor, it has been used as coating on GNPs for targeted imaging of tissue ACE in prevention of fibrosis. Herein, lisinopril-capped gold nanoparticles (LIS-GNPs) were synthesized up to a concentration of 55 mgAu/mL. Their contrast was measured using CT and the results were compared to Omnipaque, a commonly used iodine-based contrast agent. The targeting ability of these LIS-GNPs was also assessed.

Exploring Step‐by‐Step Assembly of Nanoparticle:Cytochrome Biohybrid Photoanodes

PubMed Central

Hwang, Ee Taek; Orchard, Katherine L.; Hojo, Daisuke; Beton, Joseph; Lockwood, Colin W. J.; Adschiri, Tadafumi

2017-01-01

Abstract Coupling light‐harvesting semiconducting nanoparticles (NPs) with redox enzymes has been shown to create artificial photosynthetic systems that hold promise for the synthesis of solar fuels. High quantum yields require efficient electron transfer from the nanoparticle to the redox protein, a property that can be difficult to control. Here, we have compared binding and electron transfer between dye‐sensitized TiO2 nanocrystals or CdS quantum dots and two decaheme cytochromes on photoanodes. The effect of NP surface chemistry was assessed by preparing NPs capped with amine or carboxylic acid functionalities. For the TiO2 nanocrystals, binding to the cytochromes was optimal when capped with a carboxylic acid ligand, whereas for the CdS QDs, better adhesion was observed for amine capped ligand shells. When using TiO2 nanocrystals, dye‐sensitized with a phosphonated bipyridine Ru(II) dye, photocurrents are observed that are dependent on the redox state of the decaheme, confirming that electrons are transferred from the TiO2 nanocrystals to the surface via the decaheme conduit. In contrast, when CdS NPs are used, photocurrents are not dependent on the redox state of the decaheme, consistent with a model in which electron transfer from CdS to the photoanode bypasses the decaheme protein. These results illustrate that although the organic shell of NPs nanoparticles crucially affects coupling with proteinaceous material, the coupling can be difficult to predict or engineer. PMID:28920010

Racemization of alanine by the alanine racemases from Salmonella typhimurium and Bacillus stearothermophilus: energetic reaction profiles

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

Faraci, W.S.; Walsh, C.T.

1988-05-03

Alanine racemases are bacterial pyridoxal 5'-phosphate (PLP) dependent enzymes providing D-alanine as an essential building block for biosynthesis of the peptidoglycan layer of the cell wall. Two isozymic alanine racemases, encoded by the dadB gene and the alr gene, from the Gram-negative mesophilic Salmonella typhimurium and one from the Gram-positive thermophilic Bacillus stearothermophilus have been examined for the racemization mechanism. Substrate deuterium isotope effects and solvent deuterium isotope effects have been measured in both L ..-->.. D and D..-->.. L directions for all three enzymes to assess the degree to which abstraction of the ..cap alpha..-proton or protonation of substratemore » PLP carbanion is limiting in catalysis. Additionally, experiments measuring internal return of ..cap alpha..-/sup 3/H from substrate to product and solvent exchange/substrate conversion experiments in /sup 3/H/sub 2/O have been used with each enzyme to examine the partitioning of substrate PLP carbanion intermediates and to obtain the relative heights of kinetically significant energy barriers in alanine racemase catalysis.« less

CONSISTENT INFLAMMATORY RESPONSE FOLLOWING EXPOSURE TO CONCENTRATED AMBIENT PARTICLES (CAPS) DURING FALL SEASON IN WISTAR-KYOTO RATS

EPA Science Inventory

CONSISTENT INFLAMMATORY RESPONSE FOLLOWING EXPOSURE TO CONCENTRATED AMBIENT PARTICLES (CAPs) DURING FALL SEASON IN WISTAR-KYOTO RATS.
UP Kodavanti, MC Schladweiler, AD Ledbetter, LC Walsh, PS Gilmour, MI Gilmour, WP Watkinson, JP Nolan, JH Richards, D Andrews, DL Costa. US EPA...

New formulation of an old drug in hypertension treatment: the sustained release of captopril from cyclodextrin nanoparticles

PubMed Central

de Azevedo, Mariangela de Burgos M; Tasic, Ljubica; Fattori, Juliana; Rodrigues, Fábio HS; Cantos, Fabiana C; Ribeiro, Leandro P; de Paula, Vanice; Ianzer, Danielle; Santos, Robson AS

2011-01-01

Captopril (CAP) was the first angiotensin I-converting enzyme (ACE) inhibitor to be developed and is widely used in hypertension treatment. On the other hand, cyclodextrins (CDs) are cyclic oligosaccharides whose cone-shaped cavity allows formation of noncovalent inclusion complexes with appropriately sized guest molecules, thus modifying guest physical, chemical, and biological properties. Herein, the physicochemical characterization and in vivo ACE inhibition evaluation of seven CAP/CD complexes are reported. The inclusion complexes were prepared by spray-drying, freeze-drying, kneading, or lyophilization methods and characterized by nuclear magnetic resonance, Fourier-transformed infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy techniques. In vivo assays compared CAP and CAP/CD complex administration (0.5 mg kg−1 or 0.09 mg kg−1, n = 4–7) to evaluate the ACE inhibition by continuous infusion of angiotensin I (30 ng 50 μL−1 min−1) in conscious Wistar rats. The physicochemical analysis demonstrated complete amorphization and complexation between CAP and CDs, indicating the substitution of water molecules inside the CD cavity with CAP. During the infusion of angiotensin I, the administration of all CAP/CD complexes induced a reduction in mean arterial pressure similar to that observed upon CAP administration. The nanoparticles obtained by the kneading method (CAP/α-CD:KM) showed a potent and long-lasting inhibitory activity (∼22 hours) on the angiotensin I pressor effect. The results suggest that the inclusion complex of CAP and α-CD can function as a novel antihypertensive formulation that may improve therapeutic use of CAP by reducing its oral dose administration to once per day, thus providing better quality of life for almost 25% of the world’s population who suffer from hypertension. PMID:21720512

Toward the in vivo study of captopril-conjugated quantum dots

NASA Astrophysics Data System (ADS)

Manabe, Noriyoshi; Hoshino, Akiyoshi; Liang, Yi-qiang; Goto, Tomomasa; Kato, Norihiro; Yamamoto, Kenji

2005-04-01

Photo-luminescent semiconductor quantum dots are nanometer-size probes that have the potential to be applied to the fields of the bio-imaging and the study of the cell mobility inside the body. At the same time, on the other hand, quantum dots are expected to carry some kind of molecules to the local organ inside of the animal body, which leads to the expectation that they can be used as a medicine-carrier. For this purpose, we conjugate (2S)-1-[(2s)-2-Methyl-3-sulfanylpropionyl]pyrrolidine-2-carboxylic acid (cap) with the quantum dot. Cap has the effect as an anti-hypertension drug, which inhibits angiotensin 1 converting enzyme. We conjugated the quantum dot with cap by the exchange reaction avoiding the regions which holds medicinal effect. Quantum dot conjugated with cap (QD-cap) were 3-times brighter than thioglycerol-coated quantum dots (QD-OH). The particle size of cap was 1.1nm and that of QD-cap was 12nm. QD-cap was permeated into the HeLa cells, while QD-MUA were taken into the HeLa cells by endocytosis. In addition, no apoptosis was detected against the cells that permeated QD-cap, because there was no damage to DNA. These results indicated that QD-conjugated medicines (QD-medicine) could be safe in the experiment on the level of the cell. More over, when QD-cap was intravenously injected into Stroke-prone Spontaneously Hypertensive Rats (SHRSP), they reduced blood pressure at systole. Therefore, the anti-hypertension effect of cap remained after conjugated with the quantum dot. These results suggested that QD-medicine were effective on the animal level.

Ybp1 and Gpx3 signaling in Candida albicans govern hydrogen peroxide-induced oxidation of the Cap1 transcription factor and macrophage escape.

PubMed

Patterson, Miranda J; McKenzie, Christopher G; Smith, Deborah A; da Silva Dantas, Alessandra; Sherston, Sam; Veal, Elizabeth A; Morgan, Brian A; MacCallum, Donna M; Erwig, Lars-Peter; Quinn, Janet

2013-12-20

As Candida albicans is the major fungal pathogen of humans, there is an urgent need to understand how this pathogen evades toxic reactive oxygen species (ROS) generated by the host immune system. A key regulator of antioxidant gene expression, and thus ROS resistance, in C. albicans is the AP-1-like transcription factor Cap1. Despite this, little is known regarding the intracellular signaling mechanisms that underlie the oxidation and activation of Cap1. Therefore, the aims of this study were; (i) to identify the regulatory proteins that govern Cap1 oxidation, and (ii) to investigate the importance of Cap1 oxidation in C. albicans pathogenesis. In response to hydrogen peroxide (H2O2), but not glutathione-depleting/modifying oxidants, Cap1 oxidation, nuclear accumulation, phosphorylation, and Cap1-dependent gene expression, is mediated by a glutathione peroxidase-like enzyme, which we name Gpx3, and an orthologue of the Saccharomyces cerevisiae Yap1 binding protein, Ybp1. In addition, Ybp1 also functions to stabilise Cap1 and this novel function is conserved in S. cerevisiae. C. albicans cells lacking Cap1, Ybp1, or Gpx3, are unable to filament and thus, escape from murine macrophages after phagocytosis, and also display defective virulence in the Galleria mellonella infection model. Ybp1 is required to promote the stability of fungal AP-1-like transcription factors, and Ybp1 and Gpx3 mediated Cap1-dependent oxidative stress responses are essential for the effective killing of macrophages by C. albicans. Activation of Cap1, specifically by H2O2, is a prerequisite for the subsequent filamentation and escape of this fungal pathogen from the macrophage.

Incorporating spatial constraint in co-activation pattern analysis to explore the dynamics of resting-state networks: An application to Parkinson's disease.

PubMed

Zhuang, Xiaowei; Walsh, Ryan R; Sreenivasan, Karthik; Yang, Zhengshi; Mishra, Virendra; Cordes, Dietmar

2018-05-15

The dynamics of the brain's intrinsic networks have been recently studied using co-activation pattern (CAP) analysis. The CAP method relies on few model assumptions and CAP-based measurements provide quantitative information of network temporal dynamics. One limitation of existing CAP-related methods is that the computed CAPs share considerable spatial overlap that may or may not be functionally distinct relative to specific network dynamics. To more accurately describe network dynamics with spatially distinct CAPs, and to compare network dynamics between different populations, a novel data-driven CAP group analysis method is proposed in this study. In the proposed method, a dominant-CAP (d-CAP) set is synthesized across CAPs from multiple clustering runs for each group with the constraint of low spatial similarities among d-CAPs. Alternating d-CAPs with less overlapping spatial patterns can better capture overall network dynamics. The number of d-CAPs, the temporal fraction and spatial consistency of each d-CAP, and the subject-specific switching probability among all d-CAPs are then calculated for each group and used to compare network dynamics between groups. The spatial dissimilarities among d-CAPs computed with the proposed method were first demonstrated using simulated data. High consistency between simulated ground-truth and computed d-CAPs was achieved, and detailed comparisons between the proposed method and existing CAP-based methods were conducted using simulated data. In an effort to physiologically validate the proposed technique and investigate network dynamics in a relevant brain network disorder, the proposed method was then applied to data from the Parkinson's Progression Markers Initiative (PPMI) database to compare the network dynamics in Parkinson's disease (PD) and normal control (NC) groups. Fewer d-CAPs, skewed distribution of temporal fractions of d-CAPs, and reduced switching probabilities among final d-CAPs were found in most networks in the PD group, as compared to the NC group. Furthermore, an overall negative association between switching probability among d-CAPs and disease severity was observed in most networks in the PD group as well. These results expand upon previous findings from in vivo electrophysiological recording studies in PD. Importantly, this novel analysis also demonstrates that changes in network dynamics can be measured using resting-state fMRI data from subjects with early stage PD. Copyright © 2018 Elsevier Inc. All rights reserved.

Triton Southern Hemisphere

NASA Image and Video Library

1998-06-08

This polar projection from NASA Voyager 2 of Triton southern hemisphere provides a view of the southern polar cap and bright equatorial fringe. The margin of the cap is scalloped and ranges in latitude from +10 degrees to -30 degrees. The bright fringe is closely associated with the cap's margin; from it, diffuse bright rays extend north-northeast for hundreds of kilometers. The bright fringe probably consists of very fresh nitrogen frost or snow, and the rays consist of bright-fringe materials that were redistributed by north-moving Coriolis-deflected winds. http://photojournal.jpl.nasa.gov/catalog/PIA00423

Serum-deprivation stimulates cap-binding by PARN at the expense of eIF4E, consistent with the observed decrease in mRNA stability

PubMed Central

Seal, Ruth; Temperley, Richard; Wilusz, Jeffrey; Lightowlers, Robert N.; Chrzanowska-Lightowlers, Zofia M. A.

2005-01-01

PARN, a poly(A)-specific ribonuclease, binds the 5′ cap-structure of mRNA and initiates deadenylation-dependent decay. Eukaryotic initiation factor 4E (eIF4E) also binds to the cap structure, an interaction that is critical for initiating cap-dependent translation. The stability of various mRNA transcripts in human cell lines is reduced under conditions of serum starvation as determined by both functional and chemical half-lives. Serum starvation also leads to enhanced cap association by PARN. In contrast, the 5′ cap occupancy by eIF4E decreases under serum-deprivation, as does the translation of reporter transcripts. Further, we show that PARN is a phosphoprotein and that this modification can be modulated by serum status. Taken together, these data are consistent with a natural competition existing at the 5′ cap structure between PARN and eIF4E that may be regulated by changes in post-translational modifications. These phosphorylation-induced changes in the interplay of PARN and eIF4E may determine whether the mRNA is translated or decayed. PMID:15653638

Plasma levels of soluble intercellular adhesion molecule-1 as a biomarker for disease severity of patients with community-acquired pneumonia.

PubMed

Chang, Pin-Yu; Tsao, Shih-Ming; Chang, Jer-Hwa; Chien, Ming-Hsien; Hung, Wen-Yueh; Huang, Yi-Wen; Yang, Shun-Fa

2016-12-01

Community-acquired pneumonia (CAP) is characterized as an acute inflammation of the lung associated with the activation of macrophages and neutrophils. Intercellular adhesion molecule-1 (ICAM-1) is an essential adhesion molecule involved in immune cell recruitment in lung inflammation. We investigated whether ICAM-1 is a useful biomarker for assessing the disease severity of hospitalized adult patients with CAP. Plasma soluble ICAM-1 (sICAM-1) levels were measured in 78 patients with CAP and 69 healthy controls by using a commercial enzyme-linked immunosorbent assay. The pneumonia severity index scores were used to determine CAP severity in patients upon initial hospitalization. The sICAM-1 and C-reactive protein (CRP) levels decreased significantly in patients with CAP after antibiotic treatment. The plasma concentration of sICAM-1 alone, but not CRP, was correlated with CAP severity according to the pneumonia severity index scores (r=0.431, p<0.001). The sICAM-1 levels in patients with CAP with high mortality risk were significantly higher than those in patients with CAP with medium or low mortality risk. Moreover, the sICAM-1 level showed a significant correlation with the length of hospital stay (r=0.488, p<0.001). Mechanistic investigations found that bacterial lipopolysaccharide induced upregulation of ICAM-1 expression through the c-Jun N-terminal kinase pathway in RAW264.7 macrophages. Plasma sICAM-1 levels may play a role in the diagnosis and clinical assessment of CAP severity. Copyright © 2016 Elsevier B.V. All rights reserved.

Capsaicinoids improve consequences of physical activity.

PubMed

Sahin, Kazim; Orhan, Cemal; Tuzcu, Mehmet; Sahin, Nurhan; Erten, Fusun; Juturu, Vijaya

2018-01-01

The purpose of this study was to investigate the effects of capsaicinoids (CAPs) on lipid metabolism, inflammation, antioxidant status and the changes in gene products involved in these metabolic functions in exercised rats. A total of 28 male Wistar albino rats were randomly divided into four groups (n = 7) (i) No exercise and no CAPs, (ii) No exercise + CAPs (iii) Regular exercise, (iv) Regular exercise + CAPs. Rats were administered as 0.2 mg capsaicinoids from 10 mg/kg BW/day Capsimax ® daily for 8 weeks. A significant decrease in lactate and malondialdehyde (MDA) levels and increase in activities of antioxidant enzymes were observed in the combination of regular exercise and CAPs group ( P < 0.0001). Regular exercise + CAPs treated rats had greater nuclear factor-E2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) levels in muscle than regular exercise and no exercise rats ( P < 0.001). Nevertheless, regular exercise + CAPs treated had lower nuclear factor kappa B (NF-κB) and IL-10 levels in muscle than regular exercise and control rats ( P < 0.001). Muscle sterol regulatory element-binding protein 1c (SREBP-1c), liver X receptors (LXR), ATP citrate lyase (ACLY) and fatty acid synthase (FAS) levels in the regular exercise + CAPs group were lower than all groups ( P < 0.05). However, muscle PPAR-γ level was higher in the regular exercise and CAPs alone than the no exercise rats. These results suggest CAPs with regular exercise may enhance lipid metabolism by regulation of gene products involved in lipid and antioxidant metabolism including SREBP-1c, PPAR-γ, and Nrf2 pathways in rats.

DEAD ZONE IN THE POLAR-CAP ACCELERATOR OF PULSARS

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

Chen, Alexander Y.; Beloborodov, Andrei M.

We study plasma flows above pulsar polar caps using time-dependent simulations of plasma particles in the self-consistent electric field. The flow behavior is controlled by the dimensionless parameter {alpha} = j/c{rho}{sub GJ}, where j is the electric current density and {rho}{sub GJ} is the Goldreich-Julian charge density. The region of the polar cap where 0 < {alpha} < 1 is a {sup d}ead zone{sup -}in this zone, particle acceleration is inefficient and pair creation is not expected even for young, rapidly rotating pulsars. Pulsars with polar caps near the rotation axis are predicted to have a hollow-cone structure of radiomore » emission, as the dead zone occupies the central part of the polar cap. Our results apply to charge-separated flows of electrons (j < 0) or ions (j > 0). In the latter case, we consider the possibility of a mixed flow consisting of different ion species, and observe the development of two-stream instability. The dead zone at the polar cap is essential for the development of an outer gap near the null surface {rho}{sub GJ} = 0.« less

Purification of two high molecular weight proteases from rabbit reticulocyte lysate

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

Hough, R.; Pratt, G.; Rechsteiner, M.

1987-05-01

The authors have purified two large proteases from rabbit reticulocyte lysate. The enzymes are so similar in their chromatographic behavior that each is the only significant contaminant of the other during the final stages of purification. At pH 7.8, both hydrolyze /sup 125/I-..cap alpha..-casein and 4-methylcoumaryl-7-amide (MCA) derivatives with tyrosine, phenylalanine or arginine at the P/sub 1/ position. The larger, ATP-dependent enzyme degrades ubiquitin-lysozyme conjugates, but it does not degrade unmodified lysozyme. Hydrolysis of Suc-Leu-Leu-Val-Tyr-MCA by this enzyme is also stimulated two-fold in the presence of ATP. The protease has a molecular weight of 950,000 based on sedimentation, gel filtrationmore » and non-denaturing PAGE. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the protease is composed of a number of subunits with molecular masses between 32 and 110 kDa. Densitometric analysis showed equivalent amounts of the two larger chains, and the presence of one copy of each in the native enzyme would be consistent with an M/sub r/ of 950,000. The smaller protease has a molecular weight of 700,000 and is composed of 8 to 10 subunits ranging from 21,000 to 32,000. It cleaves ubiquitin-lysozyme conjugates only slightly, and hydrolysis of conjugates or fluorogenic peptide substrates is not stimulated by ATP. This protease appears similar, if not identical, to the multicatalytic protease complex first purified by Wilk and Orlowski.« less

Quantitative assessment of serum-specific IgE in the diagnosis of human cystic echinococcosis.

PubMed

Marinova, I; Nikolov, G; Michova, A; Kurdova, R; Petrunov, B

2011-07-01

Anti-Echinococcus serum immunoglobulin (Ig)E was assessed by the ImmunoCAP system and compared with anti-Echinococcus serum IgG assessed by enzyme-linked immunosorbent assay (ELISA) and Western blot. The ImmunoCAP system revealed very high specificity (one false positive of 110 healthy individuals), low cross-reactivity (one false positive of 58 patients with other diseases) and decreased sensitivity (73.55%). Receiver operating characteristic analysis displayed a beneficial diagnostic value with high accuracy. Comparison of the ImmunoCAP system with ELISA and Western blot showed significantly higher specificity and significantly lower cross-reactivity compared with the ELISA. Examination of sera from 155 patients with cystic echinococcosis (CE) showed varying levels of anti-Echinococcus IgE (range, 0.01-118.33 kUA/L). However, most samples had moderately elevated IgE levels. Analysis of serum-specific IgE revealed significantly higher sensitivity of the ImmunoCAP system and significantly higher antibody levels in hepatic CE compared with pulmonary CE. © 2011 Blackwell Publishing Ltd.

Visual performance for trip hazard detection when using incandescent and led miner cap lamps.

PubMed

Sammarco, John J; Gallagher, Sean; Reyes, Miguel

2010-04-01

Accident data for 2003-2007 indicate that slip, trip, and falls (STFs) are the second leading accident class (17.8%, n=2,441) of lost-time injuries in underground mining. Proper lighting plays a critical role in enabling miners to detect STF hazards in this environment. Often, the only lighting available to the miner is from a cap lamp worn on the miner's helmet. The focus of this research was to determine if the spectral content of light from light-emitting diode (LED) cap lamps enabled visual performance improvements for the detection of tripping hazards as compared to incandescent cap lamps that are traditionally used in underground mining. A secondary objective was to determine the effects of aging on visual performance. The visual performance of 30 subjects was quantified by measuring each subject's speed and accuracy in detecting objects positioned on the floor both in the near field, at 1.83 meters, and far field, at 3.66 meters. Near field objects were positioned at 0 degrees and +/-20 degrees off axis, while far field objects were positioned at 0 degrees and +/-10 degrees off axis. Three age groups were designated: group A consisted of subjects 18 to 25 years old, group B consisted of subjects 40 to 50 years old, and group C consisted of subjects 51 years and older. Results of the visual performance comparison for a commercially available LED, a prototype LED, and an incandescent cap lamp indicate that the location of objects on the floor, the type of cap lamp used, and subject age all had significant influences on the time required to identify potential trip hazards. The LED-based cap lamps enabled detection times that were an average of 0.96 seconds faster compared to the incandescent cap lamp. Use of the LED cap lamps resulted in average detection times that were about 13.6% faster than those recorded for the incandescent cap lamp. The visual performance differences between the commercially available LED and prototype LED cap lamp were not statistically significant. It can be inferred from this data that the spectral content from LED-based cap lamps could enable significant visual performance improvements for miners in the detection of trip hazards. Published by Elsevier Ltd.

Calcium phosphate coupled Newcastle disease vaccine elicits humoral and cell mediated immune responses in chickens.

PubMed

Koppad, Sanganagouda; Raj, G Dhinakar; Gopinath, V P; Kirubaharan, J John; Thangavelu, A; Thiagarajan, V

2011-12-01

Calcium phosphate (CaP) particles were coupled with inactivated Newcastle disease virus (NDV) vaccine. The surface morphology of CaP particles coupled to NDV was found to be spherical, smooth and with a tendency to agglomerate. The mean (± SE) size of CaP particles was found 557.44 ± 18.62 nm. The mean percent encapsulation efficiency of CaP particles coupled to NDV assessed based on total protein content and haemagglutination (HA) activity in eluate was found to be 10.72 ± 0.89 and 12.50 ± 2.09, respectively. The humoral and cell mediated immune responses induced by CaP coupled NDV vaccine were assessed in comparison to a commercial live vaccine (RDV 'F'). CaP coupled NDV vaccine elicited prolonged haemagglutination inhibition (HI) and enzyme linked immunosorbent assay (ELISA) titres in the serum even at fourth and fifth week post-vaccination (PV), unlike RDV 'F' inoculated chickens whose titres declined to insignificant levels by this time. CaP coupled NDV vaccine could stimulate HI antibodies in tracheal washings and tears from second and first week PV, respectively. IgA ELISA antibodies were also seen in tracheal washings of these birds from third week PV and in tears from second week PV. CaP coupled NDV vaccine elicited cell mediated immune responses (CMI) from two to four weeks PV. The stimulation indices obtained after stimulation with specific antigen was not significantly different between CaP coupled antigen and live NDV virus except on first week PV. However, CaP coupled antigen did not cause suppression of lympo proliferation as indicated by statistically similar responses to mitogen, concanavalin A between the two groups. Overall, CaP coupled NDV vaccine elicited stronger and prolonged immune responses in comparison to the commercial live vaccine. No increase in the serum calcium and phosphorous levels were seen in CaP coupled NDV vaccine inoculated chickens. Copyright © 2010 Elsevier Ltd. All rights reserved.

Generation of E. coli-derived virus-like particles of porcine circovirus type 2 and their use in an indirect IgG enzyme-linked immunosorbent assay.

PubMed

Zhang, Yan; Wang, Zhanfeng; Zhan, Yang; Gong, Qian; Yu, Wanting; Deng, Zhibang; Wang, Aibing; Yang, Yi; Wang, Naidong

2016-06-01

Porcine circovirus type 2 (PCV2) causes increased mortality and poor growth or weight loss in apparently healthy swine. Therefore, methods to detect PCV2-specific antibodies in swine serum are important for prevention, diagnosis, and control of PCV2-associated diseases (PCVAD). In this study, PCV2 virus-like particles (VLPs) were used to develop a rapid, simple and economical indirect enzyme-linked immunosorbent assay to detect (with high sensitivity) PCV2-specific antibodies in swine serum. The PCV2 capsid protein (Cap) was overexpressed in E. coli after optimizing the cap gene. Subsequently, the soluble Cap was rapidly purified in one step by automated fast protein liquid chromatography (FPLC). The purified PCV2 Cap was shown by transmission electron microscopy and gel filtration chromatography to be capable of self-assembling into VLPs in vitro. Using the purified VLPs as antigens, optimal operating conditions for the VLP ELISA were determined. The concentration of PCV2 VLPs was 1 µg/ml per well, and the dilution factors for swine serum and horseradish peroxidase (HRP)-labeled goat anti-pig antibody were 1:150 and 1:4000, respectively. Out of 241 serum samples tested with this assay, 83.4 % were found to be positive. Importantly, the VLP ELISA had a total coincidence rate of 97.4 % (74/76) compared to an Ingezim PCV2 ELISA IgG assay. In summary, this rapid, inexpensive VLP ELISA has the potential to greatly facilitate large-scale investigations of PCV2-associated serotypes.

MoCAP proteins regulated by MoArk1-mediated phosphorylation coordinate endocytosis and actin dynamics to govern development and virulence of Magnaporthe oryzae

PubMed Central

Yang, Jun; Chen, Deng; Liu, Muxing; Zhang, Haifeng; Zheng, Xiaobo; Wang, Ping; Peng, Youliang; Zhang, Zhengguang

2017-01-01

Actin organization is a conserved cellular process that regulates the growth and development of eukaryotic cells. It also governs the virulence process of pathogenic fungi, such as the rice blast fungus Magnaporthe oryzae, with mechanisms not yet fully understood. In a previous study, we found that actin-regulating kinase MoArk1 displays conserved functions important in endocytosis and actin organization, and MoArk1 is required for maintaining the growth and full virulence of M. oryzae. To understand how MoArk1 might function, we identified capping protein homologs from M. oryzae (MoCAP) that interact with MoArk1 in vivo. MoCAP is heterodimer consisting of α and β subunits MoCapA and MoCapB. Single and double deletions of MoCAP subunits resulted in abnormal mycelial growth and conidia formation. The ΔMocap mutants also exhibited reduced appressorium penetration and invasive hyphal growth within host cells. Furthermore, the ΔMocap mutants exhibited delayed endocytosis and abnormal cytoskeleton assembly. Consistent with above findings, MoCAP proteins interacted with MoAct1, co-localized with actin during mycelial development, and participated in appressorial actin ring formation. Further analysis revealed that the S85 residue of MoCapA and the S285 residue of MoCapB were subject to phosphorylation by MoArk1 that negatively regulates MoCAP functions. Finally, the addition of exogenous phosphatidylinositol 4,5-bisphosphate (PIP2) failed to modulate actin ring formation in ΔMocap mutants, in contrast to the wild-type strain, suggesting that MoCAP may also mediate phospholipid signaling in the regulation of the actin organization. These results together demonstrate that MoCAP proteins whose functions are regulated by MoArk1 and PIP2 are important for endocytosis and actin dynamics that are directly linked to growth, conidiation and pathogenicity of M. oryzae. PMID:28542408

A Systems Biology Framework for Modeling Metabolic Enzyme Inhibition of Mycobacterium Tuberculosis

DTIC Science & Technology

2009-09-15

Quadri LE: Assembly of aryl-capped siderophores by modular peptide synthetases and polyketide synthases . Mol Microbiol 2000, 37:1-12. 51. Chou CJ...opportunities for therapeutic intervention. Results: We developed a mathematical framework to simulate the effects on the growth of a pathogen when enzymes in... on the growth of M. tuberculosis in a medium whose carbon source was restricted to fatty acids, and that of the 5’-O-(N-salicylsulfamoyl) adenosine

Effects of Prosodically Modulated Sub-Phonetic Variation on Lexical Competition

ERIC Educational Resources Information Center

Salverda, Anne Pier; Dahan, Delphine; Tanenhaus, Michael K.; Crosswhite, Katherine; Masharov, Mikhail; McDonough, Joyce

2007-01-01

Eye movements were monitored as participants followed spoken instructions to manipulate one of four objects pictured on a computer screen. Target words occurred in utterance-medial (e.g., "Put the cap next to the square") or utterance-final position (e.g., "Now click on the cap"). Displays consisted of the target picture (e.g., a cap), a…

Evaluation of the VetCap® treatment method for horn fly control in cattle

USDA-ARS?s Scientific Manuscript database

A field study was conducted to evaluate the efficacy of the VetCap® treatment method, (SmartVet Pty Ltd, Brisbane, Australia) to control horn flies infesting cattle. The VetCap® delivery system consists of a pressure (liquid CO2) driven launcher and an encapsulated insecticide (CyLence®) formulation...

Child psychiatry: what are we teaching medical students?

PubMed

Dingle, Arden D

2010-01-01

The author describes child and adolescent psychiatry (CAP) undergraduate teaching in American and Canadian medical schools. A survey asking for information on CAP teaching, student interest in CAP, and opinions about the CAP importance was sent to the medical student psychiatry director at 142 accredited medical schools in the United States and Canada. The results were summarized and various factors considered relevant to CAP student interest were analyzed statistically. Approximately 81% of the schools returned surveys. Most teach required CAP didactics in the preclinical and clinical years. Almost 63% of the schools have CAP clinical rotations; most are not required. Twenty-three percent of all medical students have a clinical CAP experience during their psychiatry clerkship. The majority of schools have CAP electives, and approximately 4.8% of students participate. Child and adolescent psychiatry leadership, early exposure to CAP, and CAP clinical experiences were related to student CAP interest, but these relationships were not statistically significant. The time allotted to teaching CAP in the undergraduate medical curriculum is minimal, consistent with previous survey results. Most schools require didactic instruction averaging about 12 hours and offer elective clinical opportunities. The survey findings should help direct future planning to improve CAP medical student education.

Retention Strength of Conical Welding Caps for Fixed Implant-Supported Prostheses.

PubMed

Nardi, Diego; Degidi, Marco; Sighinolfi, Gianluca; Tebbel, Florian; Marchetti, Claudio

This study evaluated the retention strength of welding caps for Ankylos standard abutments using a pull-out test. Each sample consisted of an implant abutment and its welding cap. The tests were performed with a Zwick Roell testing machine with a 1-kN load cell. The retention strength of the welding caps increased with higher abutment diameters and higher head heights and was comparable or superior to the values reported in the literature for the temporary cements used in implant dentistry. Welding caps provide a reliable connection between an abutment and a fixed prosthesis without the use of cement.

Determination of chloramphenicol residues in commercial chicken eggs in the Federal Capital Territory, Abuja, Nigeria.

PubMed

Mbodi, Felix E; Nguku, P; Okolocha, E; Kabir, J

2014-01-01

The use of antibiotics in poultry can result in residues in eggs. The joint FAO/WHO committee recommended banning the use of chloramphenicol (CAP) in food animals due to its public health hazards of aplastic anaemia, leukaemia, allergy, antibacterial resistance and carcinogenicity. This paper determines the prevalence of CAP residues in chicken eggs and assesses the usage and awareness of its ban amongst poultry farmers in the Federal Capital Territory (FCT), Abuja, Nigeria. A cross-sectional survey of registered poultry farmers in FCT was conducted using questionnaires to determine CAP administration in poultry and awareness of its ban. Pooled egg samples were collected from each poultry farm surveyed and from randomly sampled government-owned markets in FCT. Source of eggs by state were identified by the marketer at the time of collection. Samples were analysed using an enzyme-linked immunosorbent assay (ELISA) technique for the presence of CAP, and prevalence was determined. Of 288 total pooled samples collected, 257 (89.2%) were from the markets and 31 (10.8%) were from poultry farms. A total of 20 (7%) pooled egg samples tested CAP-positive; market eggs originated from 15 (41%) states of the country. Of the market eggs, 16 (6.2%) pooled samples tested positive. Of eggs from poultry farms, four (12.9%) tested positive. Mean CAP concentrations in the positive samples ranged from 0.49 to 1.17 µg kg(-1) (parts per billion). CAP use amongst poultry farmers in FCT was 75.5%; awareness of the CAP ban was 26.3%. Though 66% of veterinarians were unaware of a CAP ban, they were more likely to be aware than other poultry farmers (odds ratio (OR) = 1.4). Farm managers who use CAP were more likely to be aware of CAP ban than the farm managers not using CAP (OR = 5.5; p = 0.04). Establishing a drug residue surveillance and control program and enforcement of CAP legislation/regulation is needful to educate and prohibit the widespread CAP use amongst Nigerian poultry farmers.

Purification and characterization of novel fibrin(ogen)olytic protease from Curcuma aromatica Salisb.: Role in hemostasis.

PubMed

Shivalingu, B R; Vivek, H K; Priya, B S; Soujanya, K N; Swamy, S Nanjunda

2016-12-01

The proteases from turmeric species have procoagulant and fibrinogenolytic activity. This provides a scientific basis for traditional use of turmeric to stop bleeding and promote wound healing processes. Our previous studies revealed that fibrinogenolytic action of crude enzyme fraction of Curcuma aromatica Salisb., was found to be more influential than those of Curcuma longa L., Curcuma caesia Roxb., Curcuma amada Roxb. and Curcuma zedoria (Christm.) Roscoe. Hence, the purpose of this study is to purify and characterize protease from C. aromatica and to explore its role in wound healing process. The protease was purified by Sephadex G-50 gel permeation chromatography. Peak with potent proteolytic activity was subjected to rechromatography and then checked for homogeneity by SDS-PAGE and native PAGE. Furthermore purity of the peak was assessed by RP-HPLC and MALDI-TOF. The biochemical properties, type of protease, kinetic studies, fibrinogenolytic, coagulant and fibrinolytic activities were carried out. The two proteolytic peaks were fractionated in gel permeation chromatography. Among these, the peak-II showed potent proteolytic activity with specific activity of 10units/mg/min and named as C. aromatica protease-II (CAP-II). This protein resolved into a single sharp band both in SDS-PAGE (reducing and non-reducing) as well as in native (acidic) PAGE. It is a monomeric protein, showing sharp peak in RP-HPLC and its relative molecular mass was found to be 12.378kDa. The caseinolytic and fibrinolytic activity of CAP-II was completely inhibited by phenylmethylsulfonylfluoride (PMSF). The CAP-II exhibited optimum temperature of 45°C and optimum pH of 7.5. The Km and Vmax of CAP-II was found to be 1.616µg and 1.62units/mg/min respectively. The CAP-II showed hydrolysis of all three subunits of fibrinogen in the order Aα>Bß>γ. The CAP-II exhibited strong procoagulant activity by reducing the human plasma clotting time. It also showed fibrinolytic activity by complete hydrolysis of α-polymer and γ-γ dimer present in fibrin. The CAP-II is a novel serine protease from C. aromatica, which has been demonstrated to stop bleeding and initiate wound healing through its procoagulant and fibrin(ogen)olytic activities. Our study demonstrates the possible role of CAP-II, as therapeutic enzyme to stop bleeding at the time of wounding. Copyright © 2016 Elsevier GmbH. All rights reserved.

Effect of dietary calcium and phosphorus levels on the total tract digestibility of innate and supplemental organic and inorganic microminerals in a corn-soybean meal based diet of grower pigs.

PubMed

Jolliff, J S; Mahan, D C

2013-06-01

The effects of Ca and P (CaP) levels and micromineral sources on mineral digestibility were evaluated in growing pigs. Treatments consisted of 2 levels of CaP and 3 trace mineral (TM) treatments arranged as a 2 × 3 factorial in a randomized complete block design with 8 replicates. The CaP levels evaluated were: 1) 0.65% Ca and 0.55% P [standard CaP (Std CaP)], and 2) 1.00% Ca and 0.85% P (High CaP). The TM treatments were: 1) Basal, without supplemental TM, 2) Basal supplemented with organic TM, and 3) Basal supplemented with inorganic TM. Both organic and inorganic TM premixes added 15 mg Cu, 150 mg Fe, 10 mg Mn, 0.3 mg Se, and 140 mg Zn/kg diet. Diets were formulated using corn soybean meal with a Ca to P ratio of 1.18 in both CaP treatments. Barrows with an initial BW of 45 kg were acclimated to stainless steel metabolism crates where diets were fed for 14 d before a 10-d collection period. Pigs within replicates were fed equivalent amounts of feed at 0800 and 1600 h each day with water provided free choice. Total feces, urine, and feed orts were collected daily. Essential macro- and microminerals were analyzed by inductively coupled plasma analysis. Increasing dietary CaP decreased the digestibility of Ca and Zn. Phosphorus digestibility did not change when the P inclusion level increased from 0.55 to 0.85% Ptotal. The High CaP level resulted in a lower urinary excretion of most minerals, particularly Cu (P < 0.05) and Mn (P < 0.05), as dietary CaP level increased but the others were not statistically significant. A summary of the ATTD for each of the experimental variables was statistically analyzed and averaged for the experiment. Although there were few statistical differences with individual minerals, they generally demonstrated a decline in digestibility when the High CaP was fed, averaging a 3% lower digestibility consistently than when the Std CaP level was fed. Organic TM averaged an approximately 5% greater digestibility than the average inorganic microminerals with the difference between minerals within each source relatively consistent. These results indicate that CaP level had the greatest effect on mineral digestibility, organic microminerals had a greater digestibility than inorganic minerals, and the innate microminerals had an average apparent digestibility of 45%.

A small molecule polyamine oxidase inhibitor blocks androgen-induced oxidative stress and delays prostate cancer progression in the transgenic adenocarcinoma of the mouse prostate model.

PubMed

Basu, Hirak S; Thompson, Todd A; Church, Dawn R; Clower, Cynthia C; Mehraein-Ghomi, Farideh; Amlong, Corey A; Martin, Christopher T; Woster, Patrick M; Lindstrom, Mary J; Wilding, George

2009-10-01

High levels of reactive oxygen species (ROS) present in human prostate epithelia are an important etiologic factor in prostate cancer (CaP) occurrence, recurrence, and progression. Androgen induces ROS production in the prostate by a yet unknown mechanism. Here, to the best of our knowledge, we report for the first time that androgen induces an overexpression of spermidine/spermine N1-acetyltransferase, the rate-limiting enzyme in the polyamine oxidation pathway. As prostatic epithelia produce a large excess of polyamines, the androgen-induced polyamine oxidation that produces H2O2 could be a major reason for the high ROS levels in the prostate epithelia. A small molecule polyamine oxidase inhibitor N,N'-butanedienyl butanediamine (MDL 72,527 or CPC-200) effectively blocks androgen-induced ROS production in human CaP cells, as well as significantly delays CaP progression and death in animals developing spontaneous CaP. These data show that polyamine oxidation is not only a major pathway for ROS production in prostate, but inhibiting this pathway also successfully delays CaP progression.

Increased oxidative/nitrosative stress and decreased antioxidant enzyme activities in prostate cancer.

PubMed

Arsova-Sarafinovska, Zorica; Eken, Ayse; Matevska, Nadica; Erdem, Onur; Sayal, Ahmet; Savaser, Ayhan; Banev, Saso; Petrovski, Daniel; Dzikova, Sonja; Georgiev, Vladimir; Sikole, Aleksandar; Ozgök, Yaşar; Suturkova, Ljubica; Dimovski, Aleksandar J; Aydin, Ahmet

2009-08-01

The study was aimed to evaluate the oxidative/nitrosative stress status in prostate cancer (CaP) and benign prostatic hyperplasia (BPH). 312 men from two different populations were included: 163 men from Macedonia (73 CaP patients, 67 BPH patients and 23 control subjects) and 149 men from Turkey (34 prostate cancer patients, 100 BPH patients and 15 control subjects). We measured erythrocyte malondialdehyde (MDA) levels, erythrocyte activities of superoxide dismutase (CuZn-SOD), glutathione peroxidase (GPX) and catalase (CAT); plasma nitrite/nitrate (NO(2)(-)/NO(3)(-)), cGMP and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. A similar pattern of alteration in the oxidative/nitrosative stress-related parameters was found in both, Macedonian and Turkish studied samples: higher MDA concentrations with lower GPX and CuZn-SOD activities in CaP patients versus controls and BPH groups. The CAT activity was decreased in the CaP patients versus controls in the Turkish studied sample. Furthermore, CaP patients had increased plasma NO(2)(-)/NO(3)(-) and cGMP levels versus controls and BPH groups in both studied samples. This study has confirmed an imbalance in the oxidative stress/antioxidant status and revealed an altered nitrosative status in prostate cancer patients.

Effect of capping agents: Structural, optical and biological properties of ZnO nanoparticles

NASA Astrophysics Data System (ADS)

Javed, Rabia; Usman, Muhammad; Tabassum, Saira; Zia, Muhammad

2016-11-01

Different biological activities of capped and uncapped ZnO nanoparticles were investigated, and the effects of potential capping agents on these biological activities were studied. ZnO nanoparticles were synthesized and capped by polyethylene glycol (PEG) and polyvinyl pyrrolidone (PVP) using a simple chemical method of co-precipitation. Characterization by X-ray diffraction (XRD), Fourier transform Infrared spectroscopy (FTIR) and UV-vis spectroscopy confirmed the crystallinity, size, functional group, and band gap of synthesized nanoparticles. Reduction in size occurred from 34 nm to 26 nm due to surfactant. Results of all biological activities indicated significantly higher values in capped as compared to uncapped nanoparticles. Antibacterial activity against Staphylococcus aureus (ATCC 6538), Bacillus subtilis (ATCC 6633), Escherichia coli (ATCC15224), and Acetobacter was obtained. This activity was more prominent against Gram-positive bacteria, and ZnO-PVP nanoparticles elucidated highest antibacterial activity (zone of inhibition 17 mm) against Gram-positive, Bacillus subtilis species. Antioxidant activities including total flavonoid content, total phenolic content, total antioxidant capacity, total reducing power and %age inhibition of DPPH, and antidiabetic activity against α-amylase enzyme found to be exhibited highest by ZnO-PEG nanoparticles.

Involvement of reactive oxygen species in endosperm cap weakening and embryo elongation growth during lettuce seed germination

PubMed Central

Zhang, Yu; Chen, Bingxian; Xu, Zhenjiang; Shi, Zhaowan; Chen, Shanli; Huang, Xi; Chen, Jianxun; Wang, Xiaofeng

2014-01-01

Endosperm cap (CAP) weakening and embryo elongation growth are prerequisites for the completion of lettuce seed germination. Although it has been proposed that the cell wall loosening underlying these processes results from an enzymatic mechanism, it is still unclear which enzymes are involved. Here it is shown that reactive oxygen species (ROS), which are non-enzymatic factors, may be involved in the two processes. In Guasihong lettuce seeds imbibed in water, O2·– and H2O2 accumulated and peroxidase activity increased in the CAP, whereas its puncture force decreased. In addition, in the radicle, the increase in embryo growth potential was accompanied by accumulation of O2·– and an increase in peroxidase activity. Imbibing seeds in 0.3% sodium dichloroisocyanurate (SDIC) reduced endosperm viability and the levels of O2·–, H2O2, and peroxidase activity in the CAP, whereas the decrease in its puncture force was inhibited. However, in the embryo, SDIC did not affect the accumulation of O2·–, peroxidase activity, and the embryo growth potential. As a result, SDIC caused atypical germination, in which the endosperm ruptured at the boundary between the CAP and lateral endosperm. ROS scavengers and ROS generation inhibitors inhibited the CAP weakening and also decreased the embryo growth potential, thus decreasing the percentage of seed germination. Exogenous ROS and ROS generation inducers increased the percentage of CAP rupture to some extent, and the addition of H2O2 to 0.3% SDIC enabled some seeds to undergo typical germination. PMID:24744430

[Adaptation of critical time intervention for use in Brazil and its implementation among users of psychosocial service centers (CAPS) in the municipality of Rio de Janeiro].

PubMed

Cavalcanti, Maria Tavares; Carvalho, Maria Cecília de Araújo; Valência, Elie; Dahl, Catarina Magalhães; Souza, Flávia Mitkiewicz de

2011-12-01

Brazilian Psychiatric Reform proposes a mental healthcare model based on the implementation of a community-based service network, in which Psychosocial Service Centers (CAPS) play a fundamental role. The report presents the results of a pilot study which aimed to adapt Critical Time Intervention to the Brazilian context, and to test its feasibility to provide it to persons with schizophrenic spectrum disorders who are enrolled in CAPS of Rio de Janeiro. The research design included three inter-related phases. Phase one consisted in carrying out qualitative and quantitative field work. This phase included mapping out the socio-demographic, clinical and service utilization data of CAPS users, as well as assessing the mental health needs of participants in the study. The second phase consisted in translation of the CTI clinical manual to include the adaptations made for use in Brazil, which were based on data collected in the first phase, as well as training individuals with moderate education as CTI intervention workers. The third phase consisted of pilot implementation of the adapted intervention among a group of individuals with schizophrenia spectrum disorders enrolled in CAPS, but with difficulties in being included in treatment.

An essential role for trimethylguanosine RNA caps in Saccharomyces cerevisiae meiosis and their requirement for splicing of SAE3 and PCH2 meiotic pre-mRNAs

PubMed Central

Qiu, Zhicheng R.; Shuman, Stewart; Schwer, Beate

2011-01-01

Tgs1 is the enzyme that converts m7G RNA caps to the 2,2,7-trimethylguanosine (TMG) caps characteristic of spliceosomal snRNAs. Fungi grow vegetatively without TMG caps, thereby raising the question of what cellular transactions, if any, are TMG cap-dependent. Here, we report that Saccharomyces cerevisiae Tgs1 methyltransferase activity is essential for meiosis. tgs1Δ cells are specifically defective in splicing PCH2 and SAE3 meiotic pre-mRNAs. The TMG requirement for SAE3 splicing is alleviated by two intron mutations: a UAUUAAC to UACUAAC change that restores a consensus branchpoint and disruption of a stem–loop encompassing the branchpoint. The TMG requirement for PCH2 splicing is alleviated by a CACUAAC to UACUAAC change restoring a consensus branchpoint and by shortening the PCH2 5′ exon. Placing the SAE3 and PCH2 introns within a HIS3 reporter confers Tgs1-dependent histidine prototrophy, signifying that the respective introns are portable determinants of TMG-dependent gene expression. Analysis of in vitro splicing in extracts of TGS1 versus tgs1Δ cells showed that SAE3 intron removal was enfeebled without TMG caps, whereas splicing of ACT1 was unaffected. Our findings illuminate a new mode of tunable splicing, a reliance on TMG caps for an essential developmental RNA transaction, and three genetically distinct meiotic splicing regulons in budding yeast. PMID:21398639

An essential role for trimethylguanosine RNA caps in Saccharomyces cerevisiae meiosis and their requirement for splicing of SAE3 and PCH2 meiotic pre-mRNAs.

PubMed

Qiu, Zhicheng R; Shuman, Stewart; Schwer, Beate

2011-07-01

Tgs1 is the enzyme that converts m(7)G RNA caps to the 2,2,7-trimethylguanosine (TMG) caps characteristic of spliceosomal snRNAs. Fungi grow vegetatively without TMG caps, thereby raising the question of what cellular transactions, if any, are TMG cap-dependent. Here, we report that Saccharomyces cerevisiae Tgs1 methyltransferase activity is essential for meiosis. tgs1Δ cells are specifically defective in splicing PCH2 and SAE3 meiotic pre-mRNAs. The TMG requirement for SAE3 splicing is alleviated by two intron mutations: a UAUUAAC to UACUAAC change that restores a consensus branchpoint and disruption of a stem-loop encompassing the branchpoint. The TMG requirement for PCH2 splicing is alleviated by a CACUAAC to UACUAAC change restoring a consensus branchpoint and by shortening the PCH2 5' exon. Placing the SAE3 and PCH2 introns within a HIS3 reporter confers Tgs1-dependent histidine prototrophy, signifying that the respective introns are portable determinants of TMG-dependent gene expression. Analysis of in vitro splicing in extracts of TGS1 versus tgs1Δ cells showed that SAE3 intron removal was enfeebled without TMG caps, whereas splicing of ACT1 was unaffected. Our findings illuminate a new mode of tunable splicing, a reliance on TMG caps for an essential developmental RNA transaction, and three genetically distinct meiotic splicing regulons in budding yeast.

Validity criteria for the diagnosis of fatty liver by M probe-based controlled attenuation parameter.

PubMed

Wong, Vincent Wai-Sun; Petta, Salvatore; Hiriart, Jean-Baptiste; Cammà, Calogero; Wong, Grace Lai-Hung; Marra, Fabio; Vergniol, Julien; Chan, Anthony Wing-Hung; Tuttolomondo, Antonino; Merrouche, Wassil; Chan, Henry Lik-Yuen; Le Bail, Brigitte; Arena, Umberto; Craxì, Antonio; de Lédinghen, Victor

2017-09-01

Controlled attenuation parameter (CAP) can be performed together with liver stiffness measurement (LSM) by transient elastography (TE) and is often used to diagnose fatty liver. We aimed to define the validity criteria of CAP. CAP was measured by the M probe prior to liver biopsy in 754 consecutive patients with different liver diseases at three centers in Europe and Hong Kong (derivation cohort, n=340; validation cohort, n=414; 101 chronic hepatitis B, 154 chronic hepatitis C, 349 non-alcoholic fatty liver disease, 37 autoimmune hepatitis, 49 cholestatic liver disease, 64 others; 277 F3-4; age 52±14; body mass index 27.2±5.3kg/m 2 ). The primary outcome was the diagnosis of fatty liver, defined as steatosis involving ≥5% of hepatocytes. The area under the receiver-operating characteristics curve (AUROC) for CAP diagnosis of fatty liver was 0.85 (95% CI 0.82-0.88). The interquartile range (IQR) of CAP had a negative correlation with CAP (r=-0.32, p<0.001), suggesting the IQR-to-median ratio of CAP would be an inappropriate validity parameter. In the derivation cohort, the IQR of CAP was associated with the accuracy of CAP (AUROC 0.86, 0.89 and 0.76 in patients with IQR of CAP <20 [15% of patients], 20-39 [51%], and ≥40dB/m [33%], respectively). Likewise, the AUROC of CAP in the validation cohort was 0.90 and 0.77 in patients with IQR of CAP <40 and ≥40dB/m, respectively (p=0.004). The accuracy of CAP in detecting grade 2 and 3 steatosis was lower among patients with body mass index ≥30kg/m 2 and F3-4 fibrosis. The validity of CAP for the diagnosis of fatty liver is lower if the IQR of CAP is ≥40dB/m. Lay summary: Controlled attenuation parameter (CAP) is measured by transient elastography (TE) for the detection of fatty liver. In this large study, using liver biopsy as a reference, we show that the variability of CAP measurements based on its interquartile range can reflect the accuracy of fatty liver diagnosis. In contrast, other clinical factors such as adiposity and liver enzyme levels do not affect the performance of CAP. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Q fever community-acquired pneumonia in a patient with Crohn's disease on immunosuppressive therapy.

PubMed

Nausheen, Sara; Cunha, Burke A

2007-01-01

Community-acquired pneumonia (CAP) may be caused by typical or atypical pathogens. The three most common zoonotic atypical pathogens are Chlamydophila psittaci (psittacosis), Francisella tularensis (tularemia), and Coxiella burnetii (Q fever). Atypical CAPs are suggested by a distinctive pattern of extrapulmonary organ involvement. Zoonotic CAP may be differentiated from nonzoonotic CAP (Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionnaire's disease) by a recent zoonotic vector contact history. Zoonotic atypical CAP occurs sporadically, but not randomly, and require close association with the appropriate zoonotic vector to transmit the infection. CAP accompanied by the extrapulmonary finding of splenomegaly in a normal host limits differential diagnostic possibilities to Q fever and psittacosis. Splenomegaly does not occur with other typical or atypical CAP. Another common extrapulmonary finding occurs with some atypical pneumonias, that is, Q fever, psittacosis, and Legionnaire's disease is early mild/transient elevations of serum transaminases indicative of (hepatic) extrapulmonary organ involvement. The case presented is a middle-aged man with longstanding Crohn's disease who was further immunosuppressed by chronic prednisone therapy. The patient presented with CAP and extrapulmonary findings, that is, splenomegaly and increased serum transaminases. He denied recent contact with birds or animals. Because Crohn's disease and Q fever CAP may be accompanied by splenomegaly, the cause of his splenomegaly was a diagnostic dilemma. The patient was treated with levofloxacin. Serologic tests for atypical pathogens (Q fever, psittacosis, Legionnaire's disease, C. pneumoniae, and M. pneumoniae) were ordered. Enzyme-linked immunosorbent assay serology for Q fever was positive with elevated acute immunoglobulin-M (phase II) titers. Re-questioning of the patient revealed a recent exposure to a neighbor's parturient cat, providing the necessary zoonotic vector contact history for Q fever. The patient responded to levofloxacin, which resulted in resolution of the patient's symptoms, right lower lobe pneumonia, and splenomegaly. Because a prior abdominal computed tomography scan indicated no splenomegaly and his splenomegaly resolved with antimicrobial therapy, the splenomegaly was related to Q fever CAP.

IMF B(y) and day-night conductivity effects in the expanding polar cap convection model

NASA Technical Reports Server (NTRS)

Moses, J. J.; Gorney, D. J.; Siscoe, G. L.; Crooker, N. U.

1987-01-01

During southward B(z) periods the open field line region in the ionosphere (polar cap) expands due to increased dayside merging. Ionospheric plasma flow patterns result which can be classified by the sign of the interplanetary magnetic field (IMF) B(y) component. In this paper, a time-dependent ionospheric convection model is constructed to simulate these flows. The model consists of a spiral boundary with a gap in it. The sign of the IMF B(y) component determines the geometry of the gap. A potential is applied across the gap and distributed around the boundary. A flow results which enters the polar cap through the gap and uniformly pushes the boundary outward. Results of the model show that B(y) effects are greatest near the gap and virtually unnoticeable on the nightside of the polar cap. Adding a day-night ionospheric conductivity gradient concentrates the polar cap electric field toward dawn. The resulting flow curvature gives a sunward component that is independent of B(y). These patterns are shown to be consistent with published observations.

Active-site protein dynamics and solvent accessibility in native Achromobacter cycloclastes copper nitrite reductase.

PubMed

Sen, Kakali; Horrell, Sam; Kekilli, Demet; Yong, Chin W; Keal, Thomas W; Atakisi, Hakan; Moreau, David W; Thorne, Robert E; Hough, Michael A; Strange, Richard W

2017-07-01

Microbial nitrite reductases are denitrifying enzymes that are a major component of the global nitrogen cycle. Multiple structures measured from one crystal (MSOX data) of copper nitrite reductase at 240 K, together with molecular-dynamics simulations, have revealed protein dynamics at the type 2 copper site that are significant for its catalytic properties and for the entry and exit of solvent or ligands to and from the active site. Molecular-dynamics simulations were performed using different protonation states of the key catalytic residues (Asp CAT and His CAT ) involved in the nitrite-reduction mechanism of this enzyme. Taken together, the crystal structures and simulations show that the Asp CAT protonation state strongly influences the active-site solvent accessibility, while the dynamics of the active-site 'capping residue' (Ile CAT ), a determinant of ligand binding, are influenced both by temperature and by the protonation state of Asp CAT . A previously unobserved conformation of Ile CAT is seen in the elevated temperature series compared with 100 K structures. DFT calculations also show that the loss of a bound water ligand at the active site during the MSOX series is consistent with reduction of the type 2 Cu atom.

Salt Appetite: Interaction of Forebrain Angiotensinergic and Hindbrain Serotonergic Mechanisms

NASA Technical Reports Server (NTRS)

Menani, Jose Vanderlei; Colombari, Debora S. A.; Beltz, Terry G.; Thunhorst, Robert L.; Johnson, Alan Kim

1998-01-01

Methysergide injected into the lateral parabrachial nucleus (LPBN) increases the salt appetite of rats depleted of sodium by furosemide (FURO). The present study investigated the effects of angiotensin 2 (ANG 2) receptor blockade in the subfornical organ (SFO) on this increased salt appetite. The intake of 0.3 M NaCl and water was induced by combined administration of the diuretic, FURO, and the angiotensin-convertina, enzyme inhibitor, captopril (CAP). Pretreatment of the SFO with the anciotensin Type 1 (AT,) receptor antagonist, losartan (1 microgram/200 nl), reduced water intake but not 0.3 M NaCl intake induced by subcutaneous FURO+ CAP. Methysergide (4 microgram/200 nl) injected bilaterally into the LPBN increased 0.3 M NaCl intake after FURO + CAP. Losartan injected into the SFO prevented additional 0.3 M NaCl intake caused by methysergide injections into the LPBN. These results indicate that AT, receptors located in the SFO may have a role in mediatina the intake of sodium and water induced by sodium depletion. They also suggest that after treatment with FURO + CAP an LPBN-associated scrotonergic mechanism inhibits increased sodium intake.

A Small Molecule Polyamine Oxidase Inhibitor Blocks Androgen-Induced Oxidative Stress and Delays Prostate Cancer Progression in the TRAMP Mouse Model

PubMed Central

Basu, Hirak S.; Thompson, Todd A.; Church, Dawn R.; Clower, Cynthia C.; Mehraein-Ghomi, Farideh; Amlong, Corey A.; Martin, Christopher T.; Woster, Patrick M.; Lindstrom, Mary J.; Wilding, George

2009-01-01

High levels of reactive oxygen species (ROS) present in human prostate epithelia are an important etiological factor in prostate cancer (CaP) occurrence, recurrence and progression. Androgen induces ROS production in the prostate by a yet unknown mechanism. Here, to the best of our knowledge, we report for the first time that androgen induces an overexpression of spermidine/spermine N1-acetyltransferase (SSAT), the rate-limiting enzyme in the polyamine oxidation pathway. As prostatic epithelia produce a large excess of polyamines, the androgen-induced polyamine oxidation that produces H2O2 could be a major reason for the high ROS levels in the prostate epithelia. A small molecule polyamine oxidase inhibitor N,N'-butanedienyl butanediamine (MDL 72,527 or CPC-200) effectively blocks androgen-induced ROS production in human CaP cells as well as significantly delays CaP progression and death in animals developing spontaneous CaP. These data demonstrate that polyamine oxidation is not only a major pathway for ROS production in prostate, but inhibiting this pathway also successfully delays prostate cancer progression. PMID:19773450

Enhanced porcine circovirus Cap protein production by Pichia pastoris with a fuzzy logic DO control based methanol/sorbitol co-feeding induction strategy.

PubMed

Ding, Jian; Zhang, Chunling; Gao, Minjie; Hou, Guoli; Liang, Kexue; Li, Chunhua; Ni, Jianping; Li, Zhen; Shi, Zhongping

2014-05-10

Porcine circovirus Cap protein production by P. pastoris with strong AOX promoter suffered with the problems with traditional pure methanol induction: (1) inefficient methanol metabolism; (2) extensive oxygen supply load; (3) difficulty in stable DO control; (4) low protein titer. In this study, based on the difference of DO change patterns in response to methanol and sorbitol additions, a novel fuzzy control system was proposed to automatically regulate the co-feeding rates of methanol and sorbitol for efficient Cap protein induction. With aid of the proposed control system when setting DO control level at 10%, overall fermentation performance was significantly improved: (1) DO could be stably controlled under mild aeration condition; (2) methanol consumption rate could be restricted at moderate level and the major enzymes involved with methanol metabolism were largely activated; (3) Cap protein concentration reached a highest level of 198mg/L, which was about 64% increase over the best one using the pure methanol induction strategies. Copyright © 2014 Elsevier B.V. All rights reserved.

The role of cyclase activating (CAP) and cyclase inhibiting (CIP) parathormone fractions in the assessment of bone metabolism disturbances in women with hyperprolactinemia of various origin.

PubMed

Zadrozna-Sliwka, Beata; Bolanowski, Marek; Jawiarczyk, Aleksandra; Kaluzny, Marcin; Syrycka, Joanna

2008-02-01

Hyperprolactinemia could be one of possible causes of bone loss. The reason is thought to be connected with hypogonadism due to PRL excess and the role of other hormones like PTH and PTH-rP. There is no data on the influence of PTH fractions (CAP and CIP) on bone turnover and density in hyperprolactinemia. The aim of the study was to assess the influence of PTH and its fractions on bone metabolism in hyperprolactinemia of various origin. The study was carried out in 75 women. Group I consisted of 32 women with prolactinoma, group II consisted of 43 women with functional hyperprolactinemia. Both groups were subdivided in patients with hypogonadism and normal gonadal function. The control group consisted of 29 healthy women. In all subjects PRL, PTH and its fractions (CAP, CIP), and bone turnover markers (BAP, ICTP) were studied. BMD measurement was carried out using DXA. In patients with functional hyperprolactinemia i-PTH and CAP levels were lower than in controls. CIP concentrations were lower in patients than in controls. CAP/CIP ratio was higher in patients with prolactinoma than in patients with functional hyperprolactinemia and controls. Higher values of bone turnover markers (BAP, ICTP) in patients groups and subgroups were shown as compared to controls. Some correlations between PTH and its fractions, and BMD and bone turnover were observed. There is no direct benefit from the assessment of parathormone fractions and CAP/CIP ratio in the prognosis of bone metabolism changes in hyperprolactinemia of various origin.

Dual-Enzyme Characteristics of Polyvinylpyrrolidone-Capped Iridium Nanoparticles and Their Cellular Protective Effect against H2O2-Induced Oxidative Damage.

PubMed

Su, Hua; Liu, Dan-Dan; Zhao, Meng; Hu, Wei-Liang; Xue, Shan-Shan; Cao, Qian; Le, Xue-Yi; Ji, Liang-Nian; Mao, Zong-Wan

2015-04-22

Polyvinylpyrrolidone-stabilized iridium nanoparticles (PVP-IrNPs), synthesized by the facile alcoholic reduction method using abundantly available PVP as protecting agents, were first reported as enzyme mimics showing intrinsic catalase- and peroxidase-like activities. The preparation procedure was much easier and more importantly, kinetic studies found that the catalytic activity of PVP-IrNPs was comparable to previously reported platinum nanoparticles. Transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) characterization indicated that PVP-IrNPs had the average size of approximately 1.5 nm and mainly consisted of Ir(0) chemical state. The mechanism of PVP-IrNPs' dual-enzyme activities was investigated using XPS, Electron spin resonance (ESR) and cytochrome C-based electron transfer methods. The catalase-like activity was related to the formation of oxidized species Ir(0)@IrO2 upon reaction with H2O2. The peroxidase-like activity originated from their ability acting as electron transfer mediators during the catalysis cycle, without the production of hydroxyl radicals. Interestingly, the protective effect of PVP-IrNPs against H2O2-induced cellular oxidative damage was investigated in an A549 lung cancer cell model and PVP-IrNPs displayed excellent biocompatibility and antioxidant activity. Upon pretreatment of cells with PVP-IrNPs, the intracellular reactive oxygen species (ROS) level in response to H2O2 was decreased and the cell viability increased. This work will facilitate studies on the mechanism and biomedical application of nanomaterials-based enzyme mimic.

Inducing gravitropic curvature of primary roots of Zea mays cv Ageotropic

NASA Technical Reports Server (NTRS)

Moore, R.; Evans, M. L.; Fondren, W. M.

1990-01-01

Primary roots of the mutant 'Ageotropic' cultivar of Zea mays are nonresponsive to gravity. Their root caps secrete little or no mucilage and touch the root only at the extreme apex. A gap separates the cap and root at the periphery of the cap. Applying mucilage from normal roots or substances with a consistency similar to that of mucilage to tips of mutant roots causes these roots to become strongly graviresponsive. Gravicurvature stops when these substances are removed. Caps of some mutants secrete small amounts of mucilage and are graviresponsive. These results indicate that (a) the lack of graviresponsiveness in the mutant results from disrupting the transport pathway between the cap and root, (b) movement of the growth-modifying signal from the cap to the root occurs via an apoplastic pathway, and (c) mucilage is necessary for normal communication between the root cap and root in Zea mays cv Ageotropic.

Quinolone-based HDAC inhibitors.

PubMed

Balasubramanian, Gopalan; Kilambi, Narasimhan; Rathinasamy, Suresh; Rajendran, Praveen; Narayanan, Shridhar; Rajagopal, Sridharan

2014-08-01

HDAC inhibitors emerged as promising drug candidates in combating wide variety of cancers. At present, two of the compounds SAHA and Romidepsin were approved by FDA for cutaneous T-cell lymphoma and many are in various clinical phases. A new quinolone cap structure was explored with hydroxamic acid as zinc-binding group (ZBG). The pan HDAC inhibitory and antiproliferative activities against three human cancer cell lines HCT-116 (colon), NCI-H460 (lung) and U251 (glioblastoma) of the compounds (4a-4w) were evaluated. Introduction of heterocyclic amines in CAP region increased the enzyme inhibitory and antiproliferative activities and few of the compounds tested are metabolically stable in both MLM and HLM.

Capsaicin Synthesis Requires in Situ Phenylalanine and Valine Formation in in Vitro Maintained Placentas from Capsicum chinense.

PubMed

Baas-Espinola, Fray M; Castro-Concha, Lizbeth A; Vázquez-Flota, Felipe A; Miranda-Ham, María L

2016-06-21

Capsaicinoids (CAP) are nitrogenous metabolites formed from valine (Val) and phenylalanine (Phe) in the placentas of hot Capsicum genotypes. Placentas of Habanero peppers can incorporate inorganic nitrogen into amino acids and have the ability to secure the availability of the required amino acids for CAP biosynthesis. In order to determine the participation of the placental tissue as a supplier of these amino acids, the effects of blocking the synthesis of Val and Phe by using specific enzyme inhibitors were analyzed. Isolated placentas maintained in vitro were used to rule out external sources' participation. Blocking Phe synthesis, through the inhibition of arogenate dehydratase, significantly decreased CAP accumulation suggesting that at least part of Phe required in this process has to be produced in situ. Chlorsulfuron inhibition of acetolactate synthase, involved in Val synthesis, decreased not only Val accumulation but also that of CAP, pointing out that the requirement for this amino acid can also be fulfilled by this tissue. The presented data demonstrates that CAP accumulation in in vitro maintained placentas can be accomplished through the in situ availability of Val and Phe and suggests that the synthesis of the fatty acid chain moiety may be a limiting factor in the biosynthesis of these alkaloids.

Specificity in transition state binding: the Pauling model revisited.

PubMed

Amyes, Tina L; Richard, John P

2013-03-26

Linus Pauling proposed that the large rate accelerations for enzymes are caused by the high specificity of the protein catalyst for binding the reaction transition state. The observation that stable analogues of the transition states for enzymatic reactions often act as tight-binding inhibitors provided early support for this simple and elegant proposal. We review experimental results that support the proposal that Pauling's model provides a satisfactory explanation for the rate accelerations for many heterolytic enzymatic reactions through high-energy reaction intermediates, such as proton transfer and decarboxylation. Specificity in transition state binding is obtained when the total intrinsic binding energy of the substrate is significantly larger than the binding energy observed at the Michaelis complex. The results of recent studies that aimed to characterize the specificity in binding of the enolate oxygen at the transition state for the 1,3-isomerization reaction catalyzed by ketosteroid isomerase are reviewed. Interactions between pig heart succinyl-coenzyme A:3-oxoacid coenzyme A transferase (SCOT) and the nonreacting portions of coenzyme A (CoA) are responsible for a rate increase of 3 × 10(12)-fold, which is close to the estimated total 5 × 10(13)-fold enzymatic rate acceleration. Studies that partition the interactions between SCOT and CoA into their contributing parts are reviewed. Interactions of the protein with the substrate phosphodianion group provide an ~12 kcal/mol stabilization of the transition state for the reactions catalyzed by triosephosphate isomerase, orotidine 5'-monophosphate decarboxylase, and α-glycerol phosphate dehydrogenase. The interactions of these enzymes with the substrate piece phosphite dianion provide a 6-8 kcal/mol stabilization of the transition state for reaction of the appropriate truncated substrate. Enzyme activation by phosphite dianion reflects the higher dianion affinity for binding to the enzyme-transition state complex compared with that of the free enzyme. Evidence is presented that supports a model in which the binding energy of the phosphite dianion piece, or the phosphodianion group of the whole substrate, is utilized to drive an enzyme conformational change from an inactive open form E(O) to an active closed form E(C), by closure of a phosphodianion gripper loop. Members of the enolase and haloalkanoic acid dehalogenase superfamilies use variable capping domains to interact with nonreacting portions of the substrate and sequester the substrate from interaction with bulk solvent. Interactions of this capping domain with the phenyl group of mandelate have been shown to activate mandelate racemase for catalysis of deprotonation of α-carbonyl carbon. We propose that an important function of these capping domains is to utilize the binding interactions with nonreacting portions of the substrate to activate the enzyme for catalysis.

Specificity in Transition State Binding: The Pauling Model Revisited

PubMed Central

Amyes, Tina L.; Richard, John P.

2013-01-01

Linus Pauling proposed that the large rate accelerations for enzymes are due to the high specificity of the protein catalyst for binding the reaction transition state. The observation that stable analogs of the transition states for enzymatic reactions often act as tight-binding binding inhibitors provided early support for this simple and elegant proposal. We review experimental results which support the proposal that Pauling’s model provides a satisfactory explanation for the rate accelerations for many heterolytic enzymatic reactions through high energy reaction intermediates, such as proton transfer and decarboxylation. Specificity in transition state binding is obtained when the total intrinsic binding energy of the substrate is significantly larger than the binding energy observed at the Michaelis complex. The results of recent studies to characterize the specificity in binding of the enolate oxygen at the transition state for the 1,3-isomerization reaction catalyzed by ketosteroid isomerase are reviewed. Interactions between pig heart succinyl-CoA:3-oxoacid coenzyme A transferase (SCOT) and the nonreacting portions of CoA are responsible for a rate increase of 3 × 1012-fold, which is close to the estimated total 5 × 1013-fold enzymatic rate acceleration. Studies that partition the interactions between SCOT and CoA into their contributing parts are reviewed. Interactions of the protein with the substrate phosphodianion group provide a ca. 12 kcal/mol stabilization of the transition state for the reactions catalyzed by triosephosphate isomerase, orotidine 5′-monophosphate decarboxylase and α-glycerol phosphate dehydrogenase. The interactions of these enzymes with the substrate piece phosphite dianion provide a 6 – 8 kcal/mol stabilization of the transition state for reaction of the appropriate truncated substrate. Enzyme activation by phosphite dianion reflects the higher dianion affinity for binding to the enzyme-transition state complex compared with the free enzyme. Evidence is presented that supports a model in which the binding energy of the phosphite dianion piece, or the phosphodianion group of the whole substrate, is utilized to drive an enzyme conformational change from an inactive open form EO to an active closed form EC, by closure of a phosphodianion gripper loop. Members of the enolase and haloalkanoic acid dehalogenase superfamilies use variable capping domains to interact with nonreacting portions of the substrate and sequester the substrate from interaction with bulk solvent. Interactions of this capping domain with the phenyl group of mandelate have been shown to activate mandelate racemase for catalysis of deprotonation of α-carbonyl carbon. We propose that an important function of these capping domains is to utilize the binding interactions with nonreacting portions of the substrate to activate the enzyme for catalysis. PMID:23327224

[The experimental research of inner ear metabolism and electrical physiology of autoimmune sensorineural hearing loss].

PubMed

Tan, C; Cao, Y; Hu, P

1998-09-01

Inquire into the mechanism of inner ear pathological physiology in autoimmune sensorineural hearing loss (ASHL). With the auditory electric-physiological techniques and enzyme-histochemical method, the change of inner ear hearing function and enzyme activity were observed. These animals, which threshold of auditory nerve compound active potential (CAP) and cochlear microphonic potential(CM) heightening evidently, showed that the amplitude of endolymphatic potential(EP) (include-EP) bring down in various degrees, which was related to the change of the active of Na(+)-K(+)-ATPase and SDH in vascularis stria and endolymphatic sac. The abnormality of enzymes metabolism in inner ear tissues, which following autoimmune inflammation damage, is the pathological foundation of hearing dysfunction.

Severe community-acquired Enterobacter pneumonia: a plea for greater awareness of the concept of health-care-associated pneumonia

PubMed Central

2011-01-01

Background Patients with Enterobacter community-acquired pneumonia (EnCAP) were admitted to our intensive care unit (ICU). Our primary aim was to describe them as few data are available on EnCAP. A comparison with CAP due to common and typical bacteria was performed. Methods Baseline clinical, biological and radiographic characteristics, criteria for health-care-associated pneumonia (HCAP) were compared between each case of EnCAP and thirty age-matched typical CAP cases. A univariate and multivariate logistic regression analysis was performed to determine factors independently associated with ENCAP. Their outcome was also compared. Results In comparison with CAP due to common bacteria, a lower leukocytosis and constant HCAP criteria were associated with EnCAP. Empiric antibiotic therapy was less effective in EnCAP (20%) than in typical CAP (97%) (p < 0.01). A delay in the initiation of appropriate antibiotic therapy (3.3 ± 1.6 vs. 1.2 ± 0.6 days; p < 0.01) and an increase in duration of mechanical ventilation (8.4 ± 5.2 vs. 4.0 ± 4.3 days; p = 0.01) and ICU stay were observed in EnCAP patients. Conclusions EnCAP is a severe infection which is more consistent with HCAP than with typical CAP. This retrospectively suggests that the application of HCAP guidelines should have improved EnCAP management. PMID:21569334

North Polar Cap

NASA Technical Reports Server (NTRS)

2004-01-01

7 September 2004 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a 1.4 m/pixel (5 ft/pixel) view of a typical martian north polar ice cap texture. The surface is pitted and rough at the scale of several meters. The north polar residual cap of Mars consists mainly of water ice, while the south polar residual cap is mostly carbon dioxide. This picture is located near 85.2oN, 283.2oW. The image covers an area approximately 1 km wide by 1.4 km high (0.62 by 0.87 miles). Sunlight illuminates this scene from the lower left.

Box H/ACA snoRNAs are preferred substrates for the trimethylguanosine synthase in the divergent unicellular eukaryote Trichomonas vaginalis

PubMed Central

Simoes-Barbosa, Augusto; Chakrabarti, Kausik; Pearson, Michael; Benarroch, Delphine; Shuman, Stewart; Johnson, Patricia J.

2012-01-01

The 2,2,7-trimethylguanosine caps of eukaryal snRNAs and snoRNA are formed by the enzyme Tgs1, which catalyzes sequential guanine-N2 methylations of m7G caps. Atypically, in the divergent unicellular eukaryote Trichomonas vaginalis, spliceosomal snRNAs lack a guanosine cap and the recombinant T. vaginalis trimethylguanosine synthase (TvTgs) produces only m2,7G in vitro. Here, we show by direct metabolic labeling that endogenous T. vaginalis RNAs contain m7G, m2,7G, and m2,2,7G caps. Immunodepletion of TvTgs from cell extracts and TvTgs add-back experiments demonstrate that TvTgs produces m2,7G and m2,2,7G caps. Expression of TvTgs in yeast tgs1Δ cells leads to the formation of m2,7G and m2,2,7G caps and complementation of the lethality of a tgs1Δ mud2Δ strain. Whereas TvTgs is present in the nucleus and cytosol of T. vaginalis cells, TMG-containing RNAs are localized primarily in the nucleolus. Molecular cloning of anti-TMG affinity-purified T. vaginalis RNAs identified 16 box H/ACA snoRNAs, which are implicated in guiding RNA pseudouridylation. The ensemble of new T. vaginalis H/ACA snoRNAs allowed us to predict and partially validate an extensive map of pseudouridines in T. vaginalis rRNA. PMID:22847815

Comparsion of an immunochromatographic strip with ELISA for simultaneous detection of thiamphenicol, florfenicol and chloramphenicol in food samples.

PubMed

Guo, Lingling; Song, Shanshan; Liu, Liqiang; Peng, Juan; Kuang, Hua; Xu, Chuanlai

2015-09-01

Rapid and sensitive indirect competitive enzyme-linked immunosorbent assays (ic-ELISA) and gold nanoparticle immunochromatographic strip tests were developed to detect thiamphenicol (TAP), florfenicol (FF) and chloramphenicol (CAP) in milk and honey samples. The generic monoclonal antibody for TAP, FF and CAP was prepared based on a hapten [D-threo-1-(4-aminophenyl)-2- dichloroacetylamino-1,3-propanediol], and the haptenwas linked to a carrier protein using the diazotization method. After the optimization of several parameters (coating, pH, sodium chloride content and methanol content), the ic-ELISA was established. The quantitative working range for TAP was 0.11-1.36 ng/mL, with an IC50 of 0.39 ng/mL. The optimized ELISA showed cross-reactivity to CAP (300%) and FF (15.6%), with IC50 values of 0.13 and 2.5 ng/mL, respectively. The analytical recovery of TAP, FF and CAP in milk and honey samples in the ic-ELISA ranged from 81.2 to 112.9%. Based on this monoclonal antibody, a rapid and sensitive immunochromatographic test strip was also developed. This strip had a detection limit of 1 ng/mL for TAP, FF and CAP in milk and honey samples. Moreover, the test was completed within 10 min. Our results showed that the proposed ic-ELISA and immunochromatographic test strip method are highly useful screening tools for TAP, FF and CAP detection in milk and honey samples. Copyright © 2015 John Wiley & Sons, Ltd.

Adenylyl cyclase-associated protein-1/CAP1 as a biological target substrate of gelatinase B/MMP-9

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

Cauwe, Benedicte; Martens, Erik; Van den Steen, Philippe E.

2008-09-10

Matrix metalloproteinases (MMPs) are classically associated with the turnover of secreted structural and functional proteins. Although MMPs have been shown to process also a kaleidoscope of membrane-associated substrates, little is known about the processing of intracellular proteins by MMPs. Physiological and pathological cell apoptosis, necrosis and tumor lysis by chemotherapy, radiotherapy or immunological cytotoxicity, are examples of conditions in which an overload of intracellular proteins becomes accessible to the action of MMPs. We used a model system of dying human myelomonocytic cells to study the processing of intracellular protein substrates by gelatinase B/MMP-9 in vitro. Adenylyl cyclase-associated protein-1 or CAP1more » was identified as a novel and most efficient substrate of gelatinase B/MMP-9. The presence of CAP1 in the extracellular milieu in vivo was documented by analysis of urine of patients with systemic autoimmune diseases. Whereas no active MMP-9 could be detected in urines of healthy controls, all urine samples of patients with clinical parameters of renal failure contained activated MMP-9 and/or MMP-2. In addition, in some of these patients indications of CAP1 cleavage are observed, implying CAP1 degradation in vivo. The high turnover rate of CAP1 by MMP-9, comparable to that of gelatin as the natural extracellular substrate of this enzyme, may be critical to prevent pathological conditions associated with considerable cytolysis.« less

Two Routes to Genetic Suppression of RNA Trimethylguanosine Cap Deficiency via C-Terminal Truncation of U1 snRNP Subunit Snp1 or Overexpression of RNA Polymerase Subunit Rpo26.

PubMed

Qiu, Zhicheng R; Schwer, Beate; Shuman, Stewart

2015-04-24

The trimethylguanosine (TMG) caps of small nuclear (sn) RNAs are synthesized by the enzyme Tgs1 via sequential methyl additions to the N2 atom of the m(7)G cap. Whereas TMG caps are inessential for Saccharomyces cerevisiae vegetative growth at 25° to 37°, tgs1∆ cells that lack TMG caps fail to thrive at 18°. The cold-sensitive defect correlates with ectopic stoichiometric association of nuclear cap-binding complex (CBC) with the residual m(7)G cap of the U1 snRNA and is suppressed fully by Cbc2 mutations that weaken cap binding. Here, we show that normal growth of tgs1∆ cells at 18° is also restored by a C-terminal deletion of 77 amino acids from the Snp1 subunit of yeast U1 snRNP. These results underscore the U1 snRNP as a focal point for TMG cap function in vivo. Casting a broader net, we conducted a dosage suppressor screen for genes that allowed survival of tgs1∆ cells at 18°. We thereby recovered RPO26 (encoding a shared subunit of all three nuclear RNA polymerases) and RPO31 (encoding the largest subunit of RNA polymerase III) as moderate and weak suppressors of tgs1∆ cold sensitivity, respectively. A structure-guided mutagenesis of Rpo26, using rpo26∆ complementation and tgs1∆ suppression as activity readouts, defined Rpo26-(78-155) as a minimized functional domain. Alanine scanning identified Glu89, Glu124, Arg135, and Arg136 as essential for rpo26∆ complementation. The E124A and R135A alleles retained tgs1∆ suppressor activity, thereby establishing a separation-of-function. These results illuminate the structure activity profile of an essential RNA polymerase component. Copyright © 2015 Qiu et al.

indCAPS: A tool for designing screening primers for CRISPR/Cas9 mutagenesis events.

PubMed

Hodgens, Charles; Nimchuk, Zachary L; Kieber, Joseph J

2017-01-01

Genetic manipulation of organisms using CRISPR/Cas9 technology generally produces small insertions/deletions (indels) that can be difficult to detect. Here, we describe a technique to easily and rapidly identify such indels. Sequence-identified mutations that alter a restriction enzyme recognition site can be readily distinguished from wild-type alleles using a cleaved amplified polymorphic sequence (CAPS) technique. If a restriction site is created or altered by the mutation such that only one allele contains the restriction site, a polymerase chain reaction (PCR) followed by a restriction digest can be used to distinguish the two alleles. However, in the case of most CRISPR-induced alleles, no such restriction sites are present in the target sequences. In this case, a derived CAPS (dCAPS) approach can be used in which mismatches are purposefully introduced in the oligonucleotide primers to create a restriction site in one, but not both, of the amplified templates. Web-based tools exist to aid dCAPS primer design, but when supplied sequences that include indels, the current tools often fail to suggest appropriate primers. Here, we report the development of a Python-based, species-agnostic web tool, called indCAPS, suitable for the design of PCR primers used in dCAPS assays that is compatible with indels. This tool should have wide utility for screening editing events following CRISPR/Cas9 mutagenesis as well as for identifying specific editing events in a pool of CRISPR-mediated mutagenesis events. This tool was field-tested in a CRISPR mutagenesis experiment targeting a cytokinin receptor (AHK3) in Arabidopsis thaliana. The tool suggested primers that successfully distinguished between wild-type and edited alleles of a target locus and facilitated the isolation of two novel ahk3 null alleles. Users can access indCAPS and design PCR primers to employ dCAPS to identify CRISPR/Cas9 alleles at http://indcaps.kieber.cloudapps.unc.edu/.

The Est3 protein associates with yeast telomerase through an OB-fold domain

PubMed Central

Lee, Jaesung S.; Mandell, Edward K.; Tucey, Timothy M.; Morris, Danna K.; Victoria, Lundblad

2009-01-01

The Est3 protein is a small regulatory subunit of yeast telomerase which is dispensable for enzyme catalysis but essential for telomere replication in vivo. Using structure prediction combined with in vivo characterization, we show here that Est3 consists of a predicted OB (oligo-saccharide/oligo-nucleotide binding) fold. Mutagenesis of predicted surface residues was used to generate a functional map of one surface of Est3, which identified a site that mediates association with the telomerase complex. Surprisingly, the predicted OB-fold of Est3 is structurally similar to the OB-fold of the mammalian TPP1 protein, despite the fact that Est3 and TPP1, as components of telomerase and a telomere capping complex, respectively, perform functionally distinct tasks at chromosome ends. The analysis performed on Est3 may be instructive in generating comparable missense mutations on the surface of the OB-fold domain of TPP1. PMID:19172754

Capped RNA primer binding to influenza polymerase and implications for the mechanism of cap-binding inhibitors

PubMed Central

Pflug, Alexander; Gaudon, Stephanie; Resa-Infante, Patricia; Lethier, Mathilde; Reich, Stefan; Schulze, Wiebke M

2018-01-01

Abstract Influenza polymerase uses short capped primers snatched from nascent Pol II transcripts to initiate transcription of viral mRNAs. Here we describe crystal structures of influenza A and B polymerase bound to a capped primer in a configuration consistent with transcription initiation (’priming state’) and show by functional assays that conserved residues from both the PB2 midlink and cap-binding domains are important for positioning the capped RNA. In particular, mutation of PB2 Arg264, which interacts with the triphosphate linkage in the cap, significantly and specifically decreases cap-dependent transcription. We also compare the configuration of the midlink and cap-binding domains in the priming state with their very different relative arrangement (called the ‘apo’ state) in structures where the potent cap-binding inhibitor VX-787, or a close analogue, is bound. In the ‘apo’ state the inhibitor makes additional interactions to the midlink domain that increases its affinity beyond that to the cap-binding domain alone. The comparison suggests that the mechanism of resistance of certain mutations that allow virus to escape from VX-787, notably PB2 N510T, can only be rationalized if VX-787 has a dual mode of action, direct inhibition of capped RNA binding as well as stabilization of the transcriptionally inactive ‘apo’ state. PMID:29202182

Telomete length in peripheral blood mononuclear cells is associated with folate status in men

USDA-ARS?s Scientific Manuscript database

Human chromosomes are capped by tandem repeats of DNA and associated proteins termed telomeres. The length of the telomeres is reduced with increasing cell divisions except when the enzyme telomerase is active as seen in stem cells and germ cells. Telomere dysfunction has been associated with deve...

Magnetic vortices in nanocaps induced by curvature

NASA Astrophysics Data System (ADS)

Abdelgawad, Ahmed M.; Nambiar, Nikhil; Bapna, Mukund; Chen, Hao; Majetich, Sara A.

2018-05-01

Magnetic nanoparticles with room temperature remanent magnetic vortices stabilized by their curvature are very intriguing due to their potential use in biomedicine. In the present study, we investigate room temperature magnetic chirality in 100 nm diameter permalloy spherical caps with 10 nm and 30 nm thicknesses. Micromagnetic OOMMF simulations predict the equilibrium spin structure for these caps to form a vortex state. We fabricate the permalloy caps by sputtering permalloy on both close-packed and sparse arrays of polystyrene nanoparticles. Magnetic force microscopy scans show a clear signature of a vortex state in close-packed caps of both 10 nm and 30 nm thicknesses. Alternating gradient magnetometry measurements of the caps are consistent with a remnant vortex state in 30 nm thick caps and a transition to an onion state followed by a vortex state in 10 nm thick caps. Out-of-plane measurements supported by micromagnetic simulations shows that an out-of-plane field can stabilize a vortex state down to a diameter of 15 nm.

Effect of capping layer on spin-orbit torques

NASA Astrophysics Data System (ADS)

Sun, Chi; Siu, Zhuo Bin; Tan, Seng Ghee; Yang, Hyunsoo; Jalil, Mansoor B. A.

2018-04-01

In order to enhance the magnitude of spin-orbit torque (SOT), considerable experimental works have been devoted to studying the thickness dependence of the different layers in multilayers consisting of heavy metal (HM), ferromagnet (FM), and capping layers. Here, we present a theoretical model based on the spin-drift-diffusion formalism to investigate the effect of the capping layer properties such as its thickness on the SOT observed in experiments. It is found that the spin Hall-induced SOT can be significantly enhanced by incorporating a capping layer with an opposite spin Hall angle to that of the HM layer. The spin Hall torque can be maximized by tuning the capping layer thickness. However, in the absence of the spin Hall effect (SHE) in the capping layer, the torque decreases monotonically with the capping layer thickness. Conversely, the spin Hall torque is found to decrease monotonically with the FM layer thickness, irrespective of the presence or absence of the SHE in the capping layer. All these trends are in correspondence with experimental observations. Finally, our model suggests that capping layers with a long spin diffusion length and high resistivity would also enhance the spin Hall torque.

Absolute configuration of a chiral CHD group via neutron diffraction: confirmation of the absolute stereochemistry of the enzymatic formation of malic acid

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

Bau, R.; Brewer, I.; Chiang, M.Y.

Neutron diffraction has been used to monitor the absolute stereochemistry of an enzymatic reaction. (-)(2S)malic-3-d acid was prepared by the action of fumarase on fumaric acid in D/sub 2/O. After a large number of cations were screened, it was found that (+)(R)..cap alpha..-phenylethylamine forms the large crystals necessary for a neutron diffraction analysis. The subsequent structure determination showed that (+)(R)..cap alpha..-phenylethylammonium (-)(2S)malate-3-d has an absolute configuration of R at the CHD site. This result confirms the absolute stereochemistry of fumarate-to-malate transformation as catalyzed by the enzyme fumarase.

Spectroscopic investigations on the effect of N-Acetyl-L-cysteine-Capped CdTe Quantum Dots on catalase

NASA Astrophysics Data System (ADS)

Sun, Haoyu; Yang, Bingjun; Cui, Erqian; Liu, Rutao

2014-11-01

Quantum dots (QDs) are recognized as some of the most promising semiconductor nanocrystals in biomedical applications. However, the potential toxicity of QDs has aroused wide public concern. Catalase (CAT) is a common enzyme in animal and plant tissues. For the potential application of QDs in vivo, it is important to investigate the interaction of QDs with CAT. In this work, the effect of N-Acetyl-L-cysteine-Capped CdTe Quantum Dots with fluorescence emission peak at 612 nm (QDs-612) on CAT was investigated by fluorescence, synchronous fluorescence, fluorescence lifetime, ultraviolet-visible (UV-vis) absorption and circular dichroism (CD) techniques. Binding of QDs-612 to CAT caused static quenching of the fluorescence, the change of the secondary structure of CAT and the alteration of the microenvironment of tryptophan residues. The association constants K were determined to be K288K = 7.98 × 105 L mol-1 and K298K = 7.21 × 105 L mol-1. The interaction between QDs-612 and CAT was spontaneous with 1:1 stoichiometry approximately. The CAT activity was also inhibited for the bound QDs-612. This work provides direct evidence about enzyme toxicity of QDs-612 to CAT in vitro and establishes a new strategy to investigate the interaction between enzyme and QDs at a molecular level, which is helpful for clarifying the bioactivities of QDs in vivo.

The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5): Development and initial psychometric evaluation in military veterans.

PubMed

Weathers, Frank W; Bovin, Michelle J; Lee, Daniel J; Sloan, Denise M; Schnurr, Paula P; Kaloupek, Danny G; Keane, Terence M; Marx, Brian P

2018-03-01

The Clinician-Administered PTSD Scale (CAPS) is an extensively validated and widely used structured diagnostic interview for posttraumatic stress disorder (PTSD). The CAPS was recently revised to correspond with PTSD criteria in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5; American Psychiatric Association, 2013). This article describes the development of the CAPS for DSM-5 (CAPS-5) and presents the results of an initial psychometric evaluation of CAPS-5 scores in 2 samples of military veterans (Ns = 165 and 207). CAPS-5 diagnosis demonstrated strong interrater reliability (к = .78 to 1.00, depending on the scoring rule) and test-retest reliability (к = .83), as well as strong correspondence with a diagnosis based on the CAPS for DSM-IV (CAPS-IV; к = .84 when optimally calibrated). CAPS-5 total severity score demonstrated high internal consistency (α = .88) and interrater reliability (ICC = .91) and good test-retest reliability (ICC = .78). It also demonstrated good convergent validity with total severity score on the CAPS-IV (r = .83) and PTSD Checklist for DSM-5 (r = .66) and good discriminant validity with measures of anxiety, depression, somatization, functional impairment, psychopathy, and alcohol abuse (rs = .02 to .54). Overall, these results indicate that the CAPS-5 is a psychometrically sound measure of DSM-5 PTSD diagnosis and symptom severity. Importantly, the CAPS-5 strongly corresponds with the CAPS-IV, which suggests that backward compatibility with the CAPS-IV was maintained and that the CAPS-5 provides continuity in evidence-based assessment of PTSD in the transition from DSM-IV to DSM-5 criteria. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Electron polar cap and the boundary of open geomagnetic field lines.

NASA Technical Reports Server (NTRS)

Evans, L. C.; Stone, E. C.

1972-01-01

A total of 333 observations of the boundary of the polar access region for electrons (energies greater than 530 keV) provides a comprehensive map of the electron polar cap. The boundary of the electron polar cap, which should occur at the latitude separating open and closed field lines, is consistent with previously reported closed field line limits determined from trapped-particle data. The boundary, which is sharply defined, seems to occur at one of three discrete latitudes. Although the electron flux is generally uniform across the polar cap, a limited region of reduced access is observed about 10% of the time.

Lateral parabrachial nucleus and serotonergic mechanisms in the control of salt appetite in rats.

PubMed

Menani, J V; Thunhorst, R L; Johnson, A K

1996-01-01

This study investigated the effects of bilateral injections of serotonergic receptor agonist and antagonist into the lateral parabrachial nucleus (LPBN) on the ingestion of water and 0.3 M NaCl induced by intracerebroventricular angiotensin II (ANG II) or by combined subcutaneous injections of the diuretic furosemide (Furo) and the angiotensin-converting enzyme inhibitor captopril (Cap). Rats had stainless steel cannulas implanted bilaterally into the LPBN and into the left lateral ventricle. Bilateral LPBN pretreatment with the serotonergic 5-HT1/5-HT2 receptor antagonist methysergide (4 micrograms/200 nl each site) increased 0.3 M NaCl and water intakes induced by intracerebroventricular ANG II (50 ng/microliter) and 0.3 M NaCl intake induced by subcutaneous Furo + Cap. Pretreatment with bilateral LPBN injections of a serotonergic 5-HT2A/2C receptor agonist DOI (5 micrograms/200 nl) significantly reduced 0.3 M NaCl intake induced by subcutaneous Furo + Cap. Pretreatment with methysergide or DOI into the LPBN produced no significant changes in the water intake induced by subcutaneous Furo + Cap. These results suggest that serotonergic mechanisms associated with the LPBN may have inhibitory roles in water and sodium ingestion in rats.

Etiological analysis and predictive diagnostic model building of community-acquired pneumonia in adult outpatients in Beijing, China.

PubMed

Liu, Ya-Fen; Gao, Yan; Chen, Mei-Fang; Cao, Bin; Yang, Xiao-Hua; Wei, Lai

2013-07-09

Etiological epidemiology and diagnosis are important issues in adult community-acquired pneumonia (CAP), and identifying pathogens based on patient clinical features is especially a challenge. CAP-associated main pathogens in adults include viruses as well as bacteria. However, large-scale epidemiological investigations of adult viral CAP in China are still lacking. In this study, we analyzed the etiology of adult CAP in Beijing, China and constructed diagnostic models based on combinations of patient clinical factors. A multicenter cohort was established with 500 adult CAP outpatients enrolled in Beijing between November 2010 to October 2011. Multiplex and quantitative real-time fluorescence PCR were used to detect 15 respiratory viruses and mycoplasma pneumoniae, respectively. Bacteria were detected with culture and enzyme immunoassay of the Streptococcus pneumoniae urinary antigen. Univariate analysis, multivariate analysis, discriminatory analysis and Receiver Operating Characteristic (ROC) curves were used to build predictive models for etiological diagnosis of adult CAP. Pathogens were detected in 54.2% (271/500) of study patients. Viruses accounted for 36.4% (182/500), mycoplasma pneumoniae for 18.0% (90/500) and bacteria for 14.4% (72/500) of the cases. In 182 of the patients with viruses, 219 virus strains were detected, including 166 single and 53 mixed viral infections. Influenza A virus represented the greatest proportion with 42.0% (92/219) and 9.1% (20/219) in single and mixed viral infections, respectively. Factors selected for the predictive etiological diagnostic model of viral CAP included cough, dyspnea, absence of chest pain and white blood cell count (4.0-10.0) × 10(9)/L, and those of mycoplasma pneumoniae CAP were being younger than 45 years old and the absence of a coexisting disease. However, these models showed low accuracy levels for etiological diagnosis (areas under ROC curve for virus and mycoplasma pneumoniae were both 0.61, P < 0.05). Greater consideration should be given to viral and mycoplasma pneumoniae infections in adult CAP outpatients. While predictive etiological diagnostic models of viral and mycoplasma pneumoniae based on combinations of demographic and clinical factors may provide indications of etiology, diagnostic confirmation of CAP remains dependent on laboratory pathogen test results.

Direct competitive chemiluminescence immunoassays based on gold-coated magnetic particles for detection of chloramphenicol.

PubMed

Liang, Xiaohui; Fang, Xiangyi; Yao, Manwen; Yang, Yucong; Li, Junfeng; Liu, Hongjun; Wang, Linyu

2016-02-01

Direct competitive chemiluminescence immunoassays (CLIA) based on gold-coated magnetic nanospheres (Au-MNPs) were developed for rapid analysis of chloramphenicol (CAP). The Au-MNPs were modified with carboxyl groups and amino groups by 11-mercaptoundecanoic acid (MUA) and cysteamine respectively, and then were respectively conjugated with CAP base and CAP succinate via an activating reaction using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). NSP-DMAE-NHS, a new and effective luminescence reagent, was employed to label anti-CAP antibody (mAb) as a tracer in direct CLIA for CAP detection using a 'homemade' luminescent measurement system that was set up with a photomultiplier tube (PMT) and a photon counting unit linked to a computer. The sensitivities and limits of detection (LODs) of the two methods were obtained and compared according to the inhibition curves. The 50% inhibition concentration (IC50 ) values of the two methods were about 0.044 ng/mL and 0.072 ng/mL respectively and LODs were approximately 0.001 ng/mL and 0.006 ng/mL respectively. To our knowledge, they were much more sensitive than any traditional enzyme-linked immunosorbent assay (ELISA) ever reported. Moreover, the new luminescence reagent NSP-DMAE-NHS is much more sensitive and stable than luminol and its derivatives, contributing to the sensitivity enhancement. Copyright © 2015 John Wiley & Sons, Ltd.

Androgen receptor requires JunD as a coactivator to switch on an oxidative stress generation pathway in prostate cancer cells.

PubMed

Mehraein-Ghomi, Farideh; Basu, Hirak S; Church, Dawn R; Hoffmann, F Michael; Wilding, George

2010-06-01

Relatively high oxidative stress levels in the prostate are postulated to be a major factor for prostate carcinogenesis and prostate cancer (CaP) progression. We focused on elucidating metabolic pathways of oxidative stress generation in CaP cells. Previously, we showed that the transcription factor JunD is essential for androgen-induced reactive oxygen species (ROS) production in androgen-dependent human CaP cells. We also recently showed that androgen induces the first and regulatory enzyme spermidine/spermine N1-acetyltransferase (SSAT) in a polyamine catabolic pathway that produces copious amounts of metabolic ROS. Here, we present coimmunoprecipitation and Gaussia luciferase reconstitution assay data that show that JunD forms a complex with androgen-activated androgen receptor (AR) in situ. Our chromatin immunoprecipitation assay data show that JunD binds directly to a specific SSAT promoter sequence only in androgen-treated LNCaP cells. Using a vector containing a luciferase reporter gene connected to the SSAT promoter and a JunD-silenced LNCaP cell line, we show that JunD is essential for androgen-induced SSAT gene expression. The elucidation of JunD-AR complex inducing SSAT expression leading to polyamine oxidation establishes the mechanistic basis of androgen-induced ROS production in CaP cells and opens up a new prostate-specific target for CaP chemopreventive/chemotherapeutic drug development. Copyright 2010 AACR.

EXACERBATION OF ATHEROSCLEROSIS FOLLOWING EXPOSURE TO VARIOUS COMBUSTION SOURCE PARTICLES

EPA Science Inventory

Exposure of ApoE knockout (ApoE^-/-) mice to concentrated ambient particles (CAPs) has been shown to increase arterial plaque area and size. CAPs are a complex aerosol mixture consisting of wind-blown dust, emissions from the combustion of fossil fuels, and secondary tr...

New AdoMet Analogues as Tools for Enzymatic Transfer of Photo-Cross-Linkers and Capturing RNA-Protein Interactions.

PubMed

Muttach, Fabian; Mäsing, Florian; Studer, Armido; Rentmeister, Andrea

2017-05-02

Elucidation of biomolecular interactions is of utmost importance in biochemistry. Photo-cross-linking offers the possibility to precisely determine RNA-protein interactions. However, despite the inherent specificity of enzymes, approaches for site-specific introduction of photo-cross-linking moieties into nucleic acids are scarce. Methyltransferases in combination with synthetic analogues of their natural cosubstrate S-adenosyl-l-methionine (AdoMet) allow for the post-synthetic site-specific modification of biomolecules. We report on three novel AdoMet analogues bearing the most widespread photo-cross-linking moieties (aryl azide, diazirine, and benzophenone). We show that these photo-cross-linkers can be enzymatically transferred to the methyltransferase target, that is, the mRNA cap, with high efficiency. Photo-cross-linking of the resulting modified mRNAs with the cap interacting protein eIF4E was successful with aryl azide and diazirine but not benzophenone, reflecting the affinity of the modified 5' caps. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mutations in STAMBP, encoding a deubiquitinating enzyme, cause Microcephaly-Capillary Malformation syndrome

PubMed Central

McDonell, Laura M.; Mirzaa, Ghayda M.; Alcantara, Diana; Schwartzentruber, Jeremy; Carter, Melissa T.; Lee, Leo J.; Clericuzio, Carol L.; Graham, John M.; Morris-Rosendahl, Deborah J.; Polster, Tilman; Acsadi, Gyula; Townshend, Sharron; Williams, Simon; Halbert, Anne; Isidor, Bertrand; Smyser, Christopher D.; Paciorkowski, Alex R.; Willing, Marcia; Woulfe, John; Das, Soma; Beaulieu, Chandree L.; Marcadier, Janet; Geraghty, Michael T.; Frey, Brendan J.; Majewski, Jacek; Bulman, Dennis E.; Dobyns, William B.; O’Driscoll, Mark; Boycott, Kym M.

2014-01-01

Microcephaly-capillary malformation (MIC-CAP) syndrome exhibits severe microcephaly with progressive cortical atrophy, intractable epilepsy, profound developmental delay and multiple small capillary malformations on the skin. We employed whole-exome sequencing of five patients with MIC-CAP syndrome and identified novel recessive mutations in STAMBP, a gene encoding the deubiquitinating (DUB) isopeptidase STAMBP (STAM-binding protein)/AMSH (Associated Molecule with the SH3 domain of STAM), that plays a key role in cell surface receptor-mediated endocytosis and sorting. Patient cell lines showed reduced STAMBP expression associated with accumulation of ubiquitin-conjugated protein aggregates, elevated apoptosis and insensitive activation of the RAS-MAPK and PI3K-AKT-mTOR pathways. The latter cellular phenotype is significant considering the established connection between these pathways and their association with vascular and capillary malformations. Furthermore, our findings of a congenital human disorder caused by a defective DUB protein that functions in endocytosis, implicates ubiquitin-conjugate aggregation and elevated apoptosis as factors potentially influencing the progressive neuronal loss underlying MIC-CAP. PMID:23542699

Clinical Characteristics of Q Fever and Etiology of Community-Acquired Pneumonia in a Tropical Region of Southern Taiwan: A Prospective Observational Study

PubMed Central

Lai, Chung-Hsu; Chang, Lin-Li; Lin, Jiun-Nong; Chen, Wei-Fang; Wei, Yu-Feng; Chiu, Chien-Tung; Wu, Jiun-Ting; Hsu, Chi-Kuei; Chen, Jung-Yueh; Lee, Ho-Sheng; Lin, Hsi-Hsun; Chen, Yen-Hsu

2014-01-01

Background The clinical characteristics of Q fever are poorly identified in the tropics. Fever with pneumonia or hepatitis are the dominant presentations of acute Q fever, which exhibits geographic variability. In southern Taiwan, which is located in a tropical region, the role of Q fever in community-acquired pneumonia (CAP) has never been investigated. Methodology/Principal Findings During the study period, May 2012 to April 2013, 166 cases of adult CAP and 15 cases of acute Q fever were prospectively investigated. Cultures of clinical specimens, urine antigen tests for Streptococcus pneumoniae and Legionella pneumophila, and paired serologic assessments for Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Q fever (Coxiella burnetii) were used for identifying pathogens associated with CAP. From April 2004 to April 2013 (the pre-study period), 122 cases of acute Q fever were also included retrospectively for analysis. The geographic distribution of Q fever and CAP cases was similar. Q fever cases were identified in warmer seasons and younger ages than CAP. Based on multivariate analysis, male gender, chills, thrombocytopenia, and elevated liver enzymes were independent characteristics associated with Q fever. In patients with Q fever, 95% and 13.5% of cases presented with hepatitis and pneumonia, respectively. Twelve (7.2%) cases of CAP were seropositive for C. burnetii antibodies, but none of them had acute Q fever. Among CAP cases, 22.9% had a CURB-65 score ≧2, and 45.8% had identifiable pathogens. Haemophilus parainfluenzae (14.5%), S. pneumoniae (6.6%), Pseudomonas aeruginosa (4.8%), and Klebsiella pneumoniae (3.0%) were the most common pathogens identified by cultures or urine antigen tests. Moreover, M. pneumoniae, C. pneumoniae, and co-infection with 2 pathogens accounted for 9.0%, 7.8%, and 1.8%, respectively. Conclusions In southern Taiwan, Q fever is an endemic disease with hepatitis as the major presentation and is not a common etiology of CAP. PMID:25033402

Crystal Structures of Two Bacterial 3-Hydroxy-3-methylglutaryl-CoA Lyases Suggest a Common Catalytic Mechanism among a Family of TIM Barrel Metalloenzymes Cleaving Carbon-Carbon Bonds

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

Forouhar,F.; Hussain, M.; Farid, R.

The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) lyase catalyzes the terminal steps in ketone body generation and leucine degradation. Mutations in this enzyme cause a human autosomal recessive disorder called primary metabolic aciduria, which typically kills victims because of an inability to tolerate hypoglycemia. Here we present crystal structures of the HMG-CoA lyases from Bacillus subtilis and Brucella melitensis at 2.7 and 2.3 {angstrom} resolution, respectively. These enzymes share greater than 45% sequence identity with the human orthologue. Although the enzyme has the anticipated triose-phosphate isomerase (TIM) barrel fold, the catalytic center contains a divalent cation-binding site formed by a cluster ofmore » invariant residues that cap the core of the barrel, contrary to the predictions of homology models. Surprisingly, the residues forming this cation-binding site and most of their interaction partners are shared with three other TIM barrel enzymes that catalyze diverse carbon-carbon bond cleavage reactions believed to proceed through enolate intermediates (4-hydroxy-2-ketovalerate aldolase, 2-isopropylmalate synthase, and transcarboxylase 5S). We propose the name 'DRE-TIM metallolyases' for this newly identified enzyme family likely to employ a common catalytic reaction mechanism involving an invariant Asp-Arg-Glu (DRE) triplet. The Asp ligates the divalent cation, while the Arg probably stabilizes charge accumulation in the enolate intermediate, and the Glu maintains the precise structural alignment of the Asp and Arg. We propose a detailed model for the catalytic reaction mechanism of HMG-CoA lyase based on the examination of previously reported product complexes of other DRE-TIM metallolyases and induced fit substrate docking studies conducted using the crystal structure of human HMG-CoA lyase (reported in the accompanying paper by Fu, et al. (2006) J. Biol. Chem. 281, 7526-7532). Our model is consistent with extensive mutagenesis results and can guide subsequent studies directed at definitive experimental elucidation of this enzyme's reaction mechanism.« less

The X-ray Crystallographic Structure and Activity Analysis of a Pseudomonas-Specific Subfamily of the HAD Enzyme Superfamily Evidences a Novel Biochemical Function

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

Peisach,E.; Wang, L.; Burroughs, A.

2008-01-01

The haloacid dehalogenase (HAD) superfamily is a large family of proteins dominated by phosphotransferases. Thirty-three sequence families within the HAD superfamily (HADSF) have been identified to assist in function assignment. One such family includes the enzyme phosphoacetaldehyde hydrolase (phosphonatase). Phosphonatase possesses the conserved Rossmanniod core domain and a C1-type cap domain. Other members of this family do not possess a cap domain and because the cap domain of phosphonatase plays an important role in active site desolvation and catalysis, the function of the capless family members must be unique. A representative of the capless subfamily, PSPTO{_}2114, from the plant pathogenmore » Pseudomonas syringae, was targeted for catalytic activity and structure analyses. The X-ray structure of PSPTO{_}2114 reveals a capless homodimer that conserves some but not all of the intersubunit contacts contributed by the core domains of the phosphonatase homodimer. The region of the PSPTO{_}2114 that corresponds to the catalytic scaffold of phosphonatase (and other HAD phosphotransfereases) positions amino acid residues that are ill suited for Mg+2 cofactor binding and mediation of phosphoryl group transfer between donor and acceptor substrates. The absence of phosphotransferase activity in PSPTO{_}2114 was confirmed by kinetic assays. To explore PSPTO{_}2114 function, the conservation of sequence motifs extending outside of the HADSF catalytic scaffold was examined. The stringently conserved residues among PSPTO{_}2114 homologs were mapped onto the PSPTO{_}2114 three-dimensional structure to identify a surface region unique to the family members that do not possess a cap domain. The hypothesis that this region is used in protein-protein recognition is explored to define, for the first time, HADSF proteins which have acquired a function other than that of a catalyst. Proteins 2008.« less

Biocatalytic induction of supramolecular order

NASA Astrophysics Data System (ADS)

Hirst, Andrew R.; Roy, Sangita; Arora, Meenakshi; Das, Apurba K.; Hodson, Nigel; Murray, Paul; Marshall, Stephen; Javid, Nadeem; Sefcik, Jan; Boekhoven, Job; van Esch, Jan H.; Santabarbara, Stefano; Hunt, Neil T.; Ulijn, Rein V.

2010-12-01

Supramolecular gels, which demonstrate tunable functionalities, have attracted much interest in a range of areas, including healthcare, environmental protection and energy-related technologies. Preparing these materials in a reliable manner is challenging, with an increased level of kinetic defects observed at higher self-assembly rates. Here, by combining biocatalysis and molecular self-assembly, we have shown the ability to more quickly access higher-ordered structures. By simply increasing enzyme concentration, supramolecular order expressed at molecular, nano- and micro-levels is dramatically enhanced, and, importantly, the gelator concentrations remain identical. Amphiphile molecules were prepared by attaching an aromatic moiety to a dipeptide backbone capped with a methyl ester. Their self-assembly was induced by an enzyme that hydrolysed the ester. Different enzyme concentrations altered the catalytic activity and size of the enzyme clusters, affecting their mobility. This allowed structurally diverse materials that represent local minima in the free energy landscape to be accessed based on a single gelator structure.

Purification and properties of poliovirus RNA polymerase expressed in Escherichia coli

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

Plotch, S.J.; Palant, O.; Gluzman, Y.

1989-01-01

A cDNA clone encoding the RNA polymerase of poliovirus has been expressed in Escherichia coli under the transcriptional control of a T7 bacteriophage promoter. This poliovirus enzyme was designed to contain only a single additional amino acid, the N-terminal methionine. The recombinant enzyme has been purified to near homogeneity, and polyclonal antibodies have been prepared against it. The enzyme exhibits poly(A)-dependent oligo(U)-primed ply(U) polymerase activity as well as RNA polymerase activity. In the presence of an oligo(U) primer, the enzyme catalyzes the synthesis of a full-length copy of either poliovirus or globin RNA templates. In the absence of added primer,more » RNA products up to twice the length of the template are synthesized. When incubated in the presence of a single nucleoside triphosphate, (..cap alpha..-/sup 32/P)UTP, the enzyme catalyzes the incorporation of radioactive label into template RNA. These results are discussed in light of previously proposed models of poliovirus RNA synthesis in vitro.« less

Charge-switchable gold nanoparticles for enhanced enzymatic thermostability.

PubMed

Shankar, Shiv; Soni, Sarvesh K; Daima, Hemant K; Selvakannan, P R; Khire, Jayant M; Bhargava, Suresh K; Bansal, Vipul

2015-09-07

This study illustrates a facile strategy for efficient immobilization of enzymes on a metal nanoparticle surface. The strategy proposed here enables the enzymatic activity to be retained while increasing the enzyme thermostability. It is demonstrated that the use of a zwitterionic amino acid tyrosine as a reducing and capping agent to synthesise gold nanoparticles allows efficient immobilization of phytase enzyme through charge-switchable electrostatic interactions. The detailed kinetic and thermodynamic studies reveal that the proposed enzyme immobilization strategy improves the overall quality of phytase by reducing the activation energy required for substrate hydrolysis and broadening the temperature window in which immobilized enzyme is able to operate. The outcomes of this study indicate that the underlying zwitterionic nature of 20 natural amino acids along with significant variability in their isoelectric points and hydropathy indices as well the ability of some of the amino acids to reduce metal ions is likely to offer significant opportunities for tailoring nano-bio interfaces in a rational manner for a range of biological applications.

Psychometric Properties and Factor Structure of the German Version of the Clinician-Administered PTSD Scale for DSM-5.

PubMed

Müller-Engelmann, Meike; Schnyder, Ulrich; Dittmann, Clara; Priebe, Kathlen; Bohus, Martin; Thome, Janine; Fydrich, Thomas; Pfaltz, Monique C; Steil, Regina

2018-05-01

The Clinician-Administered PTSD Scale (CAPS) is a widely used diagnostic interview for posttraumatic stress disorder (PTSD). Following fundamental modifications in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ( DSM-5), the CAPS had to be revised. This study examined the psychometric properties (internal consistency, interrater reliability, convergent and discriminant validity, and structural validity) of the German version of the CAPS-5 in a trauma-exposed sample ( n = 223 with PTSD; n =51 without PTSD). The results demonstrated high internal consistency (αs = .65-.93) and high interrater reliability (ICCs = .81-.89). With regard to convergent and discriminant validity, we found high correlations between the CAPS severity score and both the Posttraumatic Diagnostic Scale sum score ( r = .87) and the Beck Depression Inventory total score ( r = .72). Regarding the underlying factor structure, the hybrid model demonstrated the best fit, followed by the anhedonia model. However, we encountered some nonpositive estimates for the correlations of the latent variables (factors) for both models. The model with the best fit without methodological problems was the externalizing behaviors model, but the results also supported the DSM-5 model. Overall, the results demonstrate that the German version of the CAPS-5 is a psychometrically sound measure.

Structural analysis and immunoregulation activity comparison of five polysaccharides from Angelica sinensis.

PubMed

Wang, Junmin; Ge, Beilei; Li, Zihong; Guan, Fangxia; Li, Feifei

2016-04-20

Four fractional polysaccharides (CAPS30, CAPS50, CAPS70 and CAPS80) and total polysaccharides (CAPSt) were obtained from Angelica sinensis. Their structures were identified by Fourier transform-infrared spectroscopy (FT-IR), molecular weights were evaluated by high performance gel permeation chromatography (HPGPC) and compositions were analyzed by gas chromatography-mass spectrometry (GC-MS). Their immunoregulation activities were further compared in vitro. The results showed that they displayed different structural features and immuno-enhancement activities. They all could cause the proliferation of the lymphocyte, up-regulate stimulate the productions of IFN-γ, IL-2, IL-6 and TNF-α secretion in the peripheral lymphocytes. Further experiments showed that CAPS50 and CAPS70 could increase the ratio of CD3(+)CD56(+) cells to some extent. These indicated that five CAPSs displayed different activities which were associated with their different structural characteristics and CAPS70, with the molecular weights of 20.82kDa and consisting of mannose and glucose in the molar ratio of 1.20:1.01, possessed the strongest immuno-enhancement activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Munc13 homology domain-1 in CAPS/UNC31 mediates SNARE binding required for priming vesicle exocytosis.

PubMed

Khodthong, Chuenchanok; Kabachinski, Greg; James, Declan J; Martin, Thomas F J

2011-08-03

Neuropeptide and peptide hormone secretion from neural and endocrine cells occurs by Ca(2+)-triggered dense-core vesicle exocytosis. The membrane fusion machinery consisting of vesicle and plasma membrane SNARE proteins needs to be assembled for Ca(2+)-triggered vesicle exocytosis. The related Munc13 and CAPS/UNC31 proteins that prime vesicle exocytosis are proposed to promote SNARE complex assembly. CAPS binds SNARE proteins and stimulates SNARE complex formation on liposomes, but the relevance of SNARE binding to CAPS function in cells had not been determined. Here we identify a core SNARE-binding domain in CAPS as corresponding to Munc13 homology domain-1 (MHD1). CAPS lacking a single helix in MHD1 was unable to bind SNARE proteins or to support the Ca(2+)-triggered exocytosis of either docked or newly arrived dense-core vesicles. The results show that MHD1 is a SNARE-binding domain and that SNARE protein binding is essential for CAPS function in dense-core vesicle exocytosis. Copyright © 2011 Elsevier Inc. All rights reserved.

3D spherical-cap fitting procedure for (truncated) sessile nano- and micro-droplets & -bubbles.

PubMed

Tan, Huanshu; Peng, Shuhua; Sun, Chao; Zhang, Xuehua; Lohse, Detlef

2016-11-01

In the study of nanobubbles, nanodroplets or nanolenses immobilised on a substrate, a cross-section of a spherical cap is widely applied to extract geometrical information from atomic force microscopy (AFM) topographic images. In this paper, we have developed a comprehensive 3D spherical-cap fitting procedure (3D-SCFP) to extract morphologic characteristics of complete or truncated spherical caps from AFM images. Our procedure integrates several advanced digital image analysis techniques to construct a 3D spherical-cap model, from which the geometrical parameters of the nanostructures are extracted automatically by a simple algorithm. The procedure takes into account all valid data points in the construction of the 3D spherical-cap model to achieve high fidelity in morphology analysis. We compare our 3D fitting procedure with the commonly used 2D cross-sectional profile fitting method to determine the contact angle of a complete spherical cap and a truncated spherical cap. The results from 3D-SCFP are consistent and accurate, while 2D fitting is unavoidably arbitrary in the selection of the cross-section and has a much lower number of data points on which the fitting can be based, which in addition is biased to the top of the spherical cap. We expect that the developed 3D spherical-cap fitting procedure will find many applications in imaging analysis.

Comparative dose-response assessment of various combustion source particles to indcue acute lung-injury and exacerbate atherosclerosis in ApoE-Mice

EPA Science Inventory

Exposure to concentrated ambient particles (CAPs) has been shown to increase arterial plaque area and size in atherosclerosis susceptible mice. CAPs are a complex aerosol mixture consisting of wind-blown dust. emissions from the combustion of fossil fuels, and secondary transform...

A Fair Slice of the Cake? Distributing the 'Capped' Further Education Pool.

ERIC Educational Resources Information Center

Cane, Brian; Seavor, Ken

1980-01-01

In Great Britain the Advanced Further Education Pool supports polytechnics and colleges. Although the "pool" of expenditure has been "capped," allocations for 1980/81 were dependent on the size of claims made by individual authorities. It is suggested that these claims bear no consistent relationship to past expenditure or…

Elevation Changes of Ice Caps in the Canadian Arctic Archipelago

NASA Technical Reports Server (NTRS)

Abdalati, W.; Krabill, W.; Frederick, E.; Manizade, S.; Martin, C.; Sonntag, J.; Swift, R.; Thomas, R.; Yungel, J.; Koerner, R.

2004-01-01

Precise repeat airborne laser surveys were conducted over the major ice caps in the Canadian Arctic Archipelago in the spring of 1995 and 2000 in order to measure elevation changes in the region. Our measurements reveal thinning at lower elevations (below 1600 m) on most of the ice caps and glaciers, but either very little change or thickening at higher elevations in the ice cap accumulation zones. Recent increases in precipitation in the area can account for the slight thickening where it was observed, but not for the thinning at lower elevations. For the northern ice caps on the Queen Elizabeth Islands, thinning was generally less than 0.5 m/yr , which is consistent with what would be expected from the warm temperature anomalies in the region for the 5-year period between surveys and appears to be a continuation of a trend that began in the mid 1980s. Further south, however, on the Barnes and Penny ice caps on Baffin Island, this thinning was much more pronounced at over 1 m/yr in the lower elevations. Here temperature anomalies were very small, and the thinning at low elevations far exceeds any associated enhanced ablation. The observations on Barnes, and perhaps Penny are consistent with the idea that the observed thinning is part of a much longer term deglaciation, as has been previously suggested for Barnes Ice Cap. Based on the regional relationships between elevation and elevation-change in our data, the 1995-2000 mass balance for the region is estimated to be 25 cu km/yr of ice, which corresponds to a sea level increase of 0.064 mm/ yr . This places it among the more significant sources of eustatic sea level rise, though not as substantial as Greenland ice sheet, Alaskan glaciers, or the Patagonian ice fields.

COLLAPSED ABNORMAL POLLEN1 Gene Encoding the Arabinokinase-Like Protein Is Involved in Pollen Development in Rice1[C][W][OA

PubMed Central

Ueda, Kenji; Yoshimura, Fumiaki; Miyao, Akio; Hirochika, Hirohiko; Nonomura, Ken-Ichi; Wabiko, Hiroetsu

2013-01-01

We isolated a pollen-defective mutant, collapsed abnormal pollen1 (cap1), from Tos17 insertional mutant lines of rice (Oryza sativa). The cap1 heterozygous plant produced equal numbers of normal and collapsed abnormal grains. The abnormal pollen grains lacked almost all cytoplasmic materials, nuclei, and intine cell walls and did not germinate. Genetic analysis of crosses revealed that the cap1 mutation did not affect female reproduction or vegetative growth. CAP1 encodes a protein consisting of 996 amino acids that showed high similarity to Arabidopsis (Arabidopsis thaliana) l-arabinokinase, which catalyzes the conversion of l-arabinose to l-arabinose 1-phosphate. A wild-type genomic DNA segment containing CAP1 restored mutants to normal pollen grains. During rice pollen development, CAP1 was preferentially expressed in anthers at the bicellular pollen stage, and the effects of the cap1 mutation were mainly detected at this stage. Based on the metabolic pathway of l-arabinose, cap1 pollen phenotype may have been caused by toxic accumulation of l-arabinose or by inhibition of cell wall metabolism due to the lack of UDP-l-arabinose derived from l-arabinose 1-phosphate. The expression pattern of CAP1 was very similar to that of another Arabidopsis homolog that showed 71% amino acid identity with CAP1. Our results suggested that CAP1 and related genes are critical for pollen development in both monocotyledonous and dicotyledonous plants. PMID:23629836

Fibroblast activation protein is induced by inflammation and degrades type I collagen in thin-cap fibroatheromata

PubMed Central

Brokopp, Chad E.; Schoenauer, Roman; Richards, Peter; Bauer, Stefan; Lohmann, Christine; Emmert, Maximilian Y.; Weber, Benedikt; Winnik, Stephan; Aikawa, Elena; Graves, Kirk; Genoni, Michele; Vogt, Peter; Lüscher, Thomas F.; Renner, Christoph; Hoerstrup, Simon P.; Matter, Christian M.

2011-01-01

Aims Collagen degradation in atherosclerotic plaques with thin fibrous caps renders them more prone to rupture. Fibroblast activation protein (FAP) plays a role in arthritis and tumour formation through its collagenase activity. However, the significance of FAP in thin-cap human fibroatheromata remains unknown. Methods and results We detected enhanced FAP expression in type IV–V human aortic atheromata (n = 12), compared with type II–III lesions (n = 9; P < 0.01) and healthy aortae (n = 8; P < 0.01) by immunostaining and western blot analyses. Fibroblast activation protein was also increased in thin-cap (<65 µm) vs. thick-cap (≥65 µm) human coronary fibroatheromata (n = 12; P < 0.01). Fibroblast activation protein was expressed by human aortic smooth muscle cells (HASMC) as shown by colocalization on immunofluorescent aortic plaque stainings (n = 10; P < 0.01) and by flow cytometry in cell culture. Although macrophages did not express FAP, macrophage burden in human aortic plaques correlated with FAP expression (n = 12; R2= 0.763; P < 0.05). Enzyme-linked immunosorbent assays showed a time- and dose-dependent up-regulation of FAP in response to human tumour necrosis factor α (TNFα) in HASMC (n = 6; P < 0.01). Moreover, supernatants from peripheral blood-derived macrophages induced FAP expression in cultured HASMC (n = 6; P < 0.01), an effect abolished by blocking TNFα (n = 6; P < 0.01). Fibroblast activation protein associated with collagen-poor regions in human coronary fibrous caps and digested type I collagen and gelatin in vitro (n = 6; P < 0.01). Zymography revealed that FAP-mediated collagenase activity was neutralized by an antibody directed against the FAP catalytic domain both in HASMC (n = 6; P < 0.01) and in fibrous caps of atherosclerotic plaques (n = 10; P < 0.01). Conclusion Fibroblast activation protein expression in HASMC is induced by macrophage-derived TNFα. Fibroblast activation protein associates with thin-cap human coronary fibroatheromata and contributes to type I collagen breakdown in fibrous caps. PMID:21292680

South Polar Cap, Summer 2000

NASA Technical Reports Server (NTRS)

2000-01-01

This is the south polar cap of Mars as it appeared to the Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) on April 17, 2000. In winter and early spring, this entire scene would be covered by frost. In summer, the cap shrinks to its minimum size, as shown here. Even though it is summer, observations made by the Viking orbiters in the 1970s showed that the south polar cap remains cold enough that the polar frost (seen here as white) consists of carbon dioxide. Carbon dioxide freezes at temperatures around -125o C (-193o F). Mid-summer afternoon sunlight illuminates this scene from the upper left from about 11.2o above the horizon. Soon the cap will experience sunsets; by June 2000, this pole will be in autumn, and the area covered by frost will begin to grow. Winter will return to the south polar region in December 2000. The polar cap from left to right is about 420 km (260 mi) across.

Observations of the north polar region of Mars from the Mars orbiter laser altimeter.

PubMed

Zuber, M T; Smith, D E; Solomon, S C; Abshire, J B; Afzal, R S; Aharonson, O; Fishbaugh, K; Ford, P G; Frey, H V; Garvin, J B; Head, J W; Ivanov, A B; Johnson, C L; Muhleman, D O; Neumann, G A; Pettengill, G H; Phillips, R J; Sun, X; Zwally, H J; Banerdt, W B; Duxbury, T C

1998-12-11

Elevations from the Mars Orbiter Laser Altimeter (MOLA) have been used to construct a precise topographic map of the martian north polar region. The northern ice cap has a maximum elevation of 3 kilometers above its surroundings but lies within a 5-kilometer-deep hemispheric depression that is contiguous with the area into which most outflow channels emptied. Polar cap topography displays evidence of modification by ablation, flow, and wind and is consistent with a primarily H2O composition. Correlation of topography with images suggests that the cap was more spatially extensive in the past. The cap volume of 1.2 x 10(6) to 1.7 x 10(6) cubic kilometers is about half that of the Greenland ice cap. Clouds observed over the polar cap are likely composed of CO2 that condensed out of the atmosphere during northern hemisphere winter. Many clouds exhibit dynamical structure likely caused by the interaction of propagating wave fronts with surface topography.

Construction of plasmid, bacterial expression, purification, and assay of dengue virus type 2 NS5 methyltransferase.

PubMed

Boonyasuppayakorn, Siwaporn; Padmanabhan, Radhakrishnan

2014-01-01

Dengue virus (DENV), a member of mosquito-borne flavivirus, causes self-limiting dengue fever as well as life-threatening dengue hemorrhagic fever and dengue shock syndrome. Its positive sense RNA genome has a cap at the 5'-end and no poly(A) tail at the 3'-end. The viral RNA encodes a single polyprotein, C-prM-E-NS1-NS2A-NS2B-NS3-NS4A-NS4B-NS5. The polyprotein is processed into 3 structural proteins (C, prM, and E) and 7 nonstructural (NS) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5). NS3 and NS5 are multifunctional enzymes performing various tasks in viral life cycle. The N-terminal domain of NS5 has distinct GTP and S-adenosylmethionine (SAM) binding sites. The role of GTP binding site is implicated in guanylyltransferase (GTase) activity of NS5. The SAM binding site is involved in both N-7 and 2'-O-methyltransferase (MTase) activities involved in formation of type I cap. The C-terminal domain of NS5 catalyzes RNA-dependent RNA polymerase (RdRp) activity involved in RNA synthesis. We describe the construction of the MTase domain of NS5 in an E. coli expression vector, purification of the enzyme, and conditions for enzymatic assays of N7- and 2'O-methyltransferase activities that yield the final type I 5'-capped RNA ((7Me)GpppA2'OMe-RNA).

Myofibril growth during cardiac hypertrophy is regulated through dual phosphorylation and acetylation of the actin capping protein CapZ

PubMed Central

Lin, Ying-Hsi; Warren, Chad M.; Li, Jieli; McKinsey, Timothy A.; Russell, Brenda

2016-01-01

The mechanotransduction signaling pathways initiated in heart muscle by increased mechanical loading are known to lead to long-term transcriptional changes and hypertrophy, but the rapid events for adaptation at the sarcomeric level are not fully understood. The goal of this study was to test the hypothesis that actin filament assembly during cardiomyocyte growth is regulated by post-translational modifications (PTMs) of CapZβ1. In rapidly hypertrophying neonatal rat ventricular myocytes (NRVMs) stimulated by phenylephrine (PE), two-dimensional gel electrophoresis (2DGE) of CapZβ1 revealed a shift toward more negative charge. Consistent with this, mass spectrometry identified CapZβ1 phosphorylation on serine-204 and acetylation on lysine-199, two residues which are near the actin binding surface of CapZβ1. Ectopic expression of dominant negative PKCε (dnPKCε) in NRVMs blunted the PE-induced increase in CapZ dynamics, as evidenced by the kinetic constant (Kfrap) of fluorescence recovery after photobleaching (FRAP), and concomitantly reduced phosphorylation and acetylation of CapZβ1. Furthermore, inhibition of class I histone deacetylases (HDACs) increased lysine-199 acetylation on CapZβ1, which increased Kfrap of CapZ and stimulated actin dynamics. Finally, we show that PE treatment of NRVMs results in decreased binding of HDAC3 to myofibrils, suggesting a signal-dependent mechanism for the regulation of sarcomere-associated CapZβ1 acetylation. Taken together, this dual regulation through phosphorylation and acetylation of CapZβ1 provides a novel model for the regulation of myofibril growth during cardiac hypertrophy. PMID:27185186

Toxicological implications of selenium nanoparticles with different coatings along with Se4+ on Lemna minor.

PubMed

Tarrahi, Roshanak; Khataee, Alireza; Movafeghi, Ali; Rezanejad, Farkhondeh; Gohari, Gholamreza

2017-08-01

Nanoparticles have potential high risks for living organisms in the environment due to their specific qualities and their easy access. In the present study, selenium nanoparticles (Se NPs) with two different coatings (l-cysteine and tannic acid) were synthesized. The characteristics of particles were analyzed using XRD, FT-IR and SEM. The impact of the nanoparticles besides Se 4+ , on the aquatic higher plant Lemna minor was evaluated and compared. Entrance of l-cysteine and tannic acid capped Se NPs in the roots of Lemna minor was proved by TEM and fluorescence microscopy. Adverse effects of mentioned NPs and differences of these effects from those by sodium selenite as the ionic form were assessed by a range of biophysicochemical tests. Altogether, the results asserted that Lemna minor was notably poisoned by both capped Se NPs and Se 4+ . Thus, growth and photosynthetic pigments were decreased while lipid peroxidation along with total phenol and flavonoid contents were raised. Eventually some changes in enzymatic activities were presented. To sum up the consequences, it can be concluded that all changes occurred due to the plant defense system especially in order to remove reactive oxygen species (ROS) and possible phytotoxicity originated by l- cysteine and tannic acid capped Se NPs in addition to Se 4+ . The influence of tannic acid capped Se NPs after sodium selenite is stronger by the means of antioxidant enzymes activity in comparison with l-cysteine capped Se NPs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Enzyme activity of α-chymotrypsin: Deactivation by gold nano-cluster and reactivation by glutathione.

PubMed

Ghosh, Catherine; Mondal, Tridib; Bhattacharyya, Kankan

2017-05-15

Effect of gold nanoclusters (Au-NCs) on the circular dichroism (CD) spectra and enzymatic activity of α-chymotrypsin (ChT) (towards hydrolysis of a substrate, N-succinyl-l-phenylalanine p-nitroanilide) are studied. The CD spectra indicate that on binding to Au-NC, ChT is completely unfolded, resulting in nearly zero ellipticity. α-chymotrypsin (ChT) coated gold nano-clusters exhibit almost no enzymatic activity. Addition of glutathione (GSH) or oxidized glutathione (GSSG) restore the enzyme activity of α-chymotrypsin by 30-45%. ChT coated Au-NC exhibits two emission maxima-one at 480nm (corresponding to Au 10 ) and one at 640nm (Au 25 ). On addition of glutathione (GSH) or oxidized glutathione (GSSG) the emission peak at 640nm vanishes and only one peak at 480nm (Au 10 ) remains. MALDI mass spectrometry studies suggest addition of glutathione (GSH) to α-chymotrypsin capped Au-NCs results in the formation of glutathione-capped Au-NCs and α-chymotrypsin is released from Au-NCs. CD spectroscopy indicates that the conformation of the released α-chymotrypsin is different from that of the native α-chymotrypsin. Copyright © 2017 Elsevier Inc. All rights reserved.

Preliminary characterization of (nucleoside-2′-O-)-methyltransferase crystals from Meaban and Yokose flaviviruses

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

Mastrangelo, Eloise; Bollati, Michela; Milani, Mario

2006-08-01

Two methyltransferases from flaviviruses (Meaban and Yokose viruses) have been overexpressed and crystallized. Diffraction data and characterization of the two crystal forms are presented, together with a preliminary molecular-replacement solution for both enzymes. Viral methyltranferases (MTase) are involved in the third step of the mRNA-capping process, transferring a methyl group from S-adenosyl-l-methionine (SAM) to the capped mRNA. MTases are classified into two groups: (guanine-N7)-methyltransferases (N7MTases), which add a methyl group onto the N7 atom of guanine, and (nucleoside-2′-O-)-methyltransferases (2′OMTases), which add a methyl group to a ribose hydroxyl. The MTases of two flaviviruses, Meaban and Yokose viruses, have been overexpressed,more » purified and crystallized in complex with SAM. Characterization of the crystals together with details of preliminary X-ray diffraction data collection (at 2.8 and 2.7 Å resolution, respectively) are reported here. The sequence homology relative to Dengue virus 2′OMTase and the structural conservation of specific residues in the putative active sites suggest that both enzymes belong to the 2′OMTase subgroup.« less

A Point Mutation in the Exon Junction Complex Factor Y14 Disrupts Its Function in mRNA Cap Binding and Translation Enhancement*

PubMed Central

Chuang, Tzu-Wei; Lee, Kuo-Ming; Lou, Yuan-Chao; Lu, Chia-Chen; Tarn, Woan-Yuh

2016-01-01

Eukaryotic mRNA biogenesis involves a series of interconnected steps mediated by RNA-binding proteins. The exon junction complex core protein Y14 is required for nonsense-mediated mRNA decay (NMD) and promotes translation. Moreover, Y14 binds the cap structure of mRNAs and inhibits the activity of the decapping enzyme Dcp2. In this report, we show that an evolutionarily conserved tryptophan residue (Trp-73) of Y14 is critical for its binding to the mRNA cap structure. A Trp-73 mutant (W73V) bound weakly to mRNAs and failed to protect them from degradation. However, this mutant could still interact with the NMD and mRNA degradation factors and retained partial NMD activity. In addition, we found that the W73V mutant could not interact with translation initiation factors. Overexpression of W73V suppressed reporter mRNA translation in vitro and in vivo and reduced the level of a set of nascent proteins. These results reveal a residue of Y14 that confers cap-binding activity and is essential for Y14-mediated enhancement of translation. Finally, we demonstrated that Y14 may selectively and differentially modulate protein biosynthesis. PMID:26887951

ZnO nanoparticles and their acarbose-capped nanohybrids as inhibitors for human salivary amylase.

PubMed

Shaik, Firdoz; Kumar, Anil

2017-04-01

The authors report a controlled synthesis of biocompatible ZnO and acarbose-capped nanohybrids, and examined the inhibition activities of these nanosystems with human salivary α -amylase (HSA) activity. XRD measurements reveal ZnO present in wurtzite phase with hexagonal structure. The average size of ZnO particles for the two studied nanosystems was estimated to lie between 10 to 12 nm using Scherrer equation. These particles depict the onset of absorption at about 320 nm and the band-gap emission at about 370 nm, which are fairly blue shifted as compared with the bulk ZnO and have been understood due to the size quantisation effect. The inhibitory action of thioglycerol capped ZnO nanoparticles (SP1) and acarbose drug (used for diabetes type II) capped ZnO (SP2) for HSA was observed to 61 and72%, respectively. The inhibition activity of the SP1 alone was found to be very similar to that of acarbose and the coating of these particles with drug (SP2) demonstrated an enhancement in inhibition activity of the enzyme by about 30%. From the inhibition studies, it is confirmed that these nanosystems showed better inhibition activity at physiological temperature and pH. These nanosystems are projected to have potential applications in diabetes type II control.

Unified Modeling of Familial Mediterranean Fever and Cryopyrin Associated Periodic Syndromes.

PubMed

Bozkurt, Yasemin; Demir, Alper; Erman, Burak; Gül, Ahmet

2015-01-01

Familial mediterranean fever (FMF) and Cryopyrin associated periodic syndromes (CAPS) are two prototypical hereditary autoinflammatory diseases, characterized by recurrent episodes of fever and inflammation as a result of mutations in MEFV and NLRP3 genes encoding Pyrin and Cryopyrin proteins, respectively. Pyrin and Cryopyrin play key roles in the multiprotein inflammasome complex assembly, which regulates activity of an enzyme, Caspase 1, and its target cytokine, IL-1β. Overproduction of IL-1β by Caspase 1 is the main cause of episodic fever and inflammatory findings in FMF and CAPS. We present a unifying dynamical model for FMF and CAPS in the form of coupled nonlinear ordinary differential equations. The model is composed of two subsystems, which capture the interactions and dynamics of the key molecular players and the insults on the immune system. One of the subsystems, which contains a coupled positive-negative feedback motif, captures the dynamics of inflammation formation and regulation. We perform a comprehensive bifurcation analysis of the model and show that it exhibits three modes, capturing the Healthy, FMF, and CAPS cases. The mutations in Pyrin and Cryopyrin are reflected in the values of three parameters in the model. We present extensive simulation results for the model that match clinical observations.

Unified Modeling of Familial Mediterranean Fever and Cryopyrin Associated Periodic Syndromes

PubMed Central

Erman, Burak; Gül, Ahmet

2015-01-01

Familial mediterranean fever (FMF) and Cryopyrin associated periodic syndromes (CAPS) are two prototypical hereditary autoinflammatory diseases, characterized by recurrent episodes of fever and inflammation as a result of mutations in MEFV and NLRP3 genes encoding Pyrin and Cryopyrin proteins, respectively. Pyrin and Cryopyrin play key roles in the multiprotein inflammasome complex assembly, which regulates activity of an enzyme, Caspase 1, and its target cytokine, IL-1β. Overproduction of IL-1β by Caspase 1 is the main cause of episodic fever and inflammatory findings in FMF and CAPS. We present a unifying dynamical model for FMF and CAPS in the form of coupled nonlinear ordinary differential equations. The model is composed of two subsystems, which capture the interactions and dynamics of the key molecular players and the insults on the immune system. One of the subsystems, which contains a coupled positive-negative feedback motif, captures the dynamics of inflammation formation and regulation. We perform a comprehensive bifurcation analysis of the model and show that it exhibits three modes, capturing the Healthy, FMF, and CAPS cases. The mutations in Pyrin and Cryopyrin are reflected in the values of three parameters in the model. We present extensive simulation results for the model that match clinical observations. PMID:26161132

Robust Synthesis of Ciprofloxacin-Capped Metallic Nanoparticles and Their Urease Inhibitory Assay.

PubMed

Nisar, Muhammad; Khan, Shujaat Ali; Qayum, Mughal; Khan, Ajmal; Farooq, Umar; Jaafar, Hawa Z E; Zia-Ul-Haq, Muhammad; Ali, Rashid

2016-03-25

The fluoroquinolone antibacterial drug ciprofloxacin (cip) has been used to cap metallic (silver and gold) nanoparticles by a robust one pot synthetic method under optimized conditions, using NaBH₄ as a mild reducing agent. Metallic nanoparticles (MNPs) showed constancy against variations in pH, table salt (NaCl) solution, and heat. Capping with metal ions (Ag/Au-cip) has significant implications for the solubility, pharmacokinetics and bioavailability of fluoroquinolone molecules. The metallic nanoparticles were characterized by several techniques such as ultraviolet visible spectroscopy (UV), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) methods. The nanoparticles synthesized using silver and gold were subjected to energy dispersive X-ray tests in order to show their metallic composition. The NH moiety of the piperazine group capped the Ag/Au surfaces, as revealed by spectroscopic studies. The synthesized nanoparticles were also assessed for urease inhibition potential. Fascinatingly, both Ag-cip and Au-cip NPs exhibited significant urease enzyme inhibitory potential, with IC50 = 1.181 ± 0.02 µg/mL and 52.55 ± 2.3 µg/mL, compared to ciprofloxacin (IC50 = 82.95 ± 1.62 µg/mL). MNPs also exhibited significant antibacterial activity against selected bacterial strains.

Gilbert Damping Parameter in MgO-Based Magnetic Tunnel Junctions from First Principles

NASA Astrophysics Data System (ADS)

Tang, Hui-Min; Xia, Ke

2017-03-01

We perform a first-principles study of the Gilbert damping parameter (α ) in normal-metal/MgO-cap/ferromagnet/MgO-barrier/ferromagnetic magnetic tunnel junctions. The damping is enhanced by interface spin pumping, which can be parametrized by the spin-mixing conductance (G↑↓ ). The calculated dependence of Gilbert damping on the thickness of the MgO capping layer is consistent with experiment and indicates that the decreases in α with increasing thickness of the MgO capping layer is caused by suppression of spin pumping. Smaller α can be achieved by using a clean interface and alloys. For a thick MgO capping layer, the imaginary part of the spin-mixing conductance nearly equals the real part, and the large imaginary mixing conductance implies that the change in the frequency of ferromagnetic resonance can be observed experimentally. The normal-metal cap significantly affects the Gilbert damping.

The Role of Internet Addiction and Social Media Membership on University Students' Psychological Capital

ERIC Educational Resources Information Center

Simsek, Eylem; Sali, Jale Balaban

2014-01-01

How Internet addiction affects happiness of university students in terms of their cognitive and emotional resources was not adequately investigated. One of the inner resources of life satisfaction and happiness is defined as psychological capital (PsyCap), under the paradigm of positive psychology. PsyCap consists of four main sub-factors: hope,…

Meta-Analysis of the Impact of Positive Psychological Capital on Employee Attitudes, Behaviors, and Performance

ERIC Educational Resources Information Center

Avey, James B.; Reichard, Rebecca J.; Luthans, Fred; Mhatre, Ketan H.

2011-01-01

The positive core construct of psychological capital (or simply PsyCap), consisting of the psychological resources of hope, efficacy, resilience, and optimism, has recently been demonstrated to be open to human resource development (HRD) and performance management. The research stream on PsyCap has now grown to the point that a quantitative…

Psychophysics, flare, and neurosecretory function in human pain models: capsaicin versus electrically evoked pain.

PubMed

Geber, Christian; Fondel, Ricarda; Krämer, Heidrun H; Rolke, Roman; Treede, Rolfe-Detlef; Sommer, Claudia; Birklein, Frank

2007-06-01

Intradermal capsaicin injection (CAP) and electrical current stimulation (ES) are analyzed in respect to patterns and test-retest reliability of pain as well as sensory and neurosecretory changes. In 10 healthy subjects, 2x CAP (50 microg) and 2x ES (5 to 30 mA) were applied to the volar forearm. The time period between 2 identical stimulations was about 4 months. Pain ratings, areas of mechanical hyperalgesia, and allodynia were assessed. The intensity of sensory changes was quantified by using quantitative sensory testing. Neurogenic flare was assessed by using laser Doppler imaging. Calcitonin gene-related peptide (CGRP) release was quantified by dermal microdialysis in combination with an enzyme immunoassay. Time course and peak pain ratings were different between CAP and ES. Test-retest correlation was high (r > or = 0.73). Both models induced primary heat hyperalgesia and primary plus secondary pin-prick hyperalgesia. Allodynia occurred in about half of the subjects. Maximum flare sizes did not differ between CAP and ES, but flare intensities were higher for ES. Test-retest correlation was higher for flare sizes than for flare intensity. A significant CGRP release could only be measured after CAP. The different time courses of pain stimulation (CAP: rapidly decaying pain versus ES: pain plateau) led to different peripheral neurosecretory effects but induced similar central plasticity and hyperalgesia. The present study gives a detailed overview of psychophysical and neurosecretory characteristics induced by noxious stimulation with capsaicin and electrical current. We describe differences, similarities, and reproducibility of these human pain models. These data might help to interpret past and future results of human pain studies using experimental pain.

Lightweight Thermal Protection System for Atmospheric Entry

NASA Technical Reports Server (NTRS)

Stewart, David; Leiser, Daniel

2007-01-01

TUFROC (Toughened Uni-piece Fibrous Reinforced Oxidation-resistant Composite) has been developed as a new thermal protection system (TPS) material for wing leading edge and nose cap applications. The composite withstands temperatures up to 1,970 K, and consists of a toughened, high-temperature surface cap and a low-thermal-conductivity base, and is applicable to both sharp and blunt leading edge vehicles. This extends the possible application of fibrous insulation to the wing leading edge and/or nose cap on a hypersonic vehicle. The lightweight system comprises a treated carbonaceous cap composed of ROCCI (Refractory Oxidation-resistant Ceramic Carbon Insulation), which provides dimensional stability to the outer mold line, while the fibrous base material provides maximum thermal insulation for the vehicle structure.

Application of a simplified calculation for full-wave microtremor H/ V spectral ratio based on the diffuse field approximation to identify underground velocity structures

NASA Astrophysics Data System (ADS)

Wu, Hao; Masaki, Kazuaki; Irikura, Kojiro; Sánchez-Sesma, Francisco José

2017-12-01

Under the diffuse field approximation, the full-wave (FW) microtremor H/ V spectral ratio ( H/ V) is modeled as the square root of the ratio of the sum of imaginary parts of the Green's function of the horizontal components to that of the vertical one. For a given layered medium, the FW H/ V can be well approximated with only surface waves (SW) H/ V of the "cap-layered" medium which consists of the given layered medium and a new larger velocity half-space (cap layer) at large depth. Because the contribution of surface waves can be simply obtained by the residue theorem, the computation of SW H/ V of cap-layered medium is faster than that of FW H/ V evaluated by discrete wavenumber method and contour integration method. The simplified computation of SW H/ V was then applied to identify the underground velocity structures at six KiK-net strong-motion stations. The inverted underground velocity structures were used to evaluate FW H/ Vs which were consistent with the SW H/ Vs of corresponding cap-layered media. The previous study on surface waves H/ Vs proposed with the distributed surface sources assumption and a fixed Rayleigh-to-Love waves amplitude ratio for horizontal motions showed a good agreement with the SW H/ Vs of our study. The consistency between observed and theoretical spectral ratios, such as the earthquake motions of H/ V spectral ratio and spectral ratio of horizontal motions between surface and bottom of borehole, indicated that the underground velocity structures identified from SW H/ V of cap-layered medium were well resolved by the new method.[Figure not available: see fulltext.

Rapid wastage of the Hazen Plateau ice caps, northeastern Ellesmere Island, Nunavut, Canada

NASA Astrophysics Data System (ADS)

Serreze, Mark C.; Raup, Bruce; Braun, Carsten; Hardy, Douglas R.; Bradley, Raymond S.

2017-01-01

Two pairs of small stagnant ice bodies on the Hazen Plateau of northeastern Ellesmere Island, the St. Patrick Bay ice caps and the Murray and Simmons ice caps, are rapidly shrinking, and the remnants of the St. Patrick Bay ice caps are likely to disappear entirely within the next 5 years. Vertical aerial photographs of these Little Ice Age relics taken during August of 1959 show that the larger of the St. Patrick Bay ice caps had an area of 7.48 km2 and the smaller one 2.93 km2; the Murray and Simmons ice caps covered 4.37 and 7.45 km2 respectively. Outlines determined from ASTER satellite data for July 2016 show that, compared to 1959, the larger and the smaller of the St. Patrick Bay ice caps had both been reduced to only 5 % of their former area, with the Murray and Simmons ice caps faring better at 39 and 25 %, likely reflecting their higher elevation. Consistent with findings from other glaciological studies in the Queen Elizabeth Islands, ASTER imagery in conjunction with past GPS surveys documents a strikingly rapid wastage of the St. Patrick Bay ice caps over the last 15 years. These two ice caps shrank noticeably even between 2014 and 2015, apparently in direct response to the especially warm summer of 2015 over northeastern Ellesmere Island. The well-documented recession patterns of the Hazen Plateau ice caps over the last 55+ years offer an opportunity to examine the processes of plant recolonization of polar landscapes.

Risk of community-acquired pneumonia in patients with a diagnosis of pernicious anemia: a population-based retrospective cohort study.

PubMed

Almario, Christopher V; Metz, David C; Haynes, Kevin; Yang, Yu-Xiao

2015-11-01

Pernicious anemia (PA) is an autoimmune disease that causes achlorhydria or profound hypochlorhydria. We conducted a population-based study to determine whether individuals with PA are at an increased risk for community-acquired pneumonia (CAP). We performed a retrospective cohort study using The Health Improvement Network (THIN) from the UK (1993-2009). The eligible study cohort included individuals 18 years of age or older, with at least 1 year of THIN follow-up. The exposed group consisted of individuals with a diagnosis code for PA. The unexposed group consisted of individuals without a diagnosis of PA and was frequency matched with the exposed group with respect to age, sex, and practice site. Cox regression analysis was used to determine the hazard ratio with the 95% confidence interval for CAP associated with PA, accounting for a comprehensive list of potential confounders. The study included 13,605 individuals with PA and 50,586 non-PA individuals. The crude incidence rate of CAP was 9.4/1000 person-years for those with PA, versus 6.4/1000 person-years for those without PA. The multivariable adjusted hazard ratio for CAP associated with PA was 1.18 (95% confidence interval 1.08-1.29). In this large population-based cohort study, individuals with PA and presumed chronic achlorhydria were at an increased risk for CAP.

Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS).

PubMed

Kuemmerle-Deschner, Jasmin B; Ozen, Seza; Tyrrell, Pascal N; Kone-Paut, Isabelle; Goldbach-Mansky, Raphaela; Lachmann, Helen; Blank, Norbert; Hoffman, Hal M; Weissbarth-Riedel, Elisabeth; Hugle, Boris; Kallinich, Tilmann; Gattorno, Marco; Gul, Ahmet; Ter Haar, Nienke; Oswald, Marlen; Dedeoglu, Fatma; Cantarini, Luca; Benseler, Susanne M

2017-06-01

Cryopyrin-associated periodic syndrome (CAPS) is a rare, heterogeneous disease entity associated with NLRP3 gene mutations and increased interleukin-1 (IL-1) secretion. Early diagnosis and rapid initiation of IL-1 inhibition prevent organ damage. The aim of the study was to develop and validate diagnostic criteria for CAPS. An innovative process was followed including interdisciplinary team building, item generation: review of CAPS registries, systematic literature review, expert surveys, consensus conferences for item refinement, item reduction and weighting using 1000Minds decision software. Resulting CAPS criteria were tested in large cohorts of CAPS cases and controls using correspondence analysis. Diagnostic models were explored using sensitivity analyses. The international team included 16 experts. Systematic literature and registry review identified 33 CAPS-typical items; the consensus conferences reduced these to 14. 1000Minds exercises ranked variables based on importance for the diagnosis. Correspondence analysis determined variables consistently associated with the diagnosis of CAPS using 284 cases and 837 controls. Seven variables were significantly associated with CAPS (p<0.001). The best diagnosis model included: Raised inflammatory markers (C-reactive protein/serum amyloid A) plus ≥two of six CAPS-typical symptoms: urticaria-like rash, cold-triggered episodes, sensorineural hearing loss, musculoskeletal symptoms, chronic aseptic meningitis and skeletal abnormalities. Sensitivity was 81%, specificity 94%. It performed well for all CAPS subtypes and regardless of NLRP3 mutation. The novel approach integrated traditional methods of evidence synthesis with expert consensus, web-based decision tools and innovative statistical methods and may serve as model for other rare diseases. These criteria will enable a rapid diagnosis for children and adults with CAPS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Performance of two Aspergillus IgG EIA assays compared with the precipitin test in chronic and allergic aspergillosis.

PubMed

Baxter, C G; Denning, D W; Jones, A M; Todd, A; Moore, C B; Richardson, M D

2013-04-01

Detection of Aspergillus IgG antibodies is important in the diagnosis of chronic pulmonary aspergillosis and allergic bronchopulmonary aspergillosis. Immunoprecipitation techniques to detect these antibodies appear to lack sensitivity and accurate quantitation compared with enzyme immunoassays (EIA). This study assessed the performance of two commercial EIAs compared with counterimmunoelectrophoresis (CIE). This was a prospective cohort study of 175 adult patients with chronic or allergic pulmonary aspergillosis. Aspergillus IgG antibodies were detected using CIE, Phadia ImmunoCap Aspergillus IgG and Bio-Rad Platelia Aspergillus IgG. Inter-assay reproducibility was determined for each method and 25 patients had two serum samples analysed within a 6-month interval. When compared with CIE, both ImmunoCap and Platelia Aspergillus IgG had good sensitivity (97 and 93%, respectively) for detection of Aspergillus IgG antibodies. The level of agreement between the two EIAs for positive results was good, but the concentration of antibodies was not correlated between the tests or with CIE titre. ImmunoCap IgG inter-assay coefficient of variation was 5%, whereas Platelia IgG was 33%. Median ImmunoCap IgG values for CPA and allergic aspergillosis were 95 and 32 mg/L, respectively, whereas Platelia IgG values were >80 and 6 AU/mL. The direction of CIE titre change over 6 months was mirrored by ImmunoCap IgG levels in 92% of patients, and by Platelia IgG in 72% of patients. Both ImmunoCap and Platelia Aspergillus IgG EIAs are sensitive measures of Aspergillus IgG antibodies compared with CIE. However, ImmunoCap appears to have better reproducibility and may be more suitable for monitoring patient disease. © 2012 The Authors Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

Perennial water ice identified in the south polar cap of Mars

NASA Astrophysics Data System (ADS)

Bibring, Jean-Pierre; Langevin, Yves; Poulet, François; Gendrin, Aline; Gondet, Brigitte; Berthé, Michel; Soufflot, Alain; Drossart, Pierre; Combes, Michel; Bellucci, Giancarlo; Moroz, Vassili; Mangold, Nicolas; Schmitt, Bernard; OMEGA Team; Erard, S.; Forni, O.; Manaud, N.; Poulleau, G.; Encrenaz, T.; Fouchet, T.; Melchiorri, R.; Altieri, F.; Formisano, V.; Bonello, G.; Fonti, S.; Capaccioni, F.; Cerroni, P.; Coradini, A.; Kottsov, V.; Ignatiev, N.; Titov, D.; Zasova, L.; Pinet, P.; Sotin, C.; Hauber, E.; Hoffman, H.; Jaumann, R.; Keller, U.; Arvidson, R.; Mustard, J.; Duxbury, T.; Forget, F.

2004-04-01

The inventory of water and carbon dioxide reservoirs on Mars are important clues for understanding the geological, climatic and potentially exobiological evolution of the planet. From the early mapping observation of the permanent ice caps on the martian poles, the northern cap was believed to be mainly composed of water ice, whereas the southern cap was thought to be constituted of carbon dioxide ice. However, recent missions (NASA missions Mars Global Surveyor and Odyssey) have revealed surface structures, altimetry profiles, underlying buried hydrogen, and temperatures of the south polar regions that are thermodynamically consistent with a mixture of surface water ice and carbon dioxide. Here we present the first direct identification and mapping of both carbon dioxide and water ice in the martian high southern latitudes, at a resolution of 2km, during the local summer, when the extent of the polar ice is at its minimum. We observe that this south polar cap contains perennial water ice in extended areas: as a small admixture to carbon dioxide in the bright regions; associated with dust, without carbon dioxide, at the edges of this bright cap; and, unexpectedly, in large areas tens of kilometres away from the bright cap.

An empirical analysis of the multimarket contact theory in pharmaceutical markets.

PubMed

Coronado, Javier; Jiménez-Martín, Sergi; Marín, Pedro L

2014-07-01

Multimarket contact theory predicts that firms will optimally reduce prices in markets where collusive prices are sustainable and allocate the slack of the corresponding incentive compatibility to increase prices in markets where collusion is not sustainable. Binding price caps in collusive markets will have different effects over the multimarket contact mechanism depending on the severity of the cap. Setting a price cap close to the unregulated case will increase the size of the redistribution of market power whereas stronger regulation will even reduce prices in unregulated markets. Therefore, price regulations aiming at capping prices in a specific market will also affect markets that are not subject to specific mandatory price regulations. We find evidence of the theory predictions using information for nine OECD countries for pharmaceutical markets. Unregulated US markets are shown to respond to the redistribution effect; Canadian markets, known to be subject to soft price regulations, with respect to the former, are shown to be consistent with a stronger redistribution effect. EU markets and Japan are either consistent with the effect of a medium regulation or strong regulation. In this last case multimarket contact cannot explain prices, and these are expected to be lower compared to the unregulated benchmark.

TFIIH and P-TEFb Coordinate Transcription with Capping Enzyme Recruitment at Specific Genes in Fission Yeast

PubMed Central

Viladevall, Laia; St. Amour, Courtney V.; Rosebrock, Adam; Schneider, Susanne; Zhang, Chao; Allen, Jasmina J.; Shokat, Kevan M.; Schwer, Beate; Leatherwood, Janet K.; Fisher, Robert P.

2009-01-01

Summary Cyclin-dependent kinases (CDKs) are subunits of transcription factor (TF) IIH and positive transcription elongation factor b (P-TEFb). To define their functions, we mutated the TFIIH-associated kinase Mcs6 and P-TEFb homologs Cdk9 and Lsk1 of fission yeast, making them sensitive to bulky purine analogs. Selective inhibition of Mcs6 or Cdk9 blocks cell division, alters RNA polymerase (Pol) II carboxyl-terminal domain (CTD) phosphorylation and represses specific, overlapping subsets of transcripts. At a common target gene, both CDKs must be active for normal Pol II occupancy, and Spt5—a CDK substrate and regulator of elongation—accumulates disproportionately to Pol II when either kinase is inhibited. In contrast, Mcs6 activity is sufficient, and necessary, to recruit the Cdk9/Pcm1 (mRNA cap methyltransferase) complex. In vitro, phosphorylation of the CTD by Mcs6 stimulates subsequent phosphorylation by Cdk9. We propose that TFIIH primes the CTD and promotes recruitment of P-TEFb/Pcm1, serving to couple elongation and capping of select pre-mRNAs. PMID:19328067

Polyamidoamine dendrimers-capped carbon dots/Au nanocrystal nanocomposites and its application for electrochemical immunosensor.

PubMed

Gao, Qi; Han, Jingman; Ma, Zhanfang

2013-11-15

In this work, polyamidoamine dendrimers capped-carbon dots (PAMAM-CDs) were fabricated by one-step microwave assisted pyrolysis of citric acid (CA) and PAMAM, where the formation of CDs and the surface passivation were accomplished simultaneously. The obtained graphitic PAMAM-CDs, with abundant amine groups, were employed as reducing and capping agents for the formation of PAMAM-CDs/Au nanocrystal nanocomposites. The resulting nanocomposites exhibited excellent conductivity, stability and biocompatibility on the surface of electrode and were designed as an immobilized matrix for sensitive immunosensing of alpha-fetoprotein (AFP). The proposed immunosensor showed a wide linear detection range from 100 fg mL(-1) to 100 ng mL(-1). The detection limit for AFP was 0.025 pg mL(-1). Importantly, the immunosensor was evaluated for the analysis of clinical serum samples, obtaining a good correlation with enzyme-linked immunosorbent assay (ELISA). The results indicated that the immunosensor provided a possible application for the detection of AFP in clinical diagnosis. Copyright © 2013 Elsevier B.V. All rights reserved.

Activity of calcium activated protease in skeletal muscles and its changes in atrophy and stretch

NASA Technical Reports Server (NTRS)

Ellis, S.; Nagainis, P. A.

1984-01-01

The reduction of protein content in skeletal muscle undergoing disuse-induced atrophy is correlated with accelerated rates of protein degradation and reduced rates of protein synthesis (Goldspink, 1977). It is not known in what manner myofibers are partially disassembled during disuse atrophy to fibers of smaller diameter; nor is it known which proteases are responsible for this morphological change in contractile protein mass. Dayton and colleagues (1975) have suggested that the Ca(2+)-activated protease (CaP) may initiate myofibril degradation. The discovery of a form of CaP that is activatable by nano-molar concentrations of Ca(2+) indicates that CaP activity may be regulated by physiological concentrations of Ca(2+) (Mellgren, 1980). The enhancement of proteolysis by the Ca(2+) ionophore A23187, reported by Etlinger (1979), is consistent with a significant role for CaP in protein degradation. It was of interest, therefore, to measure the levels of CaP activity and the CaP inhibitor in extracts obtained from skeletal muscles of rat and chicken limbs undergoing disuse atrophy or stretch hypertrophy, respectively.

Impact of positive psychological capital on employee well-being over time.

PubMed

Avey, James B; Luthans, Fred; Smith, Ronda M; Palmer, Noel F

2010-01-01

The recently recognized core construct of psychological capital or PsyCap (consisting of the positive psychological resources of efficacy, hope, optimism, and resilience) has been demonstrated to be related to various employee attitudinal, behavioral, and performance outcomes. However, to date, the impact of this positive core construct over time and on important employee well-being outcomes has not been tested. This study meets this need by analyzing the relationship between a broad cross-section of employees' (N = 280) level of PsyCap and two measures of psychological well-being over time. The results indicated that employees' PsyCap was related to both measures of well-being and, importantly, that PsyCap explained additional variance in these well-being measures over time. The limitations, needed future research, and practical implications conclude the article.

Ultrastable BSA-capped gold nanoclusters with a polymer-like shielding layer against reactive oxygen species in living cells

NASA Astrophysics Data System (ADS)

Zhou, Wenjuan; Cao, Yuqing; Sui, Dandan; Guan, Weijiang; Lu, Chao; Xie, Jianping

2016-05-01

The prevalence of reactive oxygen species (ROS) production and the enzyme-containing intracellular environment could lead to the fluorescence quenching of bovine serum albumin (BSA)-capped gold nanoclusters (AuNCs). Here we report an efficient strategy to address this issue, where a polymer-like shielding layer is designed to wrap around the Au core to significantly improve the stability of AuNCs against ROS and protease degradation. The key of our design is to covalently incorporate a thiolated AuNC into the BSA-AuNC via carbodiimide-activated coupling, leading to the formation of a AuNC pair inside the cross-linked BSA molecule. The as-designed paired AuNCs in BSA (or BSA-p-AuNCs for short) show improved performances in living cells.The prevalence of reactive oxygen species (ROS) production and the enzyme-containing intracellular environment could lead to the fluorescence quenching of bovine serum albumin (BSA)-capped gold nanoclusters (AuNCs). Here we report an efficient strategy to address this issue, where a polymer-like shielding layer is designed to wrap around the Au core to significantly improve the stability of AuNCs against ROS and protease degradation. The key of our design is to covalently incorporate a thiolated AuNC into the BSA-AuNC via carbodiimide-activated coupling, leading to the formation of a AuNC pair inside the cross-linked BSA molecule. The as-designed paired AuNCs in BSA (or BSA-p-AuNCs for short) show improved performances in living cells. Electronic supplementary information (ESI) available: Detailed experimental materials, apparatus, experimental procedures and characterization data. See DOI: 10.1039/c6nr02178f

Controlling nonspecific protein adsorption in a plug-based microfluidic system by controlling interfacial chemistry using fluorous-phase surfactants.

PubMed

Roach, L Spencer; Song, Helen; Ismagilov, Rustem F

2005-02-01

Control of surface chemistry and protein adsorption is important for using microfluidic devices for biochemical analysis and high-throughput screening assays. This paper describes the control of protein adsorption at the liquid-liquid interface in a plug-based microfluidic system. The microfluidic system uses multiphase flows of immiscible fluorous and aqueous fluids to form plugs, which are aqueous droplets that are completely surrounded by fluorocarbon oil and do not come into direct contact with the hydrophobic surface of the microchannel. Protein adsorption at the aqueous-fluorous interface was controlled by using surfactants that were soluble in fluorocarbon oil but insoluble in aqueous solutions. Three perfluorinated alkane surfactants capped with different functional groups were used: a carboxylic acid, an alcohol, and a triethylene glycol group that was synthesized from commercially available materials. Using complementary methods of analysis, adsorption was characterized for several proteins (bovine serum albumin (BSA) and fibrinogen), including enzymes (ribonuclease A (RNase A) and alkaline phosphatase). These complementary methods involved characterizing adsorption in microliter-sized droplets by drop tensiometry and in nanoliter plugs by fluorescence microscopy and kinetic measurements of enzyme catalysis. The oligoethylene glycol-capped surfactant prevented protein adsorption in all cases. Adsorption of proteins to the carboxylic acid-capped surfactant in nanoliter plugs could be described by using the Langmuir model and tensiometry results for microliter drops. The microfluidic system was fabricated using rapid prototyping in poly(dimethylsiloxane) (PDMS). Black PDMS microfluidic devices, fabricated by curing a suspension of charcoal in PDMS, were used to measure the changes in fluorescence intensity more sensitively. This system will be useful for microfluidic bioassays, enzymatic kinetics, and protein crystallization, because it does not require surface modification during fabrication to control surface chemistry and protein adsorption.

Salivary Antigen-5/CAP Family Members Are Cu2+-dependent Antioxidant Enzymes That Scavenge O2⨪ and Inhibit Collagen-induced Platelet Aggregation and Neutrophil Oxidative Burst*

PubMed Central

Assumpção, Teresa C. F.; Ma, Dongying; Schwarz, Alexandra; Reiter, Karine; Santana, Jaime M.; Andersen, John F.; Ribeiro, José M. C.; Nardone, Glenn; Yu, Lee L.; Francischetti, Ivo M. B.

2013-01-01

The function of the antigen-5/CAP family of proteins found in the salivary gland of bloodsucking animals has remained elusive for decades. Antigen-5 members from the hematophagous insects Dipetalogaster maxima (DMAV) and Triatoma infestans (TIAV) were expressed and discovered to attenuate platelet aggregation, ATP secretion, and thromboxane A2 generation by low doses of collagen (<1 μg/ml) but no other agonists. DMAV did not interact with collagen, glycoprotein VI, or integrin α2β1. This inhibitory profile resembles the effects of antioxidants Cu,Zn-superoxide dismutase (Cu,Zn-SOD) in platelet function. Accordingly, DMAV was found to inhibit cytochrome c reduction by O2⨪ generated by the xanthine/xanthine oxidase, implying that it exhibits antioxidant activity. Moreover, our results demonstrate that DMAV blunts the luminescence signal of O2⨪ generated by phorbol 12-myristate 13-acetate-stimulated neutrophils. Mechanistically, inductively coupled plasma mass spectrometry and fluorescence spectroscopy revealed that DMAV, like Cu,Zn-SOD, interacts with Cu2+, which provides redox potential for catalytic removal of O2⨪. Notably, surface plasmon resonance experiments (BIAcore) determined that DMAV binds sulfated glycosaminoglycans (e.g. heparin, KD ∼100 nmol/liter), as reported for extracellular SOD. Finally, fractions of the salivary gland of D. maxima with native DMAV contain Cu2+ and display metal-dependent antioxidant properties. Antigen-5/CAP emerges as novel family of Cu2+-dependent antioxidant enzymes that inhibit neutrophil oxidative burst and negatively modulate platelet aggregation by a unique salivary mechanism. PMID:23564450

Regulation of Seed Germination in the Close Arabidopsis Relative Lepidium sativum: A Global Tissue-Specific Transcript Analysis1[C][W][OA

PubMed Central

Morris, Karl; Linkies, Ada; Müller, Kerstin; Oracz, Krystyna; Wang, Xiaofeng; Lynn, James R.; Leubner-Metzger, Gerhard; Finch-Savage, William E.

2011-01-01

The completion of germination in Lepidium sativum and other endospermic seeds (e.g. Arabidopsis [Arabidopsis thaliana]) is regulated by two opposing forces, the growth potential of the radicle (RAD) and the resistance to this growth from the micropylar endosperm cap (CAP) surrounding it. We show by puncture force measurement that the CAP progressively weakens during germination, and we have conducted a time-course transcript analysis of RAD and CAP tissues throughout this process. We have also used specific inhibitors to investigate the importance of transcription, translation, and posttranslation levels of regulation of endosperm weakening in isolated CAPs. Although the impact of inhibiting translation is greater, both transcription and translation are required for the completion of endosperm weakening in the whole seed population. The majority of genes expressed during this process occur in both tissues, but where they are uniquely expressed, or significantly differentially expressed between tissues, this relates to the functions of the RAD as growing tissue and the CAP as a regulator of germination through weakening. More detailed analysis showed that putative orthologs of cell wall-remodeling genes are expressed in a complex manner during CAP weakening, suggesting distinct roles in the RAD and CAP. Expression patterns are also consistent with the CAP being a receptor for environmental signals influencing germination. Inhibitors of the aspartic, serine, and cysteine proteases reduced the number of isolated CAPs in which weakening developed, and inhibition of the 26S proteasome resulted in its complete cessation. This indicates that targeted protein degradation is a major control point for endosperm weakening. PMID:21321254

Condensin II Regulates Interphase Chromatin Organization Through the Mrg-Binding Motif of Cap-H2

PubMed Central

Wallace, Heather A.; Klebba, Joseph E.; Kusch, Thomas; Rogers, Gregory C.; Bosco, Giovanni

2015-01-01

The spatial organization of the genome within the eukaryotic nucleus is a dynamic process that plays a central role in cellular processes such as gene expression, DNA replication, and chromosome segregation. Condensins are conserved multi-subunit protein complexes that contribute to chromosome organization by regulating chromosome compaction and homolog pairing. Previous work in our laboratory has shown that the Cap-H2 subunit of condensin II physically and genetically interacts with the Drosophila homolog of human MORF4-related gene on chromosome 15 (MRG15). Like Cap-H2, Mrg15 is required for interphase chromosome compaction and homolog pairing. However, the mechanism by which Mrg15 and Cap-H2 cooperate to maintain interphase chromatin organization remains unclear. Here, we show that Cap-H2 localizes to interband regions on polytene chromosomes and co-localizes with Mrg15 at regions of active transcription across the genome. We show that co-localization of Cap-H2 on polytene chromosomes is partially dependent on Mrg15. We have identified a binding motif within Cap-H2 that is essential for its interaction with Mrg15, and have found that mutation of this motif results in loss of localization of Cap-H2 on polytene chromosomes and results in partial suppression of Cap-H2-mediated compaction and homolog unpairing. Our data are consistent with a model in which Mrg15 acts as a loading factor to facilitate Cap-H2 binding to chromatin and mediate changes in chromatin organization. PMID:25758823

A front-end wafer-level microsystem packaging technique with micro-cap array

NASA Astrophysics Data System (ADS)

Chiang, Yuh-Min

2002-09-01

The back-end packaging process is the remaining challenge for the micromachining industry to commercialize microsystem technology (MST) devices at low cost. This dissertation presents a novel wafer level protection technique as a final step of the front-end fabrication process for MSTs. It facilitates improved manufacturing throughput and automation in package assembly, wafer level testing of devices, and enhanced device performance. The method involves the use of a wafer-sized micro-cap array, which consists of an assortment of small caps micro-molded onto a material with adjustable shapes and sizes to serve as protective structures against the hostile environments during packaging. The micro-cap array is first constructed by a micromachining process with micro-molding technique, then sealed to the device wafer at wafer level. Epoxy-based wafer-level micro cap array has been successfully fabricated and showed good compatibility with conventional back-end packaging processes. An adhesive transfer technique was demonstrated to seal the micro cap array with a MEMS device wafer. No damage or gross leak was observed while wafer dicing or later during a gross leak test. Applications of the micro cap array are demonstrated on MEMS, microactuators fabricated using CRONOS MUMPS process. Depending on the application needs, the micro-molded cap can be designed and modified to facilitate additional component functions, such as optical, electrical, mechanical, and chemical functions, which are not easily achieved in the device by traditional means. Successful fabrication of a micro cap array comprised with microlenses can provide active functions as well as passive protection. An optical tweezer array could be one possibility for applications of a micro cap with microlenses. The micro cap itself could serve as micro well for DNA or bacteria amplification as well.

The mediating role of psychological capital on the association between occupational stress and depressive symptoms among Chinese physicians: a cross-sectional study.

PubMed

Liu, Li; Chang, Ying; Fu, Jialiang; Wang, Jiana; Wang, Lie

2012-03-21

Although occupational stress is an identified predictor of depressive symptoms, the mechanism behind the association is not well understood. The purpose of this study was to examine how psychological capital (PsyCap), a positive psychological state, mediates the association between occupational stress and depressive symptoms among Chinese physicians. A cross-sectional survey was conducted in Liaoning Province, China, during September-October 2010. Self-administered questionnaires including items on depressive symptoms assessed by the Center for Epidemiologic Studies Depression Scale, occupational stress assessed by the effort-reward imbalance scale and PsyCap estimated by a 24-item Psychological Capital Questionnaire, together with age, gender, marital status and education were distributed to 1300 physicians employed in large general hospitals. The final sample consisted of 998 participants. Asymptotic and resampling strategies were used to examine how PsyCap mediates the association between occupational stress and depressive symptoms. Both the effort/reward ratio (ERR) and overcommitment were significantly associated with depressive symptoms among male and female physicians. There was a gender difference in the mediating role of PsyCap on the occupational stress-depressive symptoms association. For male physicians, PsyCap did not mediate the association between occupational stress and depressive symptoms. For female physicians, ERR and overcommitment were negatively associated with PsyCap, and PsyCap was negatively associated with depressive symptoms. As a result, PsyCap significantly mediated the associations of ERR and overcommitment with depressive symptoms. The proportion of PsyCap mediation was 19.07% for ERR, and 24.29% for overcommitment. PsyCap could be a positive resource for combating depressive symptoms in Chinese physicians. In addition to reducing occupational stress, PsyCap development should be included in depression prevention and treatment strategies, especially for female physicians.

Polyethylene versus cotton cap as an adjunct to body wrap in preterm infants.

PubMed

Shafie, Hashim; Syed Zakaria, Syed Zulkifli; Adli, Ali; Shareena, Ishak; Rohana, Jaafar

2017-07-01

Occlusive body wrap using polyethylene plastic applied immediately after birth had been shown to reduce hypothermia among preterm infants. Various adjunct methods have been studied in an attempt to further reduce the incidence of hypothermia. This study was conducted to determine whether polyethylene cap is more effective than cotton cap as an adjunct to polyethylene occlusive body wrap in reducing hypothermia in preterm infants. The subjects consisted of preterm infants 24-34 weeks' gestation born at Universiti Kebangsaan Malaysia Medical Centre. Infants were randomly assigned to NeoCap or control groups. Infants in both groups were wrapped in polyethylene sheets from the neck downwards immediately after birth without prior drying. Infants in the control group had their heads dried and subsequently covered with cotton caps while infants in the NeoCap group had polyethylene caps put on without drying. Axillary temperature was measured on admission to the neonatal intensive care unit (NICU), and after having been stabilized in the incubator. Among the 80 infants recruited, admission hypothermia (axillary temperature <36.5°C) was present in 37 (92.5%) and in 40 (100%) in the NeoCap and control groups, respectively. There was no significant difference in mean temperature on NICU admission between the two groups (35.3 vs 35.1°C, P = 0.36). Mean post-stabilization temperature, however, was significantly higher in the NeoCap group (36.0 vs 35.5°C, P = 0.01). Combined use of polyethylene body wrap and polyethylene cap was associated with a significantly higher mean post-stabilization temperature compared with polyethylene body wrap and cotton cap. © 2017 Japan Pediatric Society.

Cold-Cap Temperature Profile Comparison between the Laboratory and Mathematical Model

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

Dixon, Derek R.; Schweiger, Michael J.; Riley, Brian J.

2015-06-01

The rate of waste vitrification in an electric melter is connected to the feed-to-glass conversion process, which occurs in the cold cap, a layer of reacting feed on top of molten glass. The cold cap consists of two layers: a low temperature (~100°C – ~800°C) region of unconnected feed and a high temperature (~800°C – ~1100°C) region of foam with gas bubbles and cavities mixed in the connected glass melt. A recently developed mathematical model describes the effect of the cold cap on glass production. For verification of the mathematical model, a laboratory-scale melter was used to produce a coldmore » cap that could be cross-sectioned and polished in order to determine the temperature profile related to position in the cold cap. The cold cap from the laboratory-scale melter exhibited an accumulation of feed ~400°C due to radiant heat from the molten glass creating dry feed conditions in the melter, which was not the case in the mathematical model where wet feed conditions were calculated. Through the temperature range from ~500°C – ~1100°C, there was good agreement between the model and the laboratory cold cap. Differences were observed between the two temperature profiles due to the temperature of the glass melts and the lack of secondary foam, large cavities, and shrinkage of the primary foam bubbles upon the cooling of the laboratory-scale cold cap.« less

High-Latitude Ionospheric Imaging using Canadian High Arctic Ionospheric Network (CHAIN)

NASA Astrophysics Data System (ADS)

Meziane, K.; Jayachandran, P. T.; Hamza, A. M.; MacDougall, J. W.

2013-12-01

Understanding the polar cap dynamics is a fundamental problem in solar-terrestrial physics; any breakthroughs would have to take into account the interactions that take place at the interfaces between the Solar Wind and the Magnetosphere and between the latter and the ionosphere, respectively. Over the past decade a significant number of ground-based GPS receivers and digital ionosondes have been deployed in the polar cap and auroral region. This deployment has allowed the harvest of much needed data, otherwise not available, which in turn helps understand the dynamics of the polar ionospheric regions. A technique, used consistently by researchers in the field, consists of inverting the Total Electron Content (TEC) along the ray path obtained from a system of GPS receivers. In the present study, a combination of tomography and ionosonde data from the CHAIN network is used to examine the dynamics of polar cap patches. First, the TEC derived from GPS receivers through tomographic reconstruction is directly compared with ionosonde data. The comparison includes periods of quite and disturbed geomagnetic activity. We then use the vertical density profiles derived from the CHAIN ionosondes as initial seeds for the reconstruction of the tomographic images of the polar cap regions. Precise electron density peaks obtained through the tomographic reconstruction fall within a range that is consistent with direct CHAIN measurements when certain conditions are met. An assessment of the performance of the resulting combination of GPS and ionosonde data is performed, and conclusions are presented.

Kinetics of ozonation. 4. Reactions of ozone with. cap alpha. -tocopherol and oleate and linoleate esters in carbon tetrachloride and in aqueous micellar solvents

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

Giamalva, D.H.; Church, D.F.; Pryor, W.A.

1986-10-15

Vitamin E (..cap alpha..-tocopherol; ..cap alpha..-T) is known to protect animals against the deleterious effects of ozone in polluted air; one such effect is the ozone-initiated autooxidation of polyunsaturated fatty acids (PUFA) that occur in membranes. In order to assess the possibility of a direct reaction of ozone with ..cap alpha..-T competing with the very fast ozone-PUFA reaction, we have measured the rates of reaction of ozone with ..cap alpha..-T, oleic acid, and linoleic acid. I CCl/sub 4/ as solvent, ..cap alpha..-T reacts with ozone with a rate constant of about 5500 M/sup -1/ s/sup -1/; methyl oleate and methylmore » linoleate react 2 orders of magnitude faster. In aqueous micellar solutions the rate constants for ..cap alpha..-T and the fatty acids are more similar. The k for the ozone/..cap alpha..-T reaction is about 1 x 10/sup 6/ M/sup -1/ s/sup -1/ at pH 7, but decreases as the solution becomes more acidic; the k's for oleic acid and linoleic acid are ca. 1 x 10/sup 6/ M/sup -1/ s/sup -1/ and exhibit no significant pH dependence. Since the ratio of fatty acids to ..cap alpha..-T in membranes is typically at least 100-1000 to 1, we conclude that the direct reaction of ozone with ..cap alpha..-T is unlikely. Thus, the protection that vitamin E provides to animals breathing ozone-containing air must result from vitamin E acting as a free radical scavenger. We have also detected the ..cap alpha..-tocopheroxyl radical as an intermediate from the reaction of ozone with ..cap alpha..-T both in CCl/sub 4/ and aqueous micelles using electron spin resonance spectroscopy. The authors suggest that the observation of this intermediate is consistent with an initial electron transfer from ..cap alpha..-T to ozone.« less

The Incidence Rate and Economic Burden of Community-Acquired Pneumonia in a Working-Age Population

PubMed Central

Broulette, Jonah; Yu, Holly; Pyenson, Bruce; Iwasaki, Kosuke; Sato, Reiko

2013-01-01

Background Community-acquired pneumonia (CAP) is frequently associated with the very young and the elderly but is a largely underrecognized burden among working-age adults. Although the burden of CAP among the elderly has been established, there are limited data on the economic burden of CAP in the employed population. Objective To assess the economic impact of CAP in US working-age adults from an employer perspective by estimating the incidence rate and costs of healthcare, sick time, and short-term disability for this patient population. Methods This retrospective cohort study is based on data from 2 Truven Health Analytics databases. The study population consisted of commercially insured active employees aged 18 to 64 years, early retirees aged <65 years, and adult dependents of both cohorts. CAP was identified using medical claims with pneumonia diagnosis codes during the 2009 calendar year. Incidence rate, episode level, and annual costs were stratified by age and by risk based on the presence of comorbidities. Descriptive statistics were used to compare healthcare (ie, medical and pharmacy) costs, sick time, and short-term disability costs between the cohorts with and without CAP. Linear regression was used to estimate the average annual incremental healthcare cost in employed patients with inpatient or outpatient CAP versus individuals without CAP. Results Study eligibility was met by 12,502,017 employed individuals, including 123,920 with CAP and 12,378,097 without CAP; the overall incidence rate of CAP was 10.6 per 1000 person-years. Among individuals with and without CAP, the costs of healthcare, sick time, and short-term disability increased with advancing age and with higher risk status. The mean annual healthcare costs were $20,961 for patients with CAP and $3783 for individuals without CAP. Overall, the mean costs of sick time and short-term disability were $1129 and $1016, respectively, in active employees with CAP, and $853 and $322, respectively, in their counterparts without CAP. Compared with individuals without CAP, the average annual incremental healthcare cost ranged from $39,889 to $113,837 for inpatient management of patients with CAP and from $4170 to $31,524 for outpatient management of patients with CAP, depending on the risk level. Conclusions CAP is a common and costly infection among working-age individuals, especially in patients with comorbidities. Prevention strategies, such as influenza and pneumococcal vaccination, that target working-age adults with underlying medical conditions may be the most valuable in reducing the morbidity and costs associated with CAP. PMID:24991378

The incidence rate and economic burden of community-acquired pneumonia in a working-age population.

PubMed

Broulette, Jonah; Yu, Holly; Pyenson, Bruce; Iwasaki, Kosuke; Sato, Reiko

2013-09-01

Community-acquired pneumonia (CAP) is frequently associated with the very young and the elderly but is a largely underrecognized burden among working-age adults. Although the burden of CAP among the elderly has been established, there are limited data on the economic burden of CAP in the employed population. To assess the economic impact of CAP in US working-age adults from an employer perspective by estimating the incidence rate and costs of healthcare, sick time, and short-term disability for this patient population. This retrospective cohort study is based on data from 2 Truven Health Analytics databases. The study population consisted of commercially insured active employees aged 18 to 64 years, early retirees aged <65 years, and adult dependents of both cohorts. CAP was identified using medical claims with pneumonia diagnosis codes during the 2009 calendar year. Incidence rate, episode level, and annual costs were stratified by age and by risk based on the presence of comorbidities. Descriptive statistics were used to compare healthcare (ie, medical and pharmacy) costs, sick time, and short-term disability costs between the cohorts with and without CAP. Linear regression was used to estimate the average annual incremental healthcare cost in employed patients with inpatient or outpatient CAP versus individuals without CAP. Study eligibility was met by 12,502,017 employed individuals, including 123,920 with CAP and 12,378,097 without CAP; the overall incidence rate of CAP was 10.6 per 1000 person-years. Among individuals with and without CAP, the costs of healthcare, sick time, and short-term disability increased with advancing age and with higher risk status. The mean annual healthcare costs were $20,961 for patients with CAP and $3783 for individuals without CAP. Overall, the mean costs of sick time and short-term disability were $1129 and $1016, respectively, in active employees with CAP, and $853 and $322, respectively, in their counterparts without CAP. Compared with individuals without CAP, the average annual incremental healthcare cost ranged from $39,889 to $113,837 for inpatient management of patients with CAP and from $4170 to $31,524 for outpatient management of patients with CAP, depending on the risk level. CAP is a common and costly infection among working-age individuals, especially in patients with comorbidities. Prevention strategies, such as influenza and pneumococcal vaccination, that target working-age adults with underlying medical conditions may be the most valuable in reducing the morbidity and costs associated with CAP.

A multi-point perspective on the formation of polar cap arcs: kinetic modeling and observations by Cluster and TIMED

NASA Astrophysics Data System (ADS)

de Keyser, J. M.; Maggiolo, R.; Echim, M.; Simon, C.; Zhang, Y.; Trotignon, J.

2010-12-01

On April 1st, 2004 the GUVI imager onboard the TIMED spacecraft spots an isolated and elongated polar cap arc. Simultaneously, the Cluster spacecraft detects an isolated upflowing ion beam above the polar cap. Cluster observations show that the ions are accelerated upward by a quasi-stationary electric field. The field-aligned potential drop is estimated to about 600 V and the upflowing ions are accompanied by a tenuous population of isotropic protons with a temperature of about 300eV. The footprint of the magnetic field line on which the Cluster spacecraft are situated, is located just outside the GUVI field of view in the prolongation of the polar cap arc. This suggests that the upflowing ion beam and the polar cap arc may be different signatures of the same phenomenon, as suggested by a recent statistical study of polar cap ion beams using Cluster data. We use Cluster observations at high altitude as input to a quasi-stationary magnetosphere-ionosphere (MI) coupling model. Using a Knight-type current-voltage relationship and the current continuity at the topside ionosphere, the model computes the energy spectrum of precipitating electrons at ionospheric altitudes corresponding to the generator electric field observed by Cluster. The MI coupling model provides a field-aligned potential drop in agreement with Cluster observations of upflowing ions and a spatial scale of the polar cap arc consistent with the optical observations by TIMED. The energy spectrum of the precipitating electrons provided by the model is introduced as input to the Trans4 ionospheric transport code. This 1-D model, based on Boltzmann's kinetic formalism, takes into account ionospheric processes like photoionisation and electron/proton precipitation, and computes the optical and UV emissions due to precipitating electrons. The emission rates provided by the Trans4 code are then compared to the optical observations by TIMED. Data and modeling results are consistent with quasi-static acceleration of precipitating magnetospheric electrons. We also discuss possible implications of our modeling results for optical observations of polar cap arcs.

Technical feasibility of patient-friendly screening and treatment of digestive disease by remote control robotic capsule endoscopes via the internet.

PubMed

Ohta, Hidetoshi; Kawashima, Makoto

2014-01-01

A few types of steerable capsule endoscopes have been proposed but disappointingly their systems were not applicable to common endoscopic treatment or pathological diagnosis. This study validates the possibility of treatment and biopsy by using an internet-linked (wireless control via the internet) robotic capsule endoscope (iRoboCap). iRoboCap consisted of three parts: an imaging unit, a movement control unit and a therapeutic tool unit. Two types of iRoboCaps were designed, one was a submarine type (iRoboCap-S) and the other was an amphibious type (iRoboCap-A). They were remotely and wirelessly steered by a portable tablet device using Bluetooth and via the internet. The success rates of biopsy or clipping were evaluated in a phantom. Although the two prototypes have various problems that need improving, we hope that our robotic and wireless innovations have opened the door to new endoscopic procedures and will pioneer various new applications in medicine.

Risk of Community-Acquired Pneumonia in Patients with a Diagnosis of Pernicious Anemia: A Population-Based Retrospective Cohort Study

PubMed Central

Almario, Christopher V.; Metz, David C.; Haynes, Kevin; Yang, Yu-Xiao

2015-01-01

Objective Pernicious anemia (PA) is an autoimmune disease that causes achlorhydria or profound hypochlorhydria. We conducted a population-based study to determine whether individuals with PA are at increased risk for community-acquired pneumonia (CAP). Methods We performed a retrospective cohort study using The Health Improvement Network (THIN) from the United Kingdom (1993 to 2009). The eligible study cohort included individuals 18 years of age or older and with at least 1 year of THIN follow-up. The exposed group consisted of individuals with a diagnosis code for PA. The unexposed group consisted of individuals without a diagnosis of PA and was frequency matched with the exposed group with respect to age, sex, and practice site. Cox regression analysis was used to determine the hazard ratio (HR) with 95% confidence interval (CI) for CAP associated with PA, accounting for a comprehensive list of potential confounders. Results The study included 13,605 individuals with PA and 50,586 non-PA subjects. The crude incidence rate of CAP was 9.4 per 1000 person-years for those with PA, versus 6.4 per 1000 person-years for those without PA. The multivariable adjusted HR for CAP associated with PA was 1.18, 95% CI 1.08 – 1.29. Conclusions In this large population-based cohort study, individuals with PA and presumed chronic achlorhydria were at increased risk for CAP. PMID:26225868

CisSERS: Customizable in silico sequence evaluation for restriction sites

DOE PAGES

Sharpe, Richard M.; Koepke, Tyson; Harper, Artemus; ...

2016-04-12

High-throughput sequencing continues to produce an immense volume of information that is processed and assembled into mature sequence data. Here, data analysis tools are urgently needed that leverage the embedded DNA sequence polymorphisms and consequent changes to restriction sites or sequence motifs in a high-throughput manner to enable biological experimentation. CisSERS was developed as a standalone open source tool to analyze sequence datasets and provide biologists with individual or comparative genome organization information in terms of presence and frequency of patterns or motifs such as restriction enzymes. Predicted agarose gel visualization of the custom analyses results was also integrated tomore » enhance the usefulness of the software. CisSERS offers several novel functionalities, such as handling of large and multiple datasets in parallel, multiple restriction enzyme site detection and custom motif detection features, which are seamlessly integrated with real time agarose gel visualization. Using a simple fasta-formatted file as input, CisSERS utilizes the REBASE enzyme database. Results from CisSERSenable the user to make decisions for designing genotyping by sequencing experiments, reduced representation sequencing, 3’UTR sequencing, and cleaved amplified polymorphic sequence (CAPS) molecular markers for large sample sets. CisSERS is a java based graphical user interface built around a perl backbone. Several of the applications of CisSERS including CAPS molecular marker development were successfully validated using wet-lab experimentation. Here, we present the tool CisSERSand results from in-silico and corresponding wet-lab analyses demonstrating that CisSERS is a technology platform solution that facilitates efficient data utilization in genomics and genetics studies.« less

CisSERS: Customizable in silico sequence evaluation for restriction sites

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

Sharpe, Richard M.; Koepke, Tyson; Harper, Artemus

High-throughput sequencing continues to produce an immense volume of information that is processed and assembled into mature sequence data. Here, data analysis tools are urgently needed that leverage the embedded DNA sequence polymorphisms and consequent changes to restriction sites or sequence motifs in a high-throughput manner to enable biological experimentation. CisSERS was developed as a standalone open source tool to analyze sequence datasets and provide biologists with individual or comparative genome organization information in terms of presence and frequency of patterns or motifs such as restriction enzymes. Predicted agarose gel visualization of the custom analyses results was also integrated tomore » enhance the usefulness of the software. CisSERS offers several novel functionalities, such as handling of large and multiple datasets in parallel, multiple restriction enzyme site detection and custom motif detection features, which are seamlessly integrated with real time agarose gel visualization. Using a simple fasta-formatted file as input, CisSERS utilizes the REBASE enzyme database. Results from CisSERSenable the user to make decisions for designing genotyping by sequencing experiments, reduced representation sequencing, 3’UTR sequencing, and cleaved amplified polymorphic sequence (CAPS) molecular markers for large sample sets. CisSERS is a java based graphical user interface built around a perl backbone. Several of the applications of CisSERS including CAPS molecular marker development were successfully validated using wet-lab experimentation. Here, we present the tool CisSERSand results from in-silico and corresponding wet-lab analyses demonstrating that CisSERS is a technology platform solution that facilitates efficient data utilization in genomics and genetics studies.« less

Enzyme-Controlled Nanodevice for Acetylcholine-Triggered Cargo Delivery Based on Janus Au-Mesoporous Silica Nanoparticles.

PubMed

Llopis-Lorente, Antoni; Díez, Paula; de la Torre, Cristina; Sánchez, Alfredo; Sancenón, Félix; Aznar, Elena; Marcos, María D; Martínez-Ruíz, Paloma; Martínez-Máñez, Ramón; Villalonga, Reynaldo

2017-03-28

This work reports a new gated nanodevice for acetylcholine-triggered cargo delivery. We prepared and characterized Janus Au-mesoporous silica nanoparticles functionalized with acetylcholinesterase on the Au face and with supramolecular β-cyclodextrin:benzimidazole inclusion complexes as caps on the mesoporous silica face. The nanodevice is able to selectively deliver the cargo in the presence of acetylcholine via enzyme-mediated acetylcholine hydrolysis, locally lowering the pH and opening the supramolecular gate. Given the key role played by ACh and its relation with Parkinson's disease and other nervous system diseases, we believe that these findings could help design new therapeutic strategies. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

An extracellular enzyme synthesizes narrow-sized silver nanoparticles in both water and methanol

NASA Astrophysics Data System (ADS)

Rai, Tripti; Panda, Debashis

2015-03-01

Cellulase reduces silver ions in both aqueous and methanolic media yielding stable narrow-sized silver nanoparticles (Ag-NP) at room temperature. The synthesized nanoparticles have been characterized by various spectroscopic, microscopic methods. The redox potentials of tyrosine residues and protein backbone play an instrumental role to reduce the metal ions. The average size of nanoparticles formed in aqueous medium is of 5.04 ± 3.50 nm. Post-synthesis of Ag-NP secondary structure of enzyme is completely lost whereas upon incubation with chemically synthesized Ag-NP a significant gain in secondary structure is observed. Cellulase as a capping ligand stabilizes the silver nanoparticles even in methanol.

A Point Mutation in the Exon Junction Complex Factor Y14 Disrupts Its Function in mRNA Cap Binding and Translation Enhancement.

PubMed

Chuang, Tzu-Wei; Lee, Kuo-Ming; Lou, Yuan-Chao; Lu, Chia-Chen; Tarn, Woan-Yuh

2016-04-15

Eukaryotic mRNA biogenesis involves a series of interconnected steps mediated by RNA-binding proteins. The exon junction complex core protein Y14 is required for nonsense-mediated mRNA decay (NMD) and promotes translation. Moreover, Y14 binds the cap structure of mRNAs and inhibits the activity of the decapping enzyme Dcp2. In this report, we show that an evolutionarily conserved tryptophan residue (Trp-73) of Y14 is critical for its binding to the mRNA cap structure. A Trp-73 mutant (W73V) bound weakly to mRNAs and failed to protect them from degradation. However, this mutant could still interact with the NMD and mRNA degradation factors and retained partial NMD activity. In addition, we found that the W73V mutant could not interact with translation initiation factors. Overexpression of W73V suppressed reporter mRNA translation in vitro and in vivo and reduced the level of a set of nascent proteins. These results reveal a residue of Y14 that confers cap-binding activity and is essential for Y14-mediated enhancement of translation. Finally, we demonstrated that Y14 may selectively and differentially modulate protein biosynthesis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

A decision tool for selecting trench cap designs

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

Paige, G.B.; Stone, J.J.; Lane, L.J.

1995-12-31

A computer based prototype decision support system (PDSS) is being developed to assist the risk manager in selecting an appropriate trench cap design for waste disposal sites. The selection of the {open_quote}best{close_quote} design among feasible alternatives requires consideration of multiple and often conflicting objectives. The methodology used in the selection process consists of: selecting and parameterizing decision variables using data, simulation models, or expert opinion; selecting feasible trench cap design alternatives; ordering the decision variables and ranking the design alternatives. The decision model is based on multi-objective decision theory and uses a unique approach to order the decision variables andmore » rank the design alternatives. Trench cap designs are evaluated based on federal regulations, hydrologic performance, cover stability and cost. Four trench cap designs, which were monitored for a four year period at Hill Air Force Base in Utah, are used to demonstrate the application of the PDSS and evaluate the results of the decision model. The results of the PDSS, using both data and simulations, illustrate the relative advantages of each of the cap designs and which cap is the {open_quotes}best{close_quotes} alternative for a given set of criteria and a particular importance order of those decision criteria.« less

Hospital admissions of adults with community-acquired pneumonia in Portugal between 2000 and 2009.

PubMed

Froes, Filipe; Diniz, António; Mesquita, Margarida; Serrado, Margarida; Nunes, Baltazar

2013-05-01

Recent studies in the USA and northern Europe have shown an increase in community-acquired pneumonia (CAP). In southern Europe, this increase has not yet been documented. We carried out a retrospective analysis from encoded information from the Portuguese database for hospital admissions that included all individuals aged ≥18 years, with a primary diagnosis of pneumonia, who were discharged between 2000 and 2009. We excluded patients infected with HIV, individuals immunocompromised as a result of anti-cancer or immunosuppressive treatment, and transplant recipients. Of the 294 027 admissions for CAP, 56% were male. The mean age was 73.1 years and the median age 77 years. Between 2000 and 2009, there was a 5% increase in the average age of patients admitted with CAP. Admissions for CAP represented 3.7% of total admissions of adult patients. The average annual rate of hospital admissions for adults with CAP was 3.61 per 1000 total population, rising to 13.4 for those aged ≥65 years. Between 2000-2004 and 2005-2009 the average annual rate of hospital admission for CAP per 1000 population increased by 28.2%. Hospital admissions for CAP in Portugal increased between 2000 and 2009. It has grown consistently over time, varying according to age with males over-represented.

The water footprint of Milan.

PubMed

Vanham, D; Bidoglio, G

2014-01-01

This study quantifies the water footprint of consumption (WFcons) and production (WFprod) of Milan. The current WFcons amounts to 6,139 l/cap/d (a volume of 2.93 km(3) annually), of which 52 l/cap/d (1%) is attributed to domestic water, 448 l/cap/d (7%) to the consumption of industrial products and 5,639 l/cap/d (92%) to the consumption of agricultural products. The WFprod is 52 l/cap/d. Milan is thus a net virtual water importer, predominantly through the import of agricultural products. These are produced outside city borders, both in Italy and abroad. This shows the dependency of city dwellers on water resources from other river basins. In addition, the WFcons for a healthy diet (based on Mediterranean Food-Based Dietary Guidelines) and a vegetarian diet are analysed. The current Milanese diet consists of too much sugar, crop oils, meat, animal fats, milk and milk products and not enough cereals, rice, potatoes, vegetables and fruit. The latter two diets result in substantial WFcons reductions: -29% (to 4,339 l/cap/d) for a healthy diet and -41% (to 3,631 l/cap/d) for a vegetarian diet. Indeed, a lot of water could be saved by Milan citizens through a change in their diet. A sustainable city should account for its impacts beyond its borders.

Transport properties of nanocomposite and its simulation with L-R-C circuit

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

Gangopadhyay, Arnab, E-mail: agangulyphysics@gmail.com; Sarkar, Aditi, E-mail: agangulyphysics@gmail.com; Sarkar, A., E-mail: agangulyphysics@gmail.com

2014-04-24

The nano particles are represented in this communication by L-R-C equivalent circuit. The dc current voltage characteristics (CVC) of the proposed circuit have simulated using Circuit-Maker ® 2000. Experimental investigation on ZnO nano-composite with capping material gum acacia shows similar CVC. NPs are represented by C-R combinations to manifest the Coulomb blockade effect of a quantum dot. The capping material is represented by an inductor along with a resistance in series. Nine NPs with capping matrix are simulated. The dc current voltage characteristics (CVC) and gross feature of polarization nature obtained by experiment and simulation study are consistent.

Discovery of aliphatic-chain hydroxamates containing indole derivatives with potent class I histone deacetylase inhibitory activities.

PubMed

Chao, Shi-Wei; Chen, Liang-Chieh; Yu, Chia-Chun; Liu, Chang-Yi; Lin, Tony Eight; Guh, Jih-Hwa; Wang, Chen-Yu; Chen, Chun-Yung; Hsu, Kai-Cheng; Huang, Wei-Jan

2018-01-01

Histone deacetylase (HDAC) is a validated drug target for various diseases. This study combined indole recognition cap with SAHA, an FDA-approved HDAC inhibitor used to treat cutaneous T-cell lymphoma (CTCL). The structure activity relationship of the resulting compounds that inhibited HDAC was disclosed as well. Some compounds exhibited much stronger inhibitory activities than SAHA. We identified two meta-series compounds 6j and 6k with a two-carbon linker had IC 50 values of 3.9 and 4.5 nM for HDAC1, respectively. In contrast, the same oriented compounds with longer carbon chain linkers showed weaker inhibition. The result suggests that the linker chain length greatly contributed to enzyme inhibitory potency. In addition, comparison of enzyme-inhibiting activity between the compounds and SAHA showed that compounds 6j and 6k displayed higher inhibiting activity for class I (HDAC1, -2, -3 and -8). The molecular docking and structure analysis revealed structural differences with the inhibitor cap and metal-binding regions between the HDAC isozymes that affect interactions with the inhibitors and play a key role for selectivity. Further biological evaluation showed multiple cellular effects associated with compounds 6j- and 6k-induced HDAC inhibitory activity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Polar cap arcs from the magnetosphere to the ionosphere: kinetic modelling and observations by Cluster and TIMED

NASA Astrophysics Data System (ADS)

Maggiolo, R.; Echim, M.; Wedlund, C. Simon; Zhang, Y.; Fontaine, D.; Lointier, G.; Trotignon, J.-G.

2012-02-01

On 1 April 2004 the GUVI imager onboard the TIMED spacecraft spots an isolated and elongated polar cap arc. About 20 min later, the Cluster satellites detect an isolated upflowing ion beam above the polar cap. Cluster observations show that the ions are accelerated upward by a quasi-stationary electric field. The field-aligned potential drop is estimated to about 700 V and the upflowing ions are accompanied by a tenuous population of isotropic protons with a temperature of about 500 eV. The magnetic footpoints of the ion outflows observed by Cluster are situated in the prolongation of the polar cap arc observed by TIMED GUVI. The upflowing ion beam and the polar cap arc may be different signatures of the same phenomenon, as suggested by a recent statistical study of polar cap ion beams using Cluster data. We use Cluster observations at high altitude as input to a quasi-stationary magnetosphere-ionosphere (MI) coupling model. Using a Knight-type current-voltage relationship and the current continuity at the topside ionosphere, the model computes the energy spectrum of precipitating electrons at the top of the ionosphere corresponding to the generator electric field observed by Cluster. The MI coupling model provides a field-aligned potential drop in agreement with Cluster observations of upflowing ions and a spatial scale of the polar cap arc consistent with the optical observations by TIMED. The computed energy spectrum of the precipitating electrons is used as input to the Trans4 ionospheric transport code. This 1-D model, based on Boltzmann's kinetic formalism, takes into account ionospheric processes such as photoionization and electron/proton precipitation, and computes the optical and UV emissions due to precipitating electrons. The emission rates provided by the Trans4 code are compared to the optical observations by TIMED. They are similar in size and intensity. Data and modelling results are consistent with the scenario of quasi-static acceleration of electrons that generate a polar cap arc as they precipitate in the ionosphere. The detailed observations of the acceleration region by Cluster and the large scale image of the polar cap arc provided by TIMED are two different features of the same phenomenon. Combined together, they bring new light on the configuration of the high-latitude magnetosphere during prolonged periods of Northward IMF. Possible implications of the modelling results for optical observations of polar cap arcs are also discussed.

MGS TES observations of the water vapor above the seasonal and perennial ice caps during northern spring and summer

NASA Astrophysics Data System (ADS)

Pankine, Alexey A.; Tamppari, Leslie K.; Smith, Michael D.

2010-11-01

We report on new retrievals of water vapor column abundances from the Mars Global Surveyor (MGS) Thermal Emission Spectrometer (TES) data. The new retrievals are from the TES nadir data taken above the 'cold' surface areas in the North polar region ( Tsurf < 220 K, including seasonal frost and permanent ice cap) during spring and summer seasons, where retrievals were not performed initially. Retrievals are possible (with some modifications to the original algorithm) over cold surfaces overlaid by sufficiently warm atmosphere. The retrieved water vapor column abundances are compared to the column abundances observed by other spacecrafts in the Northern polar region during spring and summer and good agreement is found. We detect an annulus of water vapor growing above the edge of the retreating seasonal cap during spring. The formation of the vapor annulus is consistent with the previously proposed mechanism for water cycling in the polar region, according to which vapor released by frost sublimation during spring re-condenses on the retreating seasonal CO 2 cap. The source of the vapor in the vapor annulus, according to this model, is the water frost on the surface of the CO 2 at the retreating edge of the cap and the frost on the ground that is exposed by the retreating cap. Small contribution from regolith sources is possible too, but cannot be quantified based on the TES vapor data alone. Water vapor annulus exhibits interannual variability, which we attribute to variations in the atmospheric temperature. We propose that during spring and summer the water ice sublimation is retarded by high relative humidity of the local atmosphere, and that higher atmospheric temperatures lead to higher vapor column abundances by increasing the water holding capacity of the atmosphere. Since the atmospheric temperatures are strongly influenced by the atmospheric dust content, local dust storms may be controlling the release of vapor into the polar atmosphere. Water vapor abundances above the residual polar cap also exhibit noticeable interannual variability. In some years abundances above the cap are lower than the abundances outside of the cap, consistent with previous observations, while in the other years the abundances above the cap are higher or similar to abundances outside of the cap. We speculate that the differences may be due to weaker off-cap transport in the latter case, keeping more vapor closer to the source at the surface of the residual cap. Despite the large observed variability in water vapor column abundances in the Northern polar region during spring and summer, the latitudinal distribution of the vapor mass in the atmosphere is very similar during the summer season. If the variability in vapor abundances is caused by the variability of vapor sources across the residual cap then this would mean that they annually contribute relatively little vapor mass to significantly affect the vapor mass budget. Alternatively this may suggest that the vapor variability is caused by the variability of the polar atmospheric circulation. The new water vapor retrievals should be useful in tuning the Global Circulation Models of the martian water cycle.

Inhaled concentrated ambient particles are associated with hematologic and bronchoalveolar lavage changes in canines.

PubMed Central

Clarke, R W; Coull, B; Reinisch, U; Catalano, P; Killingsworth, C R; Koutrakis, P; Kavouras, I; Murthy, G G; Lawrence, J; Lovett, E; Wolfson, J M; Verrier, R L; Godleski, J J

2000-01-01

Pulmonary inflammatory and hematologic responses of canines were studied after exposure to concentrated ambient particles (CAPs) using the Harvard ambient particle concentrator (HAPC). For pulmonary inflammatory studies, normal dogs were exposed in pairs to either CAPs or filtered air (paired studies) for 6 hr/day on 3 consecutive days. For hematologic studies, dogs were exposed for 6 hr/day for 3 consecutive days with one receiving CAPs while the other was simultaneously exposed to filtered air; crossover of exposure took place the following week (crossover studies). Physicochemical characterization of CAPs exposure samples included measurements of particle mass, size distribution, and composition. No statistical differences in biologic responses were found when all CAPs and all sham exposures were compared. However, the variability in biologic response was considerably higher with CAPs exposure. Subsequent exploratory graphical analyses and mixed linear regression analyses suggested associations between CAPs constituents and biologic responses. Factor analysis was applied to the compositional data from paired and crossover experiments to determine elements consistently associated with each other in CAPs samples. In paired experiments, four factors were identified; in crossover studies, a total of six factors were observed. Bronchoalveolar lavage (BAL) and hematologic data were regressed on the factor scores. Increased BAL neutrophil percentage, total peripheral white blood cell (WBC) counts, circulating neutrophils, and circulating lymphocytes were associated with increases in the aluminum/silicon factor. Increased circulating neutrophils and increased BAL macrophages were associated with the vanadium/nickel factor. Increased BAL neutrophils were associated with the bromine/lead factor when only the compositional data from the third day of CAPs exposure were used. Significant decreases in red blood cell counts and hemoglobin levels were correlated with the sulfur factor. BAL or hematologic parameters were not associated with increases in total CAPs mass concentration. These data suggest that CAPs inhalation is associated with subtle alterations in pulmonary and systemic cell profiles, and specific components of CAPs may be responsible for these biologic responses. PMID:11133399

Mapping of p140Cap Phosphorylation Sites: The EPLYA and EGLYA Motifs Have a Key Role in Tyrosine Phosphorylation and Csk Binding, and Are Substrates of the Abl Kinase

PubMed Central

Sharma, Nanaocha; Grasso, Silvia; Russo, Isabella; Jensen, Ole N.; Cabodi, Sara; Turco, Emilia; Di Stefano, Paola; Defilippi, Paola

2013-01-01

Protein phosphorylation tightly regulates specific binding of effector proteins that control many diverse biological functions of cells (e. g. signaling, migration and proliferation). p140Cap is an adaptor protein, specifically expressed in brain, testis and epithelial cells, that undergoes phosphorylation and tunes its interactions with other regulatory molecules via post-translation modification. In this work, using mass spectrometry, we found that p140Cap is in vivo phosphorylated on tyrosine (Y) within the peptide GEGLpYADPYGLLHEGR (from now on referred to as EGLYA) as well as on three serine residues. Consistently, EGLYA has the highest score of in silico prediction of p140Cap phosphorylation. To further investigate the p140Cap function, we performed site specific mutagenesis on tyrosines inserted in EGLYA and EPLYA, a second sequence with the same highest score of phosphorylation. The mutant protein, in which both EPLYA/EGLYA tyrosines were converted to phenylalanine, was no longer tyrosine phosphorylated, despite the presence of other tyrosine residues in p140Cap sequence. Moreover, this mutant lost its ability to bind the C-terminal Src kinase (Csk), previously shown to interact with p140Cap by Far Western analysis. In addition, we found that in vitro and in HEK-293 cells, the Abelson kinase is the major kinase involved in p140Cap tyrosine phosphorylation on the EPLYA and EGLYA sequences. Overall, these data represent an original attempt to in vivo characterise phosphorylated residues of p140Cap. Elucidating the function of p140Cap will provide novel insights into its biological activity not only in normal cells, but also in tumors. PMID:23383002

Transient Receptor Potential Vanilloid 1 Expression Mediates Capsaicin-Induced Cell Death.

PubMed

Ramírez-Barrantes, Ricardo; Córdova, Claudio; Gatica, Sebastian; Rodriguez, Belén; Lozano, Carlo; Marchant, Ivanny; Echeverria, Cesar; Simon, Felipe; Olivero, Pablo

2018-01-01

The transient receptor potential (TRP) ion channel family consists of a broad variety of non-selective cation channels that integrate environmental physicochemical signals for dynamic homeostatic control. Involved in a variety of cellular physiological processes, TRP channels are fundamental to the control of the cell life cycle. TRP channels from the vanilloid (TRPV) family have been directly implicated in cell death. TRPV1 is activated by pain-inducing stimuli, including inflammatory endovanilloids and pungent exovanilloids, such as capsaicin (CAP). TRPV1 activation by high doses of CAP (>10 μM) leads to necrosis, but also exhibits apoptotic characteristics. However, CAP dose-response studies are lacking in order to determine whether CAP-induced cell death occurs preferentially via necrosis or apoptosis. In addition, it is not known whether cytosolic Ca 2+ and mitochondrial dysfunction participates in CAP-induced TRPV1-mediated cell death. By using TRPV1-transfected HeLa cells, we investigated the underlying mechanisms involved in CAP-induced TRPV1-mediated cell death, the dependence of CAP dose, and the participation of mitochondrial dysfunction and cytosolic Ca 2+ increase. Together, our results contribute to elucidate the pathophysiological steps that follow after TRPV1 stimulation with CAP. Low concentrations of CAP (1 μM) induce cell death by a mechanism involving a TRPV1-mediated rapid and transient intracellular Ca 2+ increase that stimulates plasma membrane depolarization, thereby compromising plasma membrane integrity and ultimately leading to cell death. Meanwhile, higher doses of CAP induce cell death via a TRPV1-independent mechanism, involving a slow and persistent intracellular Ca 2+ increase that induces mitochondrial dysfunction, plasma membrane depolarization, plasma membrane loss of integrity, and ultimately, cell death.

Targeted in-vivo computed tomography (CT) imaging of tissue ACE using concentrated lisinopril-capped gold nanoparticle solutions

NASA Astrophysics Data System (ADS)

Daniel, Marie-Christine; Aras, Omer; Smith, Mark F.; Nan, Anjan; Fleiter, Thorsten

2010-04-01

The development of cardiac and pulmonary fibrosis have been associated with overexpression of angiotensin-converting enzyme (ACE). Moreover, ACE inhibitors, such as lisinopril, have shown a benificial effect for patients diagnosed with heart failure or systemic hypertension. Thus targeted imaging of the ACE is of crucial importance for monitoring of the tissue ACE activity as well as the treatment efficacy in heart failure. In this respect, lisinopril-capped gold nanoparticles were prepared to provide a new type of probe for targeted molecular imaging of ACE by tuned K-edge computed tomography (CT) imaging. Concentrated solutions of these modified gold nanoparticles, with a diameter around 16 nm, showed high contrast in CT imaging. These new targeted imaging agents were thus used for in vivo imaging on rat models.

Atomically resolved calcium phosphate coating on a gold substrate.

PubMed

Metoki, Noah; Baik, Sung-Il; Isheim, Dieter; Mandler, Daniel; Seidman, David N; Eliaz, Noam

2018-05-10

Some articles have revealed that the electrodeposition of calcium phosphate (CaP) coatings entails a precursor phase, similarly to biomineralization in vivo. The chemical composition of the initial layer and its thickness are, however, still arguable, to the best of our knowledge. Moreover, while CaP and electrodeposition of metal coatings have been studied utilizing atom-probe tomography (APT), the electrodeposition of CaP ceramics has not been heretofore studied. Herein, we present an investigation of the CaP deposition on a gold substrate. Using APT and transmission electron microscopy (TEM) it is found that a mixture of phases, which could serve as transient precursor phases to hydroxyapatite (HAp), can be detected. The thickness of these phases is tens of nanometers, and they consist of amorphous CaP (ACP), dibasic calcium phosphate dihydrate (DCPD), and octacalcium phosphate (OCP). This demonstrates the value of using atomic-resolved characterization techniques for identifying the precursor phases. It also indicates that the kinetics of their transformation into the more stable HAp is not too fast to enable their observation. The coating gradually displays higher Ca/P atomic ratios, a porous nature, and concomitantly a change in its density.

Selective inhibition by chloramphenicol of pregnenolone-16. cap alpha. -carbonitrile-inducible rat liver cytochrome P-450 isozymes

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

Graves, P.E.; Kaminsky, L.S.; Halpert, J.

Pregnenolone-16 ..cap alpha..-carbonitrile (PCN) has been shown to induce, in male rats, cytochrome P-450 isozymes responsible for the formation of R-10-hydroxywarfarin and R-dehydrowarfarin. Antibodies to the major PCN-inducible isozyme (PB/PCN-E) inhibit both activities in microsomal preparations. Recently the authors have shown that PCN treatment of female rats also induces the formation of both R-warfarin metabolites. However, in both sexes chloramphenicol (CAP) treatment selectively inhibits only the rate of formation of the R-dehydrowarfarin. A decrease in microsomal P-450 content occurs after in vivo administration of CAP to PCN-treated rats of both sexes. This is in contrast to the lack of effectmore » of CAP on P-450 levels in phenobarbital-treated rats. Covalent binding of /sup 14/C-CAP to microsomal protein in vitro was increased 3 to 4-fold following PCN treatment. Chromatographic evidences suggests the presence of at least two PCN-induced isozymes of similar molecular weights in both male and female rat liver microsomes. These data are consistent with the multiplicity of PCN-inducible P-450 in rat liver.« less

Distribution and chloramphenicol in the bovine genital tract and pharmacokinetic studies of florfenicol in cattle

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

Bretzlaff, K.N.

1986-01-01

The objectives were to investigate selected aspects of the distribution of chloramphenicol (CAP) in the bovine genital tract and to conduct preliminary pharmacologic studies with florfenicol (FLO), a fluorinated analogue of thiamphenicol, in cattle. After 8 hours' continuous intravenous (IV) infusion of CAP to 7 postpartum cows, steady state plasma-to-genital tissue ratios of CAP were approximately 3. After intrauterine infusion of 20 mg CAP/kg to 3 postpartum cows, approximately 40% of the dose was absorbed into the bloodstream. Tissue concentrations were high at 8 hour postdosing in tissues lining the uterine lumen but were below desired therapeutic concentrations in themore » myometrium of 2 of the cows. Eighty cows with retained fetal membranes (RFM) were assigned to receive on the following treatments: (1) removal of membranes only; (2) removal plus CAP; (3) nonremoval; (4) nonremoval plus CAP. CAP treatment consisted of 5 g administered IU twice daily for 3 days. The majority of cows in all groups acquired endometritis, although CAP reduced the prevalence and severity of the disease. A quantitative assay for FLO in plasma was developed and validated on a high performance liquid chromatographic (HPLC) system. The pharmacokinetics of FLO determined after IV administration of 50 mg FLO/kg to 5 cows were best described by a three-compartment model. FLO was approximately 18% bound to plasma proteins as determined by equilibrium dialysis and ultrafiltration. In an in vitro system, 5, 125, or 1000 ug/ml of CAP had no effect on neutrophils from 6 cows.« less

Using Ice Predictions to Guide Submarines

DTIC Science & Technology

2016-01-01

the Arctic Cap Nowcast/ Forecast System (ACNFS) in September 2013. The ACNFS consists of a coupled ice -ocean model that assimilates available real...of the ice cover. The age of the sea ice serves as an indicator of its physical properties including surface roughness, melt pond coverage, and...the Arctic Cap Nowcast/Forecast System (ACNFS). Ice thickness is in meters for 11 September 2015. Thickness ranges from zero to five meters as shown

Kinetics of Cold-Cap Reactions for Vitrification of Nuclear Waste Glass Based on Simultaneous Differential Scanning Calorimetry - Thermogravimetry (DSC-TGA) and Evolved Gas Analysis (EGA)

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

Rodriguez, Carmen P.; Pierce, David A.; Schweiger, Michael J.

2013-12-03

For vitrifying nuclear waste glass, the feed, a mixture of waste with glass-forming and modifying additives, is charged onto the cold cap that covers 90-100% of the melt surface. The cold cap consists of a layer of reacting molten glass floating on the surface of the melt in an all-electric, continuous glass melter. As the feed moves through the cold cap, it undergoes chemical reactions and phase transitions through which it is converted to molten glass that moves from the cold cap into the melt pool. The process involves a series of reactions that generate multiple gases and subsequent massmore » loss and foaming significantly influence the mass and heat transfers. The rate of glass melting, which is greatly influenced by mass and heat transfers, affects the vitrification process and the efficiency of the immobilization of nuclear waste. We studied the cold-cap reactions of a representative waste glass feed using both the simultaneous differential scanning calorimetry thermogravimetry (DSC-TGA) and the thermogravimetry coupled with gas chromatography-mass spectrometer (TGA-GC-MS) as complementary tools to perform evolved gas analysis (EGA). Analyses from DSC-TGA and EGA on the cold-cap reactions provide a key element for the development of an advanced cold-cap model. It also helps to formulate melter feeds for higher production rate.« less

Incomplete caries removal and indirect pulp capping in primary molars: a randomized controlled trial.

PubMed

Bressani, Ana Eliza Lemes; Mariath, Adriela Azevedo Souza; Haas, Alex Nogueira; Garcia-Godoy, Franklin; de Araujo, Fernando Borba

2013-08-01

To compare the effect of incomplete caries removal (ICR) and indirect pulp capping (IPC) with calcium hydroxide (CH) or an inert material (wax) on color, consistency and contamination of the remaining dentin of primary molars. This double-blind, parallel-design, randomized controlled trial included 30 children presenting one primary molar with deep caries lesion. Children were randomly assigned after ICR to receive IPC with CH or wax. All teeth were then restored with resin composite. Baseline dentin color and consistency were evaluated after ICR, and dentin samples were collected for contamination analyses using scanning electron microscopy. After 3 months, restorations were removed and the three parameters were re-evaluated. In both groups, dentin became significantly darker after 3 months. No cases of yellow dentin were observed after 3 months with CH compared to 33.3% of the wax cases (P < 0.05). A statistically significant difference over time was observed only for CH regarding consistency. CH stimulated a dentin hardening process in a statistically higher number of cases than wax (86.7% vs. 33.3%; P = 0.008). Contamination changed significantly over time in CH and wax without significant difference between groups. It was concluded that CH and wax arrested the carious process of the remaining carious dentin after indirect pulp capping, but CH showed superior dentin color and consistency after 3 months.

Hydrogen and deuterium in the local interstellar medium

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

Murthy, J.N.

1987-01-01

This work reports on the results of a series of IUE observations of interstellar HI and DI Ly..cap alpha.. absorption against the chromospheric Ly..cap alpha.. emission of the nearby late-type stars ..cap alpha.. Cen B(1.3 pc), epsilon Eri (3.3 pc), Procyon (3.5 pc), Altair (5.1 pc), Capella (13.2 pc), and HR 1099 (33 pc). The density, velocity dispersion, and bulk velocity of the neutral hydrogen along the line of sight to each of these stars was derived. Lower limits were placed on the deuterium-to-hydrogen (D/H) ratio towards the same stars. These IUE results are generally consistent with previous observations ofmore » the same stars with the Copernicus satellite showing that this modeling procedure is independent of stellar variations over a period of several years. The HI absorption profile towards Altair shows a broad saturated core and steep line wings, consistent with a multicomponent interstellar medium in that direction. The bulk velocities towards the other stars are consistent with a bulk flow from the approximate direction of the galactic center but do show local variations from a uniform flow, possibly indicating a complicated velocity structure even in the solar neighborhood. Interstellar deuterium is detected towards every star except Altair and the derived values for the D/H ratio are consistent with those previously found with Copernicus.« less

Immunogenicity and immunoprotection of porcine circovirus type 2 (PCV2) Cap protein displayed by Lactococcus lactis.

PubMed

Li, Peng-Cheng; Qiao, Xu-Wen; Zheng, Qi-Sheng; Hou, Ji-Bo

2016-01-27

The capsid (Cap) protein, an important immunoprotective protein of porcine circovirus type 2 (PCV2), was expressed on the cell surface of the Gram-positive food-grade bacterium, Lactococcus lactis. Cap protein was fused to the peptidoglycan binding domain (known as the protein anchor domain, PA) of the lactococcal AcmA cell-wall hydrolase. The Cap protein fusion was non-covalently rebound to the surface of non-genetically modified, non-living high-binder L. lactis cells (designated Gram-positive enhancer matrix (GEM) particles). Expression of the recombinant GEM-displaying capsid protein (GEM-PA-Cap) was verified by Western blotting and immunofluorescence and transmission electron microscopy assays. To evaluate the immunogenicity of the recombinant Cap protein (rCap), 20 PCV2-seronegative piglets were immunized with the GEM-PA-Cap subunit vaccine, GEM alone, or phosphate-buffered saline (PBS, challenge control and empty control). Each group consisted of five piglets. The results showed that the level of PCV2-specific antibodies in piglets immunized with the GEM-PA-Cap subunit vaccine was significantly higher than that of the piglets immunized with GEM alone or the control group at all the time points post-vaccination (P<0.01). After challenge with the PCV2 wild-type strain, piglets that received the GEM-PA-Cap subunit vaccine showed significantly higher average daily weight gain (DWG) and shorter fever duration than the other two groups (P<0.001). Furthermore, a significant reduction in the gross lung lesion scores and lymph node lesion scores was noted in the GEM-PA-Cap-immunized group compared with the scores of the GEM or PBS-treated group (P<0.01). The results suggest that recombinant rCap displayed by L. lactis GEM particles provided the piglets with significant immunoprotection from PCV2-associated disease. Thus, the novel GEM-PA-Cap subunit vaccine has potential to be considered an effective and safe candidate vaccine against PCV2 infection in piglets. Copyright © 2015. Published by Elsevier Ltd.

Fos Expression in Rat Brain During Depletion-Induced Thirst and Salt Appetite

NASA Technical Reports Server (NTRS)

Thunhorst, R. L.; Xu, Z.; Cicha, M. Z.; Zardetto-Smith, A. M.; Johnson, A. K.

1998-01-01

The expression of Fos protein (Fos immunoreactivity, Fos-ir) was mapped in the brain of rats subjected to an angiotensin-dependent model of thirst and salt appetite. The physiological state associated with water and sodium ingestion was produced by the concurrent subcutaneous administration of the diuretic furosemide (10 mg/kg) and a low dose of the angiotensin-converting enzyme (ACE) inhibitor captopril (5 mg/kg; Furo/Cap treatment). The animals were killed 2 h posttreatment, and the brains were processed for Fos-ir to assess neural activation. Furo/Cap treatment significantly increased Fos-ir density above baseline levels both in structures of the lamina terminalis and hypothalamus known to mediate the actions of ANG 2 and in hindbrain regions associated with blood volume and pressure regulation. Furo/Cap treatment also typically increased Fos-ir density in these structures above levels observed after administration of furosemide or captopril separately. Fos-ir was reduced to a greater extent in forebrain than in hindbrain areas by a dose of captopril (100 mg/kg sc) known to block the actions of ACE in the brain. The present work provides further evidence that areas of lamina terminalis subserve angiotensin-dependent thirst and salt appetite.

Reversible methylation of m6Am in the 5′ cap controls mRNA stability

PubMed Central

Mauer, Jan; Luo, Xiaobing; Blanjoie, Alexandre; Jiao, Xinfu; Grozhik, Anya V.; Patil, Deepak P.; Linder, Bastian; Pickering, Brian F.; Vasseur, Jean-Jacques; Chen, Qiuying; Gross, Steven S.; Elemento, Olivier; Debart, Françoise; Kiledjian, Megerditch; Jaffrey, Samie R.

2017-01-01

Internal bases in mRNA can be subjected to modifications that influence the fate of mRNA in cells. One of the most prevalent modified bases is found at the 5′ end of mRNA, at the first encoded nucleotide adjacent to the 7-methylguanosine cap. Here we show that this nucleotide, N6,2′-O-dimethyladenosine (m6Am), is a reversible modification that influences cellular mRNA fate. Using a transcriptome-wide map of m6Am we find that m6Am-initiated transcripts are markedly more stable than mRNAs that begin with other nucleotides. We show that the enhanced stability of m6Am-initiated transcripts is due to resistance to the mRNA-decapping enzyme DCP2. Moreover, we find that m6Am is selectively demethylated by fat mass and obesity-associated protein (FTO). FTO preferentially demethylates m6Am rather than N6-methyladenosine (m6A), and reduces the stability of m6Am mRNAs. Together, these findings show that the methylation status of m6Am in the 5′ cap is a dynamic and reversible epitranscriptomic modification that determines mRNA stability. PMID:28002401

Effects of chronic plus acute prolonged stress on measures of coping style, anxiety, and evoked HPA-axis reactivity.

PubMed

Roth, Megan K; Bingham, Brian; Shah, Aparna; Joshi, Ankur; Frazer, Alan; Strong, Randy; Morilak, David A

2012-11-01

Exposure to psychological trauma is the precipitating factor for PTSD. In addition, a history of chronic or traumatic stress exposure is a predisposing risk factor. We have developed a Chronic plus Acute Prolonged Stress (CAPS) treatment for rats that models some of the characteristics of stressful events that can lead to PTSD in humans. We have previously shown that CAPS enhances acute fear responses and impairs extinction of conditioned fear. Further, CAPS reduced the expression of glucocorticoid receptors in the medial prefrontal cortex. In this study we examined the effects of CAPS exposure on behavioral stress coping style, anxiety-like behaviors, and acute stress reactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Male Sprague-Dawley rats were exposed to CAPS treatment, consisting of chronic intermittent cold stress (4 °C, 6 h/day, 14 days) followed on day 15 by a single 1-h session of sequential acute stressors (social defeat, immobilization, swim). After CAPS or control treatment, different groups were tested for shock probe defensive burying, novelty suppressed feeding, or evoked activation of adrenocorticotropic hormone (ACTH) and corticosterone release by an acute immobilization stress. CAPS resulted in a decrease in active burying behavior and an increase in immobility in the shock probe test. Further, CAPS-treated rats displayed increases in the latency to feed in the novelty suppressed feeding test, despite an increase in food intake in the home cage. CAPS treatment also reduced the HPA response to a subsequent acute immobilization stress. These results further validate CAPS treatment as a rat model of relevance to PTSD, and together with results reported previously, suggest that CAPS impairs fear extinction, shifts coping behavior from an active to a more passive strategy, increases anxiety, and alters HPA reactivity, resembling many aspects of human PTSD. Copyright © 2012 Elsevier Ltd. All rights reserved.

The mediating role of psychological capital on the association between occupational stress and depressive symptoms among Chinese physicians: a cross-sectional study

PubMed Central

2012-01-01

Background Although occupational stress is an identified predictor of depressive symptoms, the mechanism behind the association is not well understood. The purpose of this study was to examine how psychological capital (PsyCap), a positive psychological state, mediates the association between occupational stress and depressive symptoms among Chinese physicians. Methods A cross-sectional survey was conducted in Liaoning Province, China, during September–October 2010. Self-administered questionnaires including items on depressive symptoms assessed by the Center for Epidemiologic Studies Depression Scale, occupational stress assessed by the effort–reward imbalance scale and PsyCap estimated by a 24-item Psychological Capital Questionnaire, together with age, gender, marital status and education were distributed to 1300 physicians employed in large general hospitals. The final sample consisted of 998 participants. Asymptotic and resampling strategies were used to examine how PsyCap mediates the association between occupational stress and depressive symptoms. Results Both the effort/reward ratio (ERR) and overcommitment were significantly associated with depressive symptoms among male and female physicians. There was a gender difference in the mediating role of PsyCap on the occupational stress–depressive symptoms association. For male physicians, PsyCap did not mediate the association between occupational stress and depressive symptoms. For female physicians, ERR and overcommitment were negatively associated with PsyCap, and PsyCap was negatively associated with depressive symptoms. As a result, PsyCap significantly mediated the associations of ERR and overcommitment with depressive symptoms. The proportion of PsyCap mediation was 19.07% for ERR, and 24.29% for overcommitment. Conclusions PsyCap could be a positive resource for combating depressive symptoms in Chinese physicians. In addition to reducing occupational stress, PsyCap development should be included in depression prevention and treatment strategies, especially for female physicians. PMID:22436106

Metagenomic mining for thermostable esterolytic enzymes uncovers a new family of bacterial esterases.

PubMed

Zarafeta, Dimitra; Moschidi, Danai; Ladoukakis, Efthymios; Gavrilov, Sergey; Chrysina, Evangelia D; Chatziioannou, Aristotelis; Kublanov, Ilya; Skretas, Georgios; Kolisis, Fragiskos N

2016-12-19

Biocatalysts exerting activity against ester bonds have a broad range of applications in modern biotechnology. Here, we have identified a new esterolytic enzyme by screening a metagenomic sample collected from a hot spring in Kamchatka, Russia. Biochemical characterization of the new esterase, termed EstDZ2, revealed that it is highly active against medium chain fatty acid esters at temperatures between 25 and 60 °C and at pH values 7-8. The new enzyme is moderately thermostable with a half-life of more than six hours at 60 °C, but exhibits exquisite stability against high concentrations of organic solvents. Phylogenetic analysis indicated that EstDZ2 is likely an Acetothermia enzyme that belongs to a new family of bacterial esterases, for which we propose the index XV. One distinctive feature of this new family, is the presence of a conserved GHSAG catalytic motif. Multiple sequence alignment, coupled with computational modelling of the three-dimensional structure of EstDZ2, revealed that the enzyme lacks the largest part of the "cap" domain, whose extended structure is characteristic for the closely related Family IV esterases. Thus, EstDZ2 appears to be distinct from known related esterolytic enzymes, both in terms of sequence characteristics, as well as in terms of three-dimensional structure.

Effects of prosodically modulated sub-phonetic variation on lexical competition.

PubMed

Salverda, Anne Pier; Dahan, Delphine; Tanenhaus, Michael K; Crosswhite, Katherine; Masharov, Mikhail; McDonough, Joyce

2007-11-01

Eye movements were monitored as participants followed spoken instructions to manipulate one of four objects pictured on a computer screen. Target words occurred in utterance-medial (e.g., Put the cap next to the square) or utterance-final position (e.g., Now click on the cap). Displays consisted of the target picture (e.g., a cap), a monosyllabic competitor picture (e.g., a cat), a polysyllabic competitor picture (e.g., a captain) and a distractor (e.g., a beaker). The relative proportion of fixations to the two types of competitor pictures changed as a function of the position of the target word in the utterance, demonstrating that lexical competition is modulated by prosodically conditioned phonetic variation.

Communication: Distinguishing between bulk and interface-enhanced crystallization in nanoscale films of amorphous solid water.

PubMed

Yuan, Chunqing; Smith, R Scott; Kay, Bruce D

2017-01-21

The crystallization of amorphous solid water (ASW) nanoscale films was investigated using reflection absorption infrared spectroscopy. Two ASW film configurations were studied. In one case the ASW film was deposited on top of and capped with a decane layer ("sandwich" configuration). In the other case, the ASW film was deposited on top of a decane layer and not capped ("no cap" configuration). Crystallization of ASW films in the "sandwich" configuration is about eight times slower than in the "no cap." Selective placement of an isotopic layer (5% D 2 O in H 2 O) at various positions in an ASW (H 2 O) film was used to determine the crystallization mechanism. In the "sandwich" configuration, the crystallization kinetics were independent of the isotopic layer placement whereas in the "no cap" configuration the closer the isotopic layer was to the vacuum interface, the earlier the isotopic layer crystallized. These results are consistent with a mechanism whereby the decane overlayer suppresses surface nucleation and provide evidence that the observed ASW crystallization in "sandwich" films is the result of uniform bulk nucleation.

Sequestration by IFIT1 Impairs Translation of 2′O-unmethylated Capped RNA

PubMed Central

Lacerda, Livia; Benda, Christian; Holze, Cathleen; Eberl, Christian H.; Mann, Angelika; Kindler, Eveline; Gil-Cruz, Cristina; Ziebuhr, John; Thiel, Volker; Pichlmair, Andreas

2013-01-01

Viruses that generate capped RNA lacking 2′O methylation on the first ribose are severely affected by the antiviral activity of Type I interferons. We used proteome-wide affinity purification coupled to mass spectrometry to identify human and mouse proteins specifically binding to capped RNA with different methylation states. This analysis, complemented with functional validation experiments, revealed that IFIT1 is the sole interferon-induced protein displaying higher affinity for unmethylated than for methylated capped RNA. IFIT1 tethers a species-specific protein complex consisting of other IFITs to RNA. Pulsed stable isotope labelling with amino acids in cell culture coupled to mass spectrometry as well as in vitro competition assays indicate that IFIT1 sequesters 2′O-unmethylated capped RNA and thereby impairs binding of eukaryotic translation initiation factors to 2′O-unmethylated RNA template, which results in inhibition of translation. The specificity of IFIT1 for 2′O-unmethylated RNA serves as potent antiviral mechanism against viruses lacking 2′O-methyltransferase activity and at the same time allows unperturbed progression of the antiviral program in infected cells. PMID:24098121

Polar cap models of gamma-ray pulsars: Emision from single poles of nearly aligned rotators

NASA Technical Reports Server (NTRS)

Daugherty, Joseph K.; Harding, Alice K.

1994-01-01

We compare a new Monte Carlo simulation of polar cap models for gamma-ray pulsars with observations of sources detected above 10 MeV by the Compton Observatory (CGRO). We find that for models in which the inclination of the magnetic axis is comparable to the angular radius of the polar cap, the radiation from a single cap may exhibit a pusle with either a single broad peak as in PSR 1706-44 and PSR 1055-52, or a doubly peaked profile comparable to those observed from the Crab, Vela and Geminga pulsars. In general, double pulses are seen by observers whose line of sight penetrates into the cap interior and are due to enhanced emission near the rim. For cascades induced by culvature radiation, increased rim emission occurs even when electrons are accelerated over the entire cap, since electrons from the interior escape along magnetic field lines with less curvature and hence emit less radiation. However, we obtain better fits to the duty cycles of observed profiles if we make the empirical assumption that acceleration occurs only near the rim. In either case, the model energy spectra are consistent with most of the observed sources. The beaming factors expected from nearly aligned rotators, based on standard estimates for the cap radius, imply that their luminosities need not be as large as in the case of orthogonal rotators. However, small beam angles are also a difficutly with this model because they imply low detection probablities. In either case the polar cap radius is a critical factor, and in this context we point out that plasma loading of the field lines should make the caps larger than the usual estimates based on pure dipole fields.

Toward the mechanism of eIF4F-mediated ribosomal attachment to mammalian capped mRNAs.

PubMed

Kumar, Parimal; Hellen, Christopher U T; Pestova, Tatyana V

2016-07-01

Ribosomal attachment to mammalian capped mRNAs is achieved through the cap-eukaryotic initiation factor 4E (eIF4E)-eIF4G-eIF3-40S chain of interactions, but the mechanism by which mRNA enters the mRNA-binding channel of the 40S subunit remains unknown. To investigate this process, we recapitulated initiation on capped mRNAs in vitro using a reconstituted translation system. Formation of initiation complexes at 5'-terminal AUGs was stimulated by the eIF4E-cap interaction and followed "the first AUG" rule, indicating that it did not occur by backward scanning. Initiation complexes formed even at the very 5' end of mRNA, implying that Met-tRNAi (Met) inspects mRNA from the first nucleotide and that initiation does not have a "blind spot." In assembled initiation complexes, the cap was no longer associated with eIF4E. Omission of eIF4A or disruption of eIF4E-eIF4G-eIF3 interactions converted eIF4E into a specific inhibitor of initiation on capped mRNAs. Taken together, these results are consistent with the model in which eIF4E-eIF4G-eIF3-40S interactions place eIF4E at the leading edge of the 40S subunit, and mRNA is threaded into the mRNA-binding channel such that Met-tRNAi (Met) can inspect it from the first nucleotide. Before entering, eIF4E likely dissociates from the cap to overcome steric hindrance. We also found that the m(7)G cap specifically interacts with eIF3l. © 2016 Kumar et al.; Published by Cold Spring Harbor Laboratory Press.

7-methylguanosine diphosphate (m(7)GDP) is not hydrolyzed but strongly bound by decapping scavenger (DcpS) enzymes and potently inhibits their activity.

PubMed

Wypijewska, Anna; Bojarska, Elzbieta; Lukaszewicz, Maciej; Stepinski, Janusz; Jemielity, Jacek; Davis, Richard E; Darzynkiewicz, Edward

2012-10-09

Decapping scavenger (DcpS) enzymes catalyze the cleavage of a residual cap structure following 3' → 5' mRNA decay. Some previous studies suggested that both m(7)GpppG and m(7)GDP were substrates for DcpS hydrolysis. Herein, we show that mononucleoside diphosphates, m(7)GDP (7-methylguanosine diphosphate) and m(3)(2,2,7)GDP (2,2,7-trimethylguanosine diphosphate), resulting from mRNA decapping by the Dcp1/2 complex in the 5' → 3' mRNA decay, are not degraded by recombinant DcpS proteins (human, nematode, and yeast). Furthermore, whereas mononucleoside diphosphates (m(7)GDP and m(3)(2,2,7)GDP) are not hydrolyzed by DcpS, mononucleoside triphosphates (m(7)GTP and m(3)(2,2,7)GTP) are, demonstrating the importance of a triphosphate chain for DcpS hydrolytic activity. m(7)GTP and m(3)(2,2,7)GTP are cleaved at a slower rate than their corresponding dinucleotides (m(7)GpppG and m(3)(2,2,7)GpppG, respectively), indicating an involvement of the second nucleoside for efficient DcpS-mediated digestion. Although DcpS enzymes cannot hydrolyze m(7)GDP, they have a high binding affinity for m(7)GDP and m(7)GDP potently inhibits DcpS hydrolysis of m(7)GpppG, suggesting that m(7)GDP may function as an efficient DcpS inhibitor. Our data have important implications for the regulatory role of m(7)GDP in mRNA metabolic pathways due to its possible interactions with different cap-binding proteins, such as DcpS or eIF4E.

Cleft audit protocol for speech (CAPS-A): a comprehensive training package for speech analysis.

PubMed

Sell, D; John, A; Harding-Bell, A; Sweeney, T; Hegarty, F; Freeman, J

2009-01-01

The previous literature has largely focused on speech analysis systems and ignored process issues, such as the nature of adequate speech samples, data acquisition, recording and playback. Although there has been recognition of the need for training on tools used in speech analysis associated with cleft palate, little attention has been paid to this issue. To design, execute, and evaluate a training programme for speech and language therapists on the systematic and reliable use of the Cleft Audit Protocol for Speech-Augmented (CAPS-A), addressing issues of standardized speech samples, data acquisition, recording, playback, and listening guidelines. Thirty-six specialist speech and language therapists undertook the training programme over four days. This consisted of two days' training on the CAPS-A tool followed by a third day, making independent ratings and transcriptions on ten new cases which had been previously recorded during routine audit data collection. This task was repeated on day 4, a minimum of one month later. Ratings were made using the CAPS-A record form with the CAPS-A definition table. An analysis was made of the speech and language therapists' CAPS-A ratings at occasion 1 and occasion 2 and the intra- and inter-rater reliability calculated. Trained therapists showed consistency in individual judgements on specific sections of the tool. Intraclass correlation coefficients were calculated for each section with good agreement on eight of 13 sections. There were only fair levels of agreement on anterior oral cleft speech characteristics, non-cleft errors/immaturities and voice. This was explained, at least in part, by their low prevalence which affects the calculation of the intraclass correlation coefficient statistic. Speech and language therapists benefited from training on the CAPS-A, focusing on specific aspects of speech using definitions of parameters and scalar points, in order to apply the tool systematically and reliably. Ratings are enhanced by ensuring a high degree of attention to the nature of the data, standardizing the speech sample, data acquisition, the listening process together with the use of high-quality recording and playback equipment. In addition, a method is proposed for maintaining listening skills following training as part of an individual's continuing education.

In Situ Enzymatically Generated Photoswitchable Oxidase Mimetics and Their Application for Colorimetric Detection of Glucose Oxidase.

PubMed

Cao, Gen-Xia; Wu, Xiu-Ming; Dong, Yu-Ming; Li, Zai-Jun; Wang, Guang-Li

2016-07-09

In this study, a simple and amplified colorimetric assay is developed for the detection of the enzymatic activity of glucose oxidase (GOx) based on in situ formation of a photoswitchable oxidase mimetic of PO₄(3-)-capped CdS quantum dots (QDs). GOx catalyzes the oxidation of 1-thio-β-d-glucose to give 1-thio-β-d-gluconic acid which spontaneously hydrolyzes to β-d-gluconic acid and H₂S; the generated H₂S instantly reacts with Cd(2+) in the presence of Na₃PO₄ to give PO₄(3-)-stabilized CdS QDs in situ. Under visible-light (λ ≥ 400 nm) stimulation, the PO₄(3-)-capped CdS QDs are a new style of oxidase mimic derived by producing some active species, such as h⁺, (•)OH, O₂(•-) and a little H₂O₂, which can oxidize the typical substrate (3,3,5,5-tetramethylbenzydine (TMB)) with a color change. Based on the GOx-triggered growth of the oxidase mimetics of PO₄(3-)-capped CdS QDs in situ, we developed a simple and amplified colorimetric assay to probe the enzymatic activity of GOx. The proposed method allowed the detection of the enzymatic activity of GOx over the range from 25 μg/L to 50 mg/L with a low detection limit of 6.6 μg/L. We believe the PO₄(3-)-capped CdS QDs generated in situ with photo-stimulated enzyme-mimicking activity may find wide potential applications in biosensors.

Source parameter inversion of compound earthquakes on GPU/CPU hybrid platform

NASA Astrophysics Data System (ADS)

Wang, Y.; Ni, S.; Chen, W.

2012-12-01

Source parameter of earthquakes is essential problem in seismology. Accurate and timely determination of the earthquake parameters (such as moment, depth, strike, dip and rake of fault planes) is significant for both the rupture dynamics and ground motion prediction or simulation. And the rupture process study, especially for the moderate and large earthquakes, is essential as the more detailed kinematic study has became the routine work of seismologists. However, among these events, some events behave very specially and intrigue seismologists. These earthquakes usually consist of two similar size sub-events which occurred with very little time interval, such as mb4.5 Dec.9, 2003 in Virginia. The studying of these special events including the source parameter determination of each sub-events will be helpful to the understanding of earthquake dynamics. However, seismic signals of two distinctive sources are mixed up bringing in the difficulty of inversion. As to common events, the method(Cut and Paste) has been proven effective for resolving source parameters, which jointly use body wave and surface wave with independent time shift and weights. CAP could resolve fault orientation and focal depth using a grid search algorithm. Based on this method, we developed an algorithm(MUL_CAP) to simultaneously acquire parameters of two distinctive events. However, the simultaneous inversion of both sub-events make the computation very time consuming, so we develop a hybrid GPU and CPU version of CAP(HYBRID_CAP) to improve the computation efficiency. Thanks to advantages on multiple dimension storage and processing in GPU, we obtain excellent performance of the revised code on GPU-CPU combined architecture and the speedup factors can be as high as 40x-90x compared to classical cap on traditional CPU architecture.As the benchmark, we take the synthetics as observation and inverse the source parameters of two given sub-events and the inversion results are very consistent with the true parameters. For the events in Virginia, USA on 9 Dec, 2003, we re-invert source parameters and detailed analysis of regional waveform indicates that Virginia earthquake included two sub-events which are Mw4.05 and Mw4.25 at the same depth of 10km with focal mechanism of strike65/dip32/rake135, which are consistent with previous study. Moreover, compared to traditional two-source model method, MUL_CAP is more automatic with no need for human intervention.

Late-Onset Cryopyrin-Associated Periodic Syndromes Caused by Somatic NLRP3 Mosaicism-UK Single Center Experience.

PubMed

Rowczenio, Dorota M; Gomes, Sónia Melo; Aróstegui, Juan I; Mensa-Vilaro, Anna; Omoyinmi, Ebun; Trojer, Hadija; Baginska, Anna; Baroja-Mazo, Alberto; Pelegrin, Pablo; Savic, Sinisa; Lane, Thirusha; Williams, Rene; Brogan, Paul; Lachmann, Helen J; Hawkins, Philip N

2017-01-01

Cryopyrin-associated periodic syndrome (CAPS) is caused by gain-of-function NLRP3 mutations. Recently, somatic NLRP3 mosaicism has been reported in some CAPS patients who were previously classified as "mutation-negative." We describe here the clinical and laboratory findings in eight British adult patients who presented with symptoms typical of CAPS other than an onset in mid-late adulthood. All patients underwent comprehensive clinical and laboratory investigations, including analysis of the NLRP3 gene using Sanger and amplicon-based deep sequencing (ADS) along with measurements of extracellular apoptosis-associated speck-like protein with CARD domain (ASC) aggregates. The clinical phenotype in all subjects was consistent with mid-spectrum CAPS, except a median age at disease onset of 50 years. Sanger sequencing of NLRP3 was non-diagnostic but ADS detected a somatic NLRP3 mutation in each case. In one patient, DNA isolated from blood demonstrated an increase in the mutant allele from 5 to 45% over 12 years. ASC aggregates in patients' serum measured during active disease were significantly higher than healthy controls. This series represents 8% of CAPS patients diagnosed in a single center, suggesting that acquired NLRP3 mutations may not be an uncommon cause of the syndrome and should be sought in all patients with late-onset symptoms otherwise compatible with CAPS. Steadily worsening CAPS symptoms in one patient were associated with clonal expansion of the mutant allele predominantly affecting myeloid cells. Two patients developed AA amyloidosis, which previously has only been reported in CAPS in association with life-long germline NLRP3 mutations.

Child protective services utilization of child abuse pediatricians: A mixed methods study.

PubMed

Girardet, Rebecca; Bolton, Kelly; Hashmi, Syed; Sedlock, Emily; Khatri, Rachna; Lahoti, Nina; Lukefahr, James

2018-02-01

Several children's hospitals and medical schools across Texas have child abuse pediatricians (CAPs) who work closely with child protection workers to help ensure accurate assessments of the likelihood of maltreatment in cases of suspected abuse and neglect. Since the state does not mandate which cases should be referred to a CAP center, we were interested in studying factors that may influence workers' decisions to consult a CAP. We used a mixed methods study design consisting of a focus group followed by a survey. The focus group identified multiple factors that impact workers' decision-making, including several that involve medical providers. Responses from 436 completed surveys were compared to employees' number of years of employment and to the state region in which they worked. Focus group findings and survey responses revealed frustration among many workers when dealing with medical providers, and moderate levels of confidence in workers' abilities to make accurate determinations in cases involving medical information. Workers were more likely to refer cases involving serious physical injury than other types of cases. Among workers who reported prior interactions with a CAP, experiences and attitudes regarding CAPs were typically positive. The survey also revealed significant variability in referral practices by state region. Our results suggest that standard guidelines regarding CAP referrals may help workers who deal with cases involving medical information. Future research and quality improvement efforts to improve transfers of information and to better understand the qualities that CPS workers appreciate in CAP teams should improve CAP-CPS coordination. Copyright © 2017 Elsevier Ltd. All rights reserved.

Gossypol-Capped Mitoxantrone-Loaded Mesoporous SiO2 NPs for the Cooperative Controlled Release of Two Anti-Cancer Drugs.

PubMed

Heleg-Shabtai, Vered; Aizen, Ruth; Sharon, Etery; Sohn, Yang Sung; Trifonov, Alexander; Enkin, Natalie; Freage, Lina; Nechushtai, Rachel; Willner, Itamar

2016-06-15

Mesoporous SiO2 nanoparticles, MP-SiO2 NPs, are functionalized with the boronic acid ligand units. The pores of the MP-SiO2 NPs are loaded with the anticancer drug mitoxantrone, and the pores are capped with the anticancer drug gossypol. The resulting two-drug-functionalized MP-SiO2 NPs provide a potential stimuli-responsive anticancer drug carrier for cooperative chemotherapeutic treatment. In vitro experiments reveal that the MP-SiO2 NPs are unlocked under environmental conditions present in cancer cells, e.g., acidic pH and lactic acid overexpressed in cancer cells. The effective unlocking of the capping units under these conditions is attributed to the acidic hydrolysis of the boronate ester capping units and to the cooperative separation of the boronate ester bridges by the lactate ligand. The gossypol-capped mitoxantrone-loaded MP-SiO2 NPs reveals preferential cytotoxicity toward cancer cells and cooperative chemotherapeutic activities toward the cancer cells. The MCF-10A epithelial breast cells and the malignant MDA-MB-231 breast cancer cells treated with the gossypol-capped mitoxantrone-loaded MP-SiO2 NPs revealed after a time-interval of 5 days a cell death of ca. 8% and 60%, respectively. Also, the gossypol-capped mitoxantrone-loaded MP-SiO2 NPs revealed superior cancer-cell death (ca. 60%) as compared to control carriers consisting of β-cyclodextrin-capped mitoxantrone-loaded (ca. 40%) under similar loading of the mitoxantrone drug. The drugs-loaded MP-SiO2 NPs reveal impressive long-term stabilities.

Murine Efficacy and Pharmacokinetic Evaluation of the Flaviviral NS5 Capping Enzyme 2-Thioxothiazolidin-4-One Inhibitor BG-323

PubMed Central

Bullard, Kristen M.; Gullberg, Rebekah C.; Soltani, Elnaz; Steel, J. Jordan; Geiss, Brian J.; Keenan, Susan M.

2015-01-01

Arthropod-borne flavivirus infection continues to cause significant morbidity and mortality worldwide. Identification of drug targets and novel antiflaviviral compounds to treat these diseases has become a global health imperative. A previous screen of 235,456 commercially available small molecules identified the 2-thioxothiazolidin-4-one family of compounds as inhibitors of the flaviviral NS5 capping enzyme, a promising target for antiviral drug development. Rational drug design methodologies enabled identification of lead compound BG-323 from this series. We have shown previously that BG-323 potently inhibits NS5 capping enzyme activity, displays antiviral effects in dengue virus replicon assays and inhibits growth of West Nile and yellow fever viruses with low cytotoxicity in vitro. In this study we further characterized BG-323’s antiviral activity in vitro and in vivo. We found that BG-323 was able to reduce replication of WNV (NY99) and Powassan viruses in culture, and we were unable to force resistance into WNV (Kunjin) in long-term culture experiments. We then evaluated the antiviral activity of BG-323 in a murine model. Mice were challenged with WNV NY99 and administered BG-323 or mock by IP inoculation immediately post challenge and twice daily thereafter. Mice were bled and viremia was quantified on day three. No significant differences in viremia were observed between BG-323-treated and control groups and clinical scores indicated both BG-323-treated and control mice developed signs of illness on approximately the same day post challenge. To determine whether differences in in vitro and in vivo efficacy were due to unfavorable pharmacokinetic properties of BG-323, we conducted a pharmacokinetic evaluation of this small molecule. Insights from pharmacokinetic studies indicate that BG-323 is cell permeable, has a low efflux ratio and does not significantly inhibit two common cytochrome P450 (CYP P450) isoforms thus suggesting this molecule may be less likely to cause adverse drug interactions. However, the T1/2 of BG-323 was suboptimal and the percent of drug bound to plasma binding proteins was high. Future studies with BG-323 will be aimed at increasing the T1/2 and determining strategies for mitigating the effects of high plasma protein binding, which likely contribute to low in vivo efficacy. PMID:26075394

Murine Efficacy and Pharmacokinetic Evaluation of the Flaviviral NS5 Capping Enzyme 2-Thioxothiazolidin-4-One Inhibitor BG-323.

PubMed

Bullard, Kristen M; Gullberg, Rebekah C; Soltani, Elnaz; Steel, J Jordan; Geiss, Brian J; Keenan, Susan M

2015-01-01

Arthropod-borne flavivirus infection continues to cause significant morbidity and mortality worldwide. Identification of drug targets and novel antiflaviviral compounds to treat these diseases has become a global health imperative. A previous screen of 235,456 commercially available small molecules identified the 2-thioxothiazolidin-4-one family of compounds as inhibitors of the flaviviral NS5 capping enzyme, a promising target for antiviral drug development. Rational drug design methodologies enabled identification of lead compound BG-323 from this series. We have shown previously that BG-323 potently inhibits NS5 capping enzyme activity, displays antiviral effects in dengue virus replicon assays and inhibits growth of West Nile and yellow fever viruses with low cytotoxicity in vitro. In this study we further characterized BG-323's antiviral activity in vitro and in vivo. We found that BG-323 was able to reduce replication of WNV (NY99) and Powassan viruses in culture, and we were unable to force resistance into WNV (Kunjin) in long-term culture experiments. We then evaluated the antiviral activity of BG-323 in a murine model. Mice were challenged with WNV NY99 and administered BG-323 or mock by IP inoculation immediately post challenge and twice daily thereafter. Mice were bled and viremia was quantified on day three. No significant differences in viremia were observed between BG-323-treated and control groups and clinical scores indicated both BG-323-treated and control mice developed signs of illness on approximately the same day post challenge. To determine whether differences in in vitro and in vivo efficacy were due to unfavorable pharmacokinetic properties of BG-323, we conducted a pharmacokinetic evaluation of this small molecule. Insights from pharmacokinetic studies indicate that BG-323 is cell permeable, has a low efflux ratio and does not significantly inhibit two common cytochrome P450 (CYP P450) isoforms thus suggesting this molecule may be less likely to cause adverse drug interactions. However, the T1/2 of BG-323 was suboptimal and the percent of drug bound to plasma binding proteins was high. Future studies with BG-323 will be aimed at increasing the T1/2 and determining strategies for mitigating the effects of high plasma protein binding, which likely contribute to low in vivo efficacy.

Geological and geophysical properties of cap rock in a natural CO2 occurrence, Mihályi-Répcelak area, Western Hungary

NASA Astrophysics Data System (ADS)

Király, Csilla; Szamosfalvi, Ágnes; Sendula, Eszter; Páles, Mariann; Kovács, István; Kónya, Péter; Falus, György; Szabó, Csaba

2015-04-01

The physical and geochemical consistency of the cap rock is primarily important for safe geological storage of CO2.. As a consequence of CO2 injection reactions took place between the minerals of the reservoir, the cap rock and CO2 saturated pore water. These reactions may change the mineral composition and petrophysical properties of the storage reservoir as well as the cap rock that provides the only physical barrier that retains carbon dioxide in the target reservoir formation. Study of the natural CO2 occurrences delivers information to understand which properties of a cap rock provide the sustainable closure and retainment. Knowledge of the long term effect of CO2 on the behavior of the cap rock is an important input in the selection procedure of a potential CO2 injection site. Yet, very few data exist on geochemical properties and reactivity of the cap rocks. During normal commercial operations the reservoir is typically cored, but not the cap rock. This study may enhance our knowledge about possible mineralogical reactions, which can occur in clayey-aleuritic cap rocks. The Mihályi-Répcelak natural CO2 occurrence is believed to be leakage safe. There is no known seepage on the surface. It is suggested that the aleuritic clay rich cap rock occurring at the natural reservoir can stop CO2 migration into other reservoirs or to the surface. The most important characteristics of cap rocks that they have low permeability (<0.1 mD) and porosity (eff.por. = 4%) and high clayeyness (approx. 80%). However, we demonstrate that in addition to these parameters the geochemical properties of cap rock is also important. In order to characterize the natural CO2 occurrence, we applied the following analysis, like XRD, FTIR, SEM. The petrophysical properties are determined from the interpretation of geophysical well-logs and grain size distribution. The most important result of this study that adequate petrophysical properties do not completely define the suitability of a cap rock. The effective porosity (~4 %), permeability (0.026 mD) and clayeyness (~80%) data imply that the studied aleurolites are good cap rocks. The mineral composition of cap rock is similar to that of reservoir rock, however, the ratio of components is different. The mineralogical analysis and petrography yield to the reaction between CO2 and the cap rocks. The most visible effect of CO2 presence is the dawsonite precipitation after albite dissolution within the cap rocks. Therefore, the CO2 may migrate through the cap rocks in geological time scale, however the total system could be leakage safe.

Damage Tolerance Predictions for Spar Web Cracking in a Diminishing Stress Field

DTIC Science & Technology

2011-12-01

specimen crack. ....................... 40  28 NASGRO material file inputs for 7075 -T6 aluminum . .................................... 43  29 AFGROW...2024-T3511 aluminum end caps riveted to stiffened 7075 -T6 sheet metal aluminum webs. The cap-to-web attachment consisted of a double row of MS20470D8...section stress constant as the cracks 43 Fig. 28 NASGRO material file inputs for 7075 -T6 aluminum . grow. In this case, cracks are assumed to

Oxidative cyclizations in orthosomycin biosynthesis expand the known chemistry of an oxygenase superfamily

DOE PAGES

McCulloch, Kathryn M.; McCranie, Emilianne K.; Smith, Jarrod A.; ...

2015-08-03

Orthosomycins are oligosaccharide antibiotics that include avilamycin, everninomicin, and hygromycin B and are hallmarked by a rigidifying interglycosidic spirocyclic ortho-δ-lactone (orthoester) linkage between at least one pair of carbohydrates. A subset of orthosomycins additionally contain a carbohydrate capped by a methylenedioxy bridge. The orthoester linkage is necessary for antibiotic activity but rarely observed in natural products. Orthoester linkage and methylenedioxy bridge biosynthesis require similar oxidative cyclizations adjacent to a sugar ring. In this paper, we have identified a conserved group of nonheme iron, α-ketoglutarate–dependent oxygenases likely responsible for this chemistry. High-resolution crystal structures of the EvdO1 and EvdO2 oxygenases ofmore » everninomicin biosynthesis, the AviO1 oxygenase of avilamycin biosynthesis, and HygX of hygromycin B biosynthesis show how these enzymes accommodate large substrates, a challenge that requires a variation in metal coordination in HygX. Excitingly, the ternary complex of HygX with cosubstrate α-ketoglutarate and putative product hygromycin B identified an orientation of one glycosidic linkage of hygromycin B consistent with metal-catalyzed hydrogen atom abstraction from substrate. These structural results are complemented by gene disruption of the oxygenases evdO1 and evdMO1 from the everninomicin biosynthetic cluster, which demonstrate that functional oxygenase activity is critical for antibiotic production. Finally, our data therefore support a role for these enzymes in the production of key features of the orthosomycin antibiotics.« less

Selective induction of phospholipase D1 in pathogen-activated human monocytes.

PubMed

Locati, M; Riboldi, E; Bonecchi, R; Transidico, P; Bernasconi, S; Haribabu, B; Morris, A J; Mantovani, A; Sozzani, S

2001-08-15

Phospholipase D (PLD) activation is part of the complex signalling cascade induced during phagocyte activation. Two PLD isoforms have been cloned, but their role in phagocyte functions is still poorly defined. We report that resting fresh circulating human monocytes expressed PLD1. PLD1 protein expression was rapidly down-regulated during cell culture. Lipopolysaccharide and pathogen-derived agonists (Candida albicans, arabinoside-terminated lipoarabinomannan and Gram-positive bacteria, but not mannose-capped lipoarabinomannan or double-stranded RNA) strongly induced PLD1 expression at both the mRNA and protein levels. Pro-inflammatory cytokines [interleukin (IL)-1beta and tumour necrosis factor alpha] had only a weak effect, whereas immune cytokines (IL-6 and interferon gamma), anti-inflammatory cytokines (IL-13 and IL-10) and chemoattractants (fMet-Leu-Phe and macrophage chemoattractant protein 1) were inactive. None of the agonists tested induced significant changes in the basal expression of PLD2 mRNA. Consistent with PLD1 up-regulation was the observation that PLD enzymic activity was higher in monocytes treated with active-pathogen-derived agonists than in control cells, when stimulated with PMA or with chemotactic agonists (fMet-Leu-Phe and C5a). Thus PLD2 seems to be a constitutive enzyme in circulating monocytes. Conversely, PLD1 is an inducible protein, rapidly regulated during culture conditions and selectively induced during cell activation. Therefore PLD1 might have a relevant role in immune responses against pathogens and in chronic inflammation.

Closure Report for Corrective Action Unit 426: Cactus Spring Waste Trenches, Tonopah Test Range, Nevada

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

Dave Madsen

This Closure Report provides the documentation for closure of the Cactus Spring Waste Trenches Corrective Action Unit (CAU) 426. The site is located on the Tonopah Test Range, approximately 225 kilometers northwest of Las Vegas, NV. CAU 426 consists of one corrective action site (CAS) which is comprised of four waste trenches. The trenches were excavated to receive solid waste generated in support of Operation Roller Coaster, primary the Double Tracks Test in 1963, and were subsequently backfilled. The Double Tracks Test involved use of live animals to assess the biological hazards associated with the nonnuclear detonation of plutonium-bearing devices.more » The Nevada Division of Environmental Protection approved Corrective Action Plan (CAP)which proposed ''capping'' methodology. The closure activities were completed in accordance with the approved CAP and consisted of constructing an engineered cover in the area of the trenches, constructing/planting a vegetative cover, installing a perimeter fence and signs, implementing restrictions on future use, and preparing a Post-Closure Monitoring Plan.« less

[Usefulness of microbial investigations in community-acquired pneumonia].

PubMed

Putinati, S; Trevisani, L; Sighinolfi, L; Coletti, M; Battaglia, G; Potena, A

1992-03-01

Community acquired pneumonia (CAP) is a common and well known disease, however there is no definite agreement on a common diagnostic-therapeutic strategy. To evaluate the usefulness of microbial investigations in the clinical practice we performed a prospective study on 93 consecutive patients with a diagnosis of CAP. Group I consisted of 46 patients that underwent a diagnostic protocol including sputum, blood cultures and detection of specific antibodies against M. pneumoniae, adenovirus, respiratory syncytial virus, and L. pneumophila. Group II consisted of 47 patients, in which only sputum samples were collected and cultured. No significant differences concerning the aetiologic diagnosis, the outcome and the length of hospitalization were observed in the two groups. The aetiological diagnosis was obtained in 17 patients (18.3%). As result of information obtained from microbiol tests, antibiotic therapy was changed only in 6 patients. Among the prognostic factors only a low albumin level was correlated with the length of hospitalization (p less than 0.01). From our data, the detection of microbial aetiology should not be routinely performed in patients with CAP, but should be reserved only to the severe forms.

Interplanetary magnetic field dependency of stable Sun-aligned polar cap arcs

NASA Technical Reports Server (NTRS)

Valladares, C. E.; Carlson, H. C., Jr.; Fukui, K.

1994-01-01

This is the first analysis, using a statistically significant data set, of the morphological dependence of the presence, orientation, and motion of stable sun-aligned polar cap arcs upon the vector interplanetary magnetic field (IMF). For the one winter season analyzed we had 1392 all-sky 630.0-nm images of 2-min resolution containing a total of 150 polar cap arcs, all with corresponding values of the IMF as measured by International Monitoring Platform (IMP) 8 or International Sun Earth Explorer (ISEE) 2. After demonstrating an unbiased data set with smooth normal distributions of events versus the dimensions of time, space, and IMF component, we examine IMF dependencies of the properties of the optical arcs. A well-defined dependence for B(sub z) is found for the presence/absence of stable Sun-aligned polar cap arcs. Consistent with previous statistical studies, the probability of observing polar cap aurora steadily increases for larger positive values of B(sub z), and linearly decreases when B(sub z) becomes more negative. The probability of observing Sun-aligned arcs within the polar cap is determined to vary sharply as a function of the arc location; arcs were observed 40% of the time on the dawnside and only 10% on the duskside. This implies an overall probability of at least 40% for the whole polar cap. 20% of the arcs were observed during 'southward IMF conditions,' but in fact under closer inspection were found to have been formed under northward IMF conditions; these 'residual' positive B(sub z) arcs ha d a delayed residence time in the polar cap of about what would be expected after a north to south transition of B(sub z). A firm dependence on B(sub y) is also found for both the orientation and the dawn-dusk direction of motion of the arcs. All the arcs are Sun-aligned to a first approximation, but present deviations from this orientation, depending primarily upon the location of the arc in corrected geomagnetic (CG) coordinates. The arcs populating the 06-12 and the 12-18 quadrants of the CG coordinate system point toward the cusp. The B(sub y) dependency of the arc alignment is consistent with a cusp displacement in local time according to the sign of B(sub y). We found that the arc direction of motion depended both on B(sub y) and the arc location within the polar cap. For a given value of B(sub y) two well-defined regions (or cells) exist. Within each cell the arcs move in the same direction toward the boundary between the cells. The arcs located in the duskside move dawnward; those in the dawnside move duskward. The relative size of these dusk and dawn regions (or cells) are controlled by the magnitude of B(sub y). This persistent dusk-dawn motion fo the polar cap arcs is interpreted in terms of newly open flux tubes entering the polar cap and exerting a displacement of the convective cells and the polar cap arcs that are embedded within them.

A Panoptic Uncovering of the Dynamical Evolution of the Zika Virus NS5 Methyltransferase Binding Site Loops- Zeroing in on the Molecular Landscape.

PubMed

Devnarain, Nikita; Soliman, Mahmoud E S

2018-06-20

The global threat of the Zika virus to humanity is real. Innovative and potent anti-Zika virus drugs are still at large, due to the lack of anti-Zika virus drugs that have passed phase 1 trials. Experimental research has revealed novel inhibitors of Zika virus NS5 methyltransferase enzyme. This study has taken a step further to provide insight into the molecular dynamics of Zika virus and inhibitor binding, which have not been established experimentally. Movements of the methyltransferase binding site loops have a large role to play in the methylation of the viral mRNA cap, which is essential for Zika virus replication. Here we pinpoint the binding interactions between each potential inhibitor and the methyltransferase, residues that are responsible for binding, as well as which inhibitor-bound complex renders the methyltransferase more stable. We also highlight the conformational changes that occur within the methyltransferase to accommodate binding of inhibitors and consequences of those changes upon the RNA- and cap-binding sites in the methyltransferase. This research will improve the understanding of the Zika virus NS5 methyltransferase enzyme, and will be beneficial in driving the development of anti-Zika virus drugs. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The Conserved Foot Domain of RNA Pol II Associates with Proteins Involved in Transcriptional Initiation and/or Early Elongation

PubMed Central

García-López, M. Carmen; Pelechano, Vicent; Mirón-García, M. Carmen; Garrido-Godino, Ana I.; García, Alicia; Calvo, Olga; Werner, Michel; Pérez-Ortín, José E.; Navarro, Francisco

2011-01-01

RNA polymerase (pol) II establishes many protein–protein interactions with transcriptional regulators to coordinate different steps of transcription. Although some of these interactions have been well described, little is known about the existence of RNA pol II regions involved in contact with transcriptional regulators. We hypothesize that conserved regions on the surface of RNA pol II contact transcriptional regulators. We identified such an RNA pol II conserved region that includes the majority of the “foot” domain and identified interactions of this region with Mvp1, a protein required for sorting proteins to the vacuole, and Spo14, a phospholipase D. Deletion of MVP1 and SPO14 affects the transcription of their target genes and increases phosphorylation of Ser5 in the carboxy-terminal domain (CTD). Genetic, phenotypic, and functional analyses point to a role for these proteins in transcriptional initiation and/or early elongation, consistent with their genetic interactions with CEG1, a guanylyltransferase subunit of the Saccharomyces cerevisiae capping enzyme. PMID:21954159

Frequency of respiratory viruses among patients admitted to 26 Intensive Care Units in seven consecutive winter-spring seasons (2009-2016) in Northern Italy.

PubMed

Piralla, Antonio; Mariani, Bianca; Rovida, Francesca; Baldanti, Fausto

2017-07-01

The role of respiratory viruses in the etiology of community-acquired pneumonia (CAP) is still debated. The advent of molecular assays has improved the identification of viruses in patients with CAP and according to published studies, viruses account for 11-55% of adult CAP cases. In the present study, the frequency of respiratory viruses was evaluated in respiratory samples collected from 414 patients with CAP admitted to 26 ICUs in the Lombardy Region (10 million inhabitants) during seven winter-spring seasons (2009-2016). In 226 (54.6%) patients one or more respiratory viruses were identified, while 188 (45.4%) patients were negative. A single virus infection was observed in 214/226 (94.7%) patients; while, in 12/226 (5.3%) at least two respiratory viruses were detected. Influenza A was the most common virus in 140/226 patients (61.9%) followed by rhinoviruses (33/226, 14.6%), respiratory syncytial virus (13/226, 5.8%), influenza B virus (9/226, 4.0%), human coronaviruses (9/226, 4.0%), cytomegalovirus (9/226, 4.0%) and human metapneumovirus (1/226, 0.4%). Viral infections are present in a consistent proportion of patients admitted to the ICU for CAP. Influenza A and rhinovirus accounted for three-quarters of all CAP in ICU patients. The use of lower respiratory instead of upper respiratory samples might be useful in the diagnosis of viral CAP. Copyright © 2017 Elsevier B.V. All rights reserved.

Child and adolescent psychiatry in the Far East.

PubMed

Hirota, Tomoya; Guerrero, Anthony; Sartorius, Norman; Fung, Daniel; Leventhal, Bennett; Ong, Say How; Kaneko, Hitoshi; Kim, Bungnyun; Cho, Soo-Churl; Skokauskas, Norbert

2015-03-01

Despite the general consensus on the importance of youth mental health, the scarcity of child and adolescent mental health services is prominent all over the world. Child and adolescent psychiatry (CAP) postgraduate training can play a pivotal role in increasing access to youth mental health services. In comparison to Europe and North America, however, little is reported regarding CAP training in the Far East, one of the most dynamic and rapidly developing world regions with a very young population. This paper presents an original study on the current status of academic child and adolescent psychiatry training across the Far East. We collected data from 17 countries in the Far East using an internally distributed questionnaire to the Consortium members invited for this study, consisting of leading academic child and adolescent psychiatrists in each country. Based on informants' input, we found an overall underdevelopment of CAP postgraduate training systems despite CAP's recognition as a subspecialty in 12 of 17 of the nations or functionally self-governing areas in the Far East. Paucity of official guidelines for CAP training was also evident. All informants reported a need for additional child and adolescent mental health professionals. There seems to be several obstacles to the development of CAP postgraduate training in the Far East, including stigma towards mental health issues and lack of funding. International collaboration is desired to develop evidence-based and culture-tailored CAP training systems. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

Effect of Organic Capping Layers over Monodisperse Platinum Nanoparticles upon Activity for Ethylene Hydrogenation and Carbon Monoxide Oxidation

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

Kuhn, John N.; Tsung, Chia-Kuang; Huang, Wenyu

2009-03-24

The influence of oleylamine (OA), trimethyl tetradecyl ammonium bromide (TTAB), and polyvinlypyrrolidone (PVP) capping agents upon the catalytic properties of Pt/silica catalysts was evaluated. Pt nanoparticles that were 1.5 nm in size were synthesized by the same procedure (ethylene glycol reduction under basic conditions) with the various capping agents added afterward for stabilization. Before examining catalytic properties for ethylene hydrogenation and CO oxidation, the Pt NPs were deposited onto mesoporous silica (SBA-15) supports and characterized by transmission electron microscopy (TEM), H{sub 2} chemisorption, and elemental analysis (ICP-MS). PVP- and TTAB-capped Pt yielded mass-normalized reaction rates that decreased with increasing pretreatmentmore » temperature, and this trend was attributed to the partial coverage of the Pt surface with decomposition products from the organic capping agent. Once normalized to the Pt surface area, similar intrinsic activities were obtained regardless of the pretreatment temperature, which indicated no influence on the nature of the active sites. Consequently, a chemical probe technique using intrinsic activity for ethylene hydrogenation was demonstrated as an acceptable method for estimating the metallic surface areas of Pt. Amine (OA) capping exhibited a detrimental influence on the catalytic properties as severe deactivation and low activity were observed for ethylene hydrogenation and CO oxidation, respectively. These results were consistent with amine groups being strong poisons for Pt surfaces, and revealed the need to consider the effects of capping agents on the catalytic properties.« less

Effects of prosodically-modulated sub-phonetic variation on lexical competition

PubMed Central

Salverda, Anne Pier; Dahan, Delphine; Tanenhaus, Michael K.; Crosswhite, Katherine; Masharov, Mikhail; McDonough, Joyce

2007-01-01

Eye movements were monitored as participants followed spoken instructions to manipulate one of four objects pictured on a computer screen. Target words occurred in utterance-medial (e.g., Put the cap next to the square) or utterance-final position (e.g., Now click on the cap). Displays consisted of the target picture (e.g., a cap), a monosyllabic competitor picture (e.g., a cat), a polysyllabic competitor picture (e.g., a captain) and a distractor (e.g., a beaker). The relative proportion of fixations to the two types of competitor pictures changed as a function of the position of the target word in the utterance, demonstrating that lexical competition is modulated by prosodically-conditioned phonetic variation. PMID:17141751

Thiolate-Capped CdSe/ZnS Core-Shell Quantum Dots for the Sensitive Detection of Glucose.

PubMed

Abd Rahman, Samsulida; Ariffin, Nurhayati; Yusof, Nor Azah; Abdullah, Jaafar; Mohammad, Faruq; Ahmad Zubir, Zuhana; Nik Abd Aziz, Nik Mohd Azmi

2017-07-01

A semiconducting water-soluble core-shell quantum dots (QDs) system capped with thiolated ligand was used in this study for the sensitive detection of glucose in aqueous samples. The QDs selected are of CdSe-coated ZnS and were prepared in house based on a hot injection technique. The formation of ZnS shell at the outer surface of CdSe core was made via a specific process namely, SILAR (successive ionic layer adsorption and reaction). The distribution, morphology, and optical characteristics of the prepared core-shell QDs were assessed by transmission electron microscopy (TEM) and spectrofluorescence, respectively. From the analysis, the results show that the mean particle size of prepared QDs is in the range of 10-12 nm and that the optimum emission condition was displayed at 620 nm. Further, the prepared CdSe/ZnS core shell QDs were modified by means of a room temperature ligand-exchange method that involves six organic ligands, L -cysteine, L -histidine, thio-glycolic acid (TGA or mercapto-acetic acid, MAA), mercapto-propionic acid (MPA), mercapto-succinic acid (MSA), and mercapto-undecanoic acid (MUA). This process was chosen in order to maintain a very dense water solubilizing environment around the QDs surface. From the analysis, the results show that the CdSe/ZnS capped with TGA (CdSe/ZnS-TGA) exhibited the strongest fluorescence emission as compared to others; hence, it was tested further for the glucose detection after their treatment with glucose oxidase (GOx) and horseradish peroxidase (HRP) enzymes. Here in this study, the glucose detection is based on the fluorescence quenching effect of the QDs, which is correlated to the oxidative reactions occurred between the conjugated enzymes and glucose. From the analysis of results, it can be inferred that the resultant GOx:HRP/CdSe/ZnS-TGA QDs system can be a suitable platform for the fluorescence-based determination of glucose in the real samples.

Direct Regulation of Androgen Receptor Activity by Potent CYP17 Inhibitors in Prostate Cancer Cells*

PubMed Central

Soifer, Harris S.; Souleimanian, Naira; Wu, Sijian; Voskresenskiy, Anatoliy M.; Kisaayak Collak, Filiz; Cinar, Bekir; Stein, Cy A.

2012-01-01

TOK-001 and abiraterone are potent 17-heteroarylsteroid (17-HAS) inhibitors of Cyp17, one of the rate-limiting enzymes in the biosynthesis of testosterone from cholesterol in prostate cancer cells. Nevertheless, the molecular mechanism underlying the prevention of prostate cell growth by 17-HASs still remains elusive. Here, we assess the effects of 17-HASs on androgen receptor (AR) activity in LNCaP and LAPC-4 cells. We demonstrate that both TOK-001 and abiraterone reduced AR protein and mRNA expression, and antagonized AR-dependent promoter activation induced by androgen. TOK-001, but not abiraterone, is an effective apparent competitor of the radioligand [3H]R1881 for binding to the wild type and various mutant AR (W741C, W741L) proteins. In agreement with these data, TOK-001 is a consistently superior inhibitor than abiraterone of R1881-induced transcriptional activity of both wild type and mutant AR. However, neither agent was able to trans-activate the AR in the absence of R1881. Our data demonstrate that phospho-4EBP1 levels are significantly reduced by TOK-001 and to a lesser extent by abiraterone alcohol, and suggest a mechanism by which cap-dependent translation is suppressed by blocking assembly of the eIF4F and eIF4G complex to the mRNA 5′ cap. Thus, the effects of these 17-HASs on AR signaling are complex, ranging from a decrease in testosterone production through the inhibition of Cyp17 as previously described, to directly reducing both AR protein expression and R1881-induced AR trans-activation. PMID:22174412

3 Benzyl-6-chloropyrone: a suicide inhibitor of cholesterol esterase

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

Saint, C.; Gallo, I.; Kantorow, M.

Cholesterol, absorbed from the intestine, appears in lymph as the ester. Cholesterol esterase is essential for this process, since depletion of the enzyme blocks and repletion restores, absorption. Selective inhibitors of cholesterol esterase may thus prove useful in reducing cholesterol uptake. A series of potential suicide substrates were synthesized which, following cleavage by the enzyme, would attack the putative nucleophile in the active site. One of these, 3-benzyl-6-chloropyrone (3BCP), inhibited both synthesis and hydrolysis of /sup 14/C-cholesteryl oleate with an I/sub 50/ of approximately 150 ..mu..M. The inactivation was time-dependent and characteristic of a suicide mechanism. The ..cap alpha.. pyronemore » structure (lactone analog) is cleaved by a serine-hydroxyl in the active site. This generates an enoyl chloride which inactivates the imidazole believed to play a part in the catalytic function of the enzyme. Inhibition by 3BCP is selective for cholesterol esterase. The activity of pancreatic lipase as not affected by concentrations up to 1 mM.« less

Response of Buried Vertically Oriented Cylinders to Dynamic Loading,

DTIC Science & Technology

1980-06-01

BALSARA • , . / ,, _,-, -. 1i S ,LESPONSE OF BURIED VERTICALLY 9RIENTED CYLINDERS 𔃺 .-TO DINAMIC LOADING_ 9AYLE E. LRTOrwW&-N JIIMY P./BALSARA Nk...1.7, 2,8, and 4.0 inches). The end caps for the cylinders consisted of a steel shell filled with high- strength concrete; however, the end caps were...not designed to be test articles. The average concrete compressive strength of the cylinders on test day was 44.0 MPa (6,380 psi). The three DEOT

Acoustic field of a wedge-shaped section of a spherical cap transducer

NASA Astrophysics Data System (ADS)

Ketterling, Jeffrey A.

2003-12-01

The acoustic pressure field at an arbitrary point in space is derived for a wedge-shaped section of a spherical cap transducer using the spatial impulse response (SIR) method. For a spherical surface centered at the origin, a wedge shape is created by taking cuts in the X-Y and X-Z planes and removing the smallest surface component. Analytic expressions are derived for the SIR based on spatial location. The expressions utilize the SIR solutions for a spherical cap transducer [Arditi et al., Ultrason. Imaging 3, 37-61 (1981)] with additional terms added to account for the reduced surface area of the wedge. Results from the numerical model are compared to experimental measurements from a wedge transducer with an 8-cm outer diameter and 9-cm geometric focus. The experimental and theoretical -3-dB beamwidths agreed to within 10%+/-5%. The SIR model for a wedge-shaped transducer is easily extended to other spherically curved transducer geometries that consist of combinations of wedge sections and spherical caps.

Acoustic field of a wedge-shaped section of a spherical cap transducer.

PubMed

Ketterling, Jeffrey A

2003-12-01

The acoustic pressure field at an arbitrary point in space is derived for a wedge-shaped section of a spherical cap transducer using the spatial impulse response (SIR) method. For a spherical surface centered at the origin, a wedge shape is created by taking cuts in the X-Y and X-Z planes and removing the smallest surface component. Analytic expressions are derived for the SIR based on spatial location. The expressions utilize the SIR solutions for a spherical cap transducer [Arditi et al., Ultrason. Imaging 3, 37-61 (1981)] with additional terms added to account for the reduced surface area of the wedge. Results from the numerical model are compared to experimental measurements from a wedge transducer with an 8-cm outer diameter and 9-cm geometric focus. The experimental and theoretical -3-dB beamwidths agreed to within 10% +/- 5%. The SIR model for a wedge-shaped transducer is easily extended to other spherically curved transducer geometries that consist of combinations of wedge sections and spherical caps.

Incidence of the concrete scalp deformity associated with deep scalp donor sites and management with the Unna cap.

PubMed

Carter, Y M; Summer, G J; Engrav, L H; Hansen, F L; Costa, B A; Matsumura, H

1999-01-01

The scalp has become a popular donor site for split-thickness skin grafts. This donor site does, however, have complications, including the concrete scalp deformity, which consists of hairs embedded in a thick, desiccated, exudative crust. This article presents our burn unit's experience with this complication. Fifty-six patients underwent scalp skin graft harvesting between 1984 and 1996. All grafts were quite thick and were used for resurfacing facial burns. Thirty-eight donor sites were treated with medicated gauze, and 18 were treated with the Unna cap, which is an Unna dressing applied over Aquaphor gauze (Beiersdorf, Norwalk, Conn). Eighteen of the 38 patients (32%) treated with medicated gauze developed the concrete scalp deformity. None of the patients treated with the Unna cap developed the deformity. Although useful, the deep scalp donor site has complications, including the concrete scalp deformity. However, with use of the Unna cap dressing, we have had no occurrences of this problem.

Paths to future growth in photovoltaics manufacturing

DOE PAGES

Basore, Paul A.

2016-03-01

The past decade has seen rapid growth in the photovoltaics industry, followed in the past few years by a period of much slower growth. A simple model that is consistent with this historical record can be used to predict the future evolution of the industry. Two key parameters are identified that determine the outcome. One is the annual global investment in manufacturing capacity normalized to the manufacturing capacity for the previous year (capacity-normalized capital investment rate, CapIR, units dollar/W). The other is how much capital investment is required for each watt of annual manufacturing capacity, normalized to the service lifemore » of the assets (capacity-normalized capital demand rate, CapDR, units dollar/W). If these two parameters remain unchanged from the values they have held for the past few years, global manufacturing capacity will peak in the next few years and then decline. However, it only takes a modest improvement in CapIR to ensure future growth in photovoltaics. Here, several approaches are presented that can enable the required improvement in CapIR. If, in addition, there is an accompanying improvement in CapDR, the rate of growth can be substantially accelerated.« less

Mapping the functional roles of cap cells in the response of Arabidopsis primary roots to gravity

NASA Technical Reports Server (NTRS)

Blancaflor, E. B.; Fasano, J. M.; Gilroy, S.; Evans, M. L. (Principal Investigator)

1998-01-01

The cap is widely accepted to be the site of gravity sensing in roots because removal of the cap abolishes root curvature. Circumstantial evidence favors the columella cells as the gravisensory cells because amyloplasts (and often other cellular components) are polarized with respect to the gravity vector. However, there has been no functional confirmation of their role. To address this problem, we used laser ablation to remove defined cells in the cap of Arabidopsis primary roots and quantified the response of the roots to gravity using three parameters: time course of curvature, presentation time, and deviation from vertical growth. Ablation of the peripheral cap cells and tip cells did not alter root curvature. Ablation of the innermost columella cells caused the strongest inhibitory effect on root curvature without affecting growth rates. Many of these roots deviated significantly from vertical growth and had a presentation time 6-fold longer than the controls. Among the two inner columella stories, the central cells of story 2 contributed the most to root gravitropism. These cells also exhibited the largest amyloplast sedimentation velocities. Therefore, these results are consistent with the starch-statolith sedimentation hypothesis for gravity sensing.

Changing Criminal Attitudes Among Incarcerated Offenders: Initial Examination of a Structured Treatment Program.

PubMed

Simourd, David J; Olver, Mark E; Brandenburg, Bryan

2016-09-01

The present study investigated the effect of a criminal attitude treatment program to changes on measured criminal attitudes and postprogram recidivism. The criminal attitude program (CAP) is a standardized therapeutic curriculum consisting of 15 modules offering 44 hr of therapeutic time. It was delivered by trained facilitators to a total of 113 male offenders incarcerated in one of five state correctional institutions. Pretreatment and posttreatment comparisons were made on standardized measures of criminal attitudes, response bias, and motivation for lifestyle changes. Results found statistically significant lower criminal attitudes at posttreatment that were unaffected by response bias. There were also increases in motivation for lifestyle changes, but these did not reach statistical significance. Fifty-seven participants were released into the community following the program and were eligible for recidivism analyses. Comparisons between participants who completed the CAP and those who did not complete the CAP revealed 7% lower rearrest among CAP completers. Although preliminary, these results indicate that the CAP had a positive effect on changes to criminal attitudes and recidivism. The findings are discussed in terms of conceptual and practical considerations in the assessment and treatment of criminal attitudes among offenders. © The Author(s) 2015.

Association between Work-Family Conflict and Depressive Symptoms among Chinese Female Nurses: The Mediating and Moderating Role of Psychological Capital.

PubMed

Hao, Junhui; Wu, Di; Liu, Li; Li, Xirui; Wu, Hui

2015-06-12

Depressive symptoms have been in the limelight for many kinds of people, but few studies have explored positive resources for combating depressive symptoms among Chinese nurses. The purpose of this study is to explore the association between work-family conflict (WFC) and depressive symptoms among Chinese female nurses, along with the mediating and moderating role of psychological capital (PsyCap) in this relationship. This cross-sectional study was completed during the period of September and October 2013. A questionnaire that consisted of the Center for Epidemiologic Studies Depression Scale, the Work-Family Conflict scale and the Psychological Capital Questionnair scale was distributed to nurses in Shenyang, China. A total of 824 individuals (effective response rate: 74.9%) participated. Asymptotic and resampling strategies explored the mediating role of PsyCap in the relationship between WFC and depressive symptoms. Hierarchical linear regression analyses were performed to explore the moderating role of PsyCap. Both WFC and family-work conflict (FWC) were positively related with depressive symptoms. PsyCap positively moderated the relationship of WFC with depressive symptoms. Self-efficacy and hope positively moderated the relationship of WFC with depressive symptoms. PsyCap partially mediated the relationship of FWC with depressive symptoms. Hope and optimism partially mediated the relationship of FWC with depressive symptoms. Work-family conflict, as the risk factor of depressive symptoms, can increase nurses' depressive symptoms, and PsyCap is a positive resource to combat nurses' depressive symptoms. PsyCap can aggravate the effects of WFC on depressive symptoms and FWC can impact PsyCap to increase nurses' depressive symptoms.

Late-Onset Cryopyrin-Associated Periodic Syndromes Caused by Somatic NLRP3 Mosaicism—UK Single Center Experience

PubMed Central

Rowczenio, Dorota M.; Gomes, Sónia Melo; Aróstegui, Juan I.; Mensa-Vilaro, Anna; Omoyinmi, Ebun; Trojer, Hadija; Baginska, Anna; Baroja-Mazo, Alberto; Pelegrin, Pablo; Savic, Sinisa; Lane, Thirusha; Williams, Rene; Brogan, Paul; Lachmann, Helen J.; Hawkins, Philip N.

2017-01-01

Cryopyrin-associated periodic syndrome (CAPS) is caused by gain-of-function NLRP3 mutations. Recently, somatic NLRP3 mosaicism has been reported in some CAPS patients who were previously classified as “mutation-negative.” We describe here the clinical and laboratory findings in eight British adult patients who presented with symptoms typical of CAPS other than an onset in mid-late adulthood. All patients underwent comprehensive clinical and laboratory investigations, including analysis of the NLRP3 gene using Sanger and amplicon-based deep sequencing (ADS) along with measurements of extracellular apoptosis-associated speck-like protein with CARD domain (ASC) aggregates. The clinical phenotype in all subjects was consistent with mid-spectrum CAPS, except a median age at disease onset of 50 years. Sanger sequencing of NLRP3 was non-diagnostic but ADS detected a somatic NLRP3 mutation in each case. In one patient, DNA isolated from blood demonstrated an increase in the mutant allele from 5 to 45% over 12 years. ASC aggregates in patients’ serum measured during active disease were significantly higher than healthy controls. This series represents 8% of CAPS patients diagnosed in a single center, suggesting that acquired NLRP3 mutations may not be an uncommon cause of the syndrome and should be sought in all patients with late-onset symptoms otherwise compatible with CAPS. Steadily worsening CAPS symptoms in one patient were associated with clonal expansion of the mutant allele predominantly affecting myeloid cells. Two patients developed AA amyloidosis, which previously has only been reported in CAPS in association with life-long germline NLRP3 mutations. PMID:29163488

Association between Work-Family Conflict and Depressive Symptoms among Chinese Female Nurses: The Mediating and Moderating Role of Psychological Capital

PubMed Central

Hao, Junhui; Wu, Di; Liu, Li; Li, Xirui; Wu, Hui

2015-01-01

Depressive symptoms have been in the limelight for many kinds of people, but few studies have explored positive resources for combating depressive symptoms among Chinese nurses. The purpose of this study is to explore the association between work-family conflict (WFC) and depressive symptoms among Chinese female nurses, along with the mediating and moderating role of psychological capital (PsyCap) in this relationship. This cross-sectional study was completed during the period of September and October 2013. A questionnaire that consisted of the Center for Epidemiologic Studies Depression Scale, the Work-Family Conflict scale and the Psychological Capital Questionnair scale was distributed to nurses in Shenyang, China. A total of 824 individuals (effective response rate: 74.9%) participated. Asymptotic and resampling strategies explored the mediating role of PsyCap in the relationship between WFC and depressive symptoms. Hierarchical linear regression analyses were performed to explore the moderating role of PsyCap. Both WFC and family-work conflict (FWC) were positively related with depressive symptoms. PsyCap positively moderated the relationship of WFC with depressive symptoms. Self-efficacy and hope positively moderated the relationship of WFC with depressive symptoms. PsyCap partially mediated the relationship of FWC with depressive symptoms. Hope and optimism partially mediated the relationship of FWC with depressive symptoms. Work-family conflict, as the risk factor of depressive symptoms, can increase nurses’ depressive symptoms, and PsyCap is a positive resource to combat nurses’ depressive symptoms. PsyCap can aggravate the effects of WFC on depressive symptoms and FWC can impact PsyCap to increase nurses’ depressive symptoms. PMID:26075725

Metabolic fate of lactoferricin-based antimicrobial peptides: effect of truncation and incorporation of amino acid analogs on the in vitro metabolic stability.

PubMed

Svenson, Johan; Vergote, Valentijn; Karstad, Rasmus; Burvenich, Christian; Svendsen, John S; De Spiegeleer, Bart

2010-03-01

A series of promising truncated antibacterial tripeptides derived from lactoferricin has been prepared, and their in vitro metabolic stability in the main metabolic compartments, plasma, liver, kidney, stomach, duodenum, and brain, has been investigated for the first time. The potential stabilizing effect of truncation, C-terminal capping, and introduction of the bulky synthetic amino acid biphenylalanine is also investigated. The drug-like peptides displayed large differences in half-lives in the different matrixes ranging from 4.2 min in stomach and duodenum to 355.9 min in liver. Kinetic analysis of the metabolites revealed that several different degrading enzymes simultaneously target the different peptide bonds and that the outcome of the tested strategies to increase the stability is clearly enzyme-specific. Some of the metabolic enzymes even prefer the synthetic modifications incorporated over the natural counterparts. Collectively, it is shown that the necessary antibacterial pharmacophore generates compounds that are not only potent antibacterial peptides, but excellent substrates for the main degrading enzymes. All the amide bonds are thus rapidly targeted by different enzymes despite the short peptidic sequences of the tested compounds. Hence, our results illustrate that several structural changes are needed before these compounds can be considered for oral administration. Strategies to overcome such metabolic challenges are discussed.

California air transportation study: A transportation system for the California Corridor of the year 2010

NASA Technical Reports Server (NTRS)

1989-01-01

To define and solve the problems of transportation in the California Corrider in the year 2010, the 1989 California Polytechnic State University Aeronautical Engineering Senior Design class determined future corridor transportation needs and developed a system to meet the requirements. A market study, which included interpreting travel demand and gauging the future of regional and national air travel in and out of the corridor, allowed the goals of the project to be accurately refined. Comprehensive trade-off studies of several proposed transporation systems were conducted to determine which components would form the final proposed system. Preliminary design and further analysis were performed for each resulting component. The proposed system consists of three vehicles and a special hub or mode mixer, the Corridor Access Port (CAP). The vehicles are: (1) an electric powered aircraft to serve secondary airports and the CAP; (2) a high speed magnetic levitation train running through the CAP and the high population density areas of the corridor; and (3) a vertical takeoff and landing tilt rotor aircraft to serve both intercity and intrametropolitan travelers from the CAP and city vertiports. The CAP is a combination and an extension of the hub, mode mixer, and Wayport concepts. The CAP is an integrated part of the system which meets the travel demands in the corridor, and interfaces with interstate and international travel.

Etiologic spectrum and occurrence of coinfections in children hospitalized with community-acquired pneumonia.

PubMed

Jiang, Wujun; Wu, Min; Zhou, Jing; Wang, Yuqing; Hao, Chuangli; Ji, Wei; Zhang, Xinxing; Gu, Wenjing; Shao, Xuejun

2017-12-20

Co-infections are common in childhood community acquired pneumonia (CAP). However, their etiological pattern and clinical impact remains inconclusive. Eight hundred forty-six consecutive children with CAP were evaluated prospectively for the presence of viral and bacterial pathogens. Nasopharyngeal aspirates were examined by direct immunofluorescence assay or polymerase chain reaction (PCR) for viruses. PCR of nasopharyngeal aspirates and enzyme-linked immunosorbent assays were performed to detect M. pneumoniae. Bacteria was detected in blood, bronchoalveolar lavage specimen, or pleural fluid by culture. Causative pathogen was identified in 70.1% (593 of 846) of the patients. The most commonly detected pathogens were respiratory syncytial virus (RSV) (22.9%), human rhinovirus (HRV) (22.1%), M. pneumoniae (15.8%). Coinfection was identified in 34.6% (293 of 846) of the patients. The majority of these (209 [71.3%] of 293) were mixed viral-bacterial infections. Age < 6 months (odds ratio: 2.1; 95% confidence interval: 1.2-3.3) and admission of PICU (odds ratio: 12.5; 95% confidence interval: 1.6-97.4) were associated with mix infection. Patients with mix infection had a higher rate of PICU admission. The high mix infection burden in childhood CAP underscores a need for the enhancement of sensitive, inexpensive, and rapid diagnostics to accurately identify pneumonia pathogens.

The Ca2+-induced methyltransferase xPRMT1b controls neural fate in amphibian embryo.

PubMed

Batut, Julie; Vandel, Laurence; Leclerc, Catherine; Daguzan, Christiane; Moreau, Marc; Néant, Isabelle

2005-10-18

We have previously shown that an increase in intracellular Ca2+ is both necessary and sufficient to commit ectoderm to a neural fate in Xenopus embryos. However, the relationship between this Ca2+ increase and the expression of early neural genes has yet to be defined. Using a subtractive cDNA library between untreated and caffeine-treated animal caps, i.e., control ectoderm and ectoderm induced toward a neural fate by a release of Ca2+, we have isolated the arginine N-methyltransferase, xPRMT1b, a Ca2+-induced target gene, which plays a pivotal role in this process. First, we show in embryo and in animal cap that xPRMT1b expression is Ca2+-regulated. Second, overexpression of xPRMT1b induces the expression of early neural genes such as Zic3. Finally, in the whole embryo, antisense approach with morpholino oligonucleotide against xPRMT1b impairs neural development and in animal caps blocks the expression of neural markers induced by a release of internal Ca2+. Our results implicate an instructive role of an enzyme, an arginine methyltransferase protein, in the embryonic choice of determination between epidermal and neural fate. The results presented provide insights by which a Ca2+ increase induces neural fate.

Treatment with Entinostat Heals Experimental Cholera by Affecting Physical and Chemical Barrier Functions of Intestinal Epithelia.

PubMed

Sarker, Protim; Banik, Atanu; Stromberg, Roger; Gudmundsson, Gudmundur H; Raqib, Rubhana; Agerberth, Birgitta

2017-07-01

We have shown previously that oral treatment with sodium butyrate or phenylbutyrate in an experimental model of shigellosis improves clinical outcomes and induces the expression of the antimicrobial peptide CAP-18 in the large intestinal epithelia. In a subsequent study, we found that entinostat, an aroylated phenylenediamine compound, has similar therapeutic potential against shigellosis. In this study, we aimed to evaluate entinostat as a potential candidate for host-directed therapy against cholera in an experimental model. Vibrio cholerae -infected rabbits were treated with two different dose regimens of entinostat: either 0.5 mg twice daily for 2 days or 1 mg once daily for 2 days. The effects of treatment on clinical outcomes and V. cholerae shedding (CFU count in stool) were observed. Immunohistochemical analysis was carried out to assess CAP-18 expression in ileal and jejunal mucosae. The serum zonulin level was measured by an enzyme-linked immunosorbent assay (ELISA) to evaluate gut permeability. Infection of rabbits with V. cholerae downregulated CAP-18 expression in the ileal epithelium; the expression was replenished by oral treatment with entinostat at either dose regimen. The level of zonulin, a marker of gut permeability, in serum was upregulated after infection, and this upregulation was counteracted after treatment with entinostat. Entinostat treatment also led to recovery from cholera and a decline in the V. cholerae count in stool. In conclusion, the improved clinical outcome of cholera for rabbits treated with entinostat is associated with the induction of CAP-18 and the reduction of gut epithelial permeability. Copyright © 2017 American Society for Microbiology.

Synthesis and characterization of nanosized calcium phosphates by flame spray pyrolysis, and their effect on osteogenic differentiation of stem cells

NASA Astrophysics Data System (ADS)

Ataol, Sibel; Tezcaner, Ayşen; Duygulu, Ozgur; Keskin, Dilek; Machin, Nesrin E.

2015-02-01

The present study evaluates the synthesis of biocompatible osteoconductive and osteoinductive nano calcium phosphate (CaP) particles by industrially applied, aerosol-derived flame spray pyrolysis method for biomedical field. Calcium phosphate nanoparticles were produced in a range of calcium-to-phosphorus ratio, (1.20-2.19) in order to analyze the morphology and crystallinity changes, and to test the bioactivity of particles. The characterization results confirmed that nanometer-sized, spherical calcium phosphate particles were produced. The average primary particle size was determined as 23 nm by counting more than 500 particles in TEM pictures. XRD patterns, HRTEM, SAED, and SEM analyses revealed the amorphous nature of the as-prepared nano calcium phosphate particles at low Ca/P ratios. Increases in the specific surface area and crystallinity were observed with the increasing Ca/P ratio. TGA-DTA analysis showed that the thermally stable crystal phases formed after 700 °C. Cell culture studies were conducted with urine-derived stem cells that possess the characteristics of mesenchymal stem cells. Synthesized amorphous nanoparticles did not have cytotoxic effect at 5-50 μg/ml concentration range. Cells treated with the as-prepared nanoparticles had higher alkaline phosphatase (ALP) enzyme activity than control cells, indicating osteogenic differentiation of cells. A slight decrease in ALP activity of cells treated with two highest Ca:P ratios at 50 μg/ml concentration was observed at day 7. The findings suggest that calcium phosphate nanoparticles produced in this work have a potential to be used as biomaterials in biomedical applications.

Child welfare professionals' determination of when children's access or potential access to loaded firearms constitutes child neglect.

PubMed

Evans, Erin M; Jennissen, Charles A; Oral, Resmiye; Denning, Gerene M

2017-11-01

Pediatric deaths and injuries from access to firearms are a significant public health problem. No studies have examined how experts determine child neglect regarding firearm access in the home. Our study objectives were to identify factors that influenced pediatric experts' finding of firearm-related child neglect and to assess their attitudes toward child access prevention (CAP) laws. A survey was distributed to the American Academy of Pediatrics Section on Child Abuse and Neglect members. Demographics, attitudes regarding CAP laws, and ages (up to 14 years old) at which experts deemed several scenarios as child neglect were determined. Scenarios tested potential versus actual loaded firearm access, presence or absence of a CAP law, and injury versus no injury when the firearm was accessed. One hundred ninety-three surveys were completed. Experts agreed (>95%) that CAP laws were important, even for children up to age 15 years. Although a high percentage considered potential access to a loaded firearm as child neglect, a CAP law significantly increased the percentage for each age. In addition, higher percentages of respondents from states with CAP laws than those without deemed potential access as child neglect for 12- and 14-year-olds. In contrast, if the child had accessed a loaded firearm, there were no significant differences in the high percentages that deemed the scenario as child neglect under any conditions, including with and without a CAP law. Although almost all child neglect experts considered potential and actual access to loaded firearms as child neglect, CAP laws increased the percentage for cases of potential access. Universal CAP laws may help ensure that determinations of child neglect are more consistent across states. The deterrent effect of potential child neglect findings may increase the number of parents securing firearms in ways that prevent child access and reduce firearm-related deaths and injuries. Epidemiologic study, level III.

Improved noninvasive prediction of liver fibrosis by liver stiffness measurement in patients with nonalcoholic fatty liver disease accounting for controlled attenuation parameter values.

PubMed

Petta, Salvatore; Wong, Vincent Wai-Sun; Cammà, Calogero; Hiriart, Jean-Baptiste; Wong, Grace Lai-Hung; Marra, Fabio; Vergniol, Julien; Chan, Anthony Wing-Hung; Di Marco, Vito; Merrouche, Wassil; Chan, Henry Lik-Yuen; Barbara, Marco; Le-Bail, Brigitte; Arena, Umberto; Craxì, Antonio; de Ledinghen, Victor

2017-04-01

Liver stiffness measurement (LSM) frequently overestimates the severity of liver fibrosis in nonalcoholic fatty liver disease (NAFLD). Controlled attenuation parameter (CAP) is a new parameter provided by the same machine used for LSM and associated with both steatosis and body mass index, the two factors mostly affecting LSM performance in NAFLD. We aimed to determine whether prediction of liver fibrosis by LSM in NAFLD patients is affected by CAP values. Patients (n = 324) were assessed by clinical and histological (Kleiner score) features. LSM and CAP were performed using the M probe. CAP values were grouped by tertiles (lower 132-298, middle 299-338, higher 339-400 dB/m). Among patients with F0-F2 fibrosis, mean LSM values, expressed in kilopascals, increased according to CAP tertiles (6.8 versus 8.6 versus 9.4, P = 0.001), and along this line the area under the curve of LSM for the diagnosis of F3-F4 fibrosis was progressively reduced from lower to middle and further to higher CAP tertiles (0.915, 0.848-0.982; 0.830, 0.753-0.908; 0.806, 0.723-0.890). As a consequence, in subjects with F0-F2 fibrosis, the rates of false-positive LSM results for F3-F4 fibrosis increased according to CAP tertiles (7.2% in lower versus 16.6% in middle versus 18.1% in higher). Consistent with this, a decisional flowchart for predicting fibrosis was suggested by combining both LSM and CAP values. In patients with NAFLD, CAP values should always be taken into account in order to avoid overestimations of liver fibrosis assessed by transient elastography. (Hepatology 2017;65:1145-1155). © 2016 by the American Association for the Study of Liver Diseases.

Hybrid calcium phosphate coatings for implants

NASA Astrophysics Data System (ADS)

Malchikhina, Alena I.; Shesterikov, Evgeny V.; Bolbasov, Evgeny N.; Ignatov, Viktor P.; Tverdokhlebov, Sergei I.

2016-08-01

Monophasic biomaterials cannot provide all the necessary functions of bones or other calcined tissues. It is necessary to create for cancer patients the multiphase materials with the structure and composition simulating the natural bone. Such materials are classified as hybrid, obtained by a combination of chemically different components. The paper presents the physical, chemical and biological studies of coatings produced by hybrid technologies (HT), which combine primer layer and calcium phosphate (CaP) coating. The first HT type combines the method of vacuum arc titanium primer layer deposition on a stainless steel substrate with the following micro-arc oxidation (MAO) in phosphoric acid solution with addition of calcium compounds to achieve high supersaturated state. MAO CaP coatings feature high porosity (2-8%, pore size 5-7 µm) and surface morphology with the thickness greater than 5 µm. The thickness of Ti primer layer is 5-40 µm. Amorphous MAO CaP coating micro-hardness was measured at maximum normal load Fmax = 300 mN. It was 3.1 ± 0.8 GPa, surface layer elasticity modulus E = 110 ± 20 GPa, roughness Ra = 0.9 ± 0.1 µm, Rz = 7.5 ± 0.2 µm, which is less than the titanium primer layer roughness. Hybrid MAO CaP coating is biocompatible, able to form calcium phosphates from supersaturated body fluid (SBF) solution and also stimulates osteoinduction processes. The second HT type includes the oxide layer formation by thermal oxidation and then CaP target radio frequency magnetron sputtering (RFMS). Oxide-RFMS CaP coating is a thin dense coating with good adhesion to the substrate material, which can be used for metal implants. The RFMS CaP coating has thickness 1.6 ± 0.1 µm and consists of main target elements calcium and phosphorus and Ca/P ratio 2.4. The second HT type can form calcium phosphates from SBF solution. In vivo study shows that hybrid RFMS CaP coating is biocompatible and produces fibrointegration processes.

Rocket measurements within a polar cap arc - Plasma, particle, and electric circuit parameters

NASA Technical Reports Server (NTRS)

Weber, E. J.; Ballenthin, J. O.; Basu, S.; Carlson, H. C.; Hardy, D. A.; Maynard, N. C.; Kelley, M. C.; Fleischman, J. R.; Pfaff, R. F.

1989-01-01

Results are presented from the Polar Ionospheric Irregularities Experiment (PIIE), conducted from Sondrestrom, Greenland, on March 15, 1985, designed for an investigation of processes which lead to the generation of small-scale (less than 1 km) ionospheric irregularities within polar-cap F-layer auroras. An instrumented rocket was launched into a polar cap F layer aurora to measure energetic electron flux, plasma, and electric circuit parameters of a sun-aligned arc, coordinated with simultaneous measurements from the Sondrestrom incoherent scatter radar and the AFGL Airborne Ionospheric Observatory. Results indicated the existence of two different generation mechanisms on the dawnside and duskside of the arc. On the duskside, parameters are suggestive of an interchange process, while on the dawnside, fluctuation parameters are consistent with a velocity shear instability.

Chromosomal aberrations and delays in cell progression induced by x-rays in Tradescantia clone 02 meristems

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

Geard, C.R.

1983-01-01

In root meristems of Tradescantia clone 02 (developed by Sparrow and his colleagues for mutation studies), X-rays interfere with the progression of cells through the cell cycle and induce chromosomal aberrations in a dose-dependent manner consistent with linear-quadratic kinetics. Sequential mitotic cell accumulations after irradiation indicate that sensitivity to aberration induction is probably greatest in cells from late S to early G2, with chromatid interchanges the most frequent aberration type and all aberrations consistent with initiation from the interaction between two lesions. The ratio of the coefficients in the linear (..cap alpha..) and the quadratic (..beta..) terms (..cap alpha../..beta..) ismore » equal to the dose average of specific energy produced by individual particles in the site where interaction takes place. The ratio ..cap alpha../..beta.. for chromosomal aberrations is similar to that previously found for X-ray-induced mutation in Tradescantia stamen hairs, supporting the proposal that radiation-induced mutational events are due to chromosomal aberrations with interaction distances of about 1..mu..m. Abrahamson and co-workers have noted that both ..cap alpha../..beta.. ratios appear to be related to nuclear target size and are similar for chromosomal and mutational endpoints in the same organism. These findings support this concept; however, it is apparent that any situation which diminishes yield at high doses (e.g., mitotic delay) will probably affect the ..beta.. component. 23 references, 5 figures, 2 tables.« less

Chromosomal aberrations and delays in cell progression induced by x-rays in Tradescantia clone 02 meristems

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

Geard, C.R.

1983-01-01

In root meristems of Tradescantia clone 02 (developed by Sparrow and his colleagues for mutation studies), X-rays interfere with the progression of cells through the cell cycle and induce chromosomal aberrations in a dose-dependent manner consistent with linear-quadratic kinetics. Sequential mitotic cell accumulations after irradiation indicate that sensitivity to aberrration induction is probably greatest in cells from late S to early G2, with chromatid interchanges the most frequent aberration type and all aberrations consistent with intiation from the interaction between two lesions. The ratio of the coefficients in the linear (..cap alpha..) and the quadratic (..beta..) terms (..cap alpha../..beta..) ismore » equal to the dose average of specific energy produced by individual particles in the site where interaction takes place. The ratio ..cap alpha../..beta.. for chromosomal aberrations is similar to that previously found for X-ray-induced mutation in Tradescantia stamen hairs, supporting the proposal that radiation-induced mutational events are due to chromosomal aberrations with interaction distances of about 1 ..mu..m. Abrahmson and co-workers have noted that both ..cap alpha../..beta.. ratios appear to be related to nuclear target size and are similar for chromosomal and mutational endpoints in the same organism. These findings support this concept; however, it is apparent that any situation which diminishes yield at high doses (e.g., mitotic delay) will primarily affect the ..beta.. component, resulting in low assessments of interaction site diameters.« less

Does the family cap influence birthrates? Two new studies say "no".

PubMed

Donovan, P

1998-02-01

Some have argued that imposing a cap upon welfare benefits would reduce birthrates among welfare recipients. However, recent studies in New Jersey and Arkansas determined that denying an increase in cash assistance to women who have another child while on welfare has no effect upon births in the states. When New Jersey became the first state, 4 years ago, to impose a family cap, then-governor James Florio declared the cap a success after just 2 months. An analysis by researchers at Rutgers University released in September 1997 disagrees. While birthrates among welfare recipients declined between August 1992 and July 1995, the decline was no different from that observed in a control group which continued to receive a benefit increase if they had another child. Among both groups, and consistent with birthrates in the general New Jersey population, birthrates fell from 11% in 1992-93 to 6% in 1994-95. These results did not change when researchers controlled for the age and race of the almost 8500 women studied. Abortion rates in the state declined both among women subject to the cap and among the control group. Although researchers studying the impact of the family cap in Arkansas could not determine its effect upon abortion rates because Arkansas fails to pay for abortions under Medicaid, no statistically significant difference was observed between the birthrates of women subject to the cap and a control group. The findings of these 2 studies cast doubt upon the notion that an increase in monthly benefits after the birth of a new baby is an incentive for welfare recipients to have more children.

Martian North Polar Water-Ice Clouds During the Viking Era

NASA Technical Reports Server (NTRS)

Tamppari, L. K.; Bass, D. S.

2000-01-01

The Viking Orbiters determined that the surface of Mars' northern residual cap consists of water ice. Observed atmospheric water vapor abundances in the equatorial regions have been related to seasonal exchange between reservoirs such as the polar caps, the regolith and between different phases in the atmosphere. Kahn modeled the physical characteristics of ice hazes seen in Viking Orbiter imaging limb data, hypothesizing that ice hazes provide a method for scavenging water vapor from the atmosphere and accumulating it into ice particles. Given that Jakosky found that these particles had sizes such that fallout times were of order one Martian sol, these water-ice hazes provided a method for returning more water to the regolith than that provided by adsorption alone. These hazes could also explain the rapid hemispheric decrease in atmospheric water in late northern summer as well as the increase during the following early spring. A similar comparison of water vapor abundance versus polar cap brightness has been done for the north polar region. They have shown that water vapor decreases steadily between L(sub s) = 100-150 deg while polar cap albedo increases during the same time frame. As a result, they suggested that late summer water-ice deposition onto the ice cap may be the cause of the cap brightening. This deposition could be due to adsorption directly onto the cap surface or to snowfall. Thus, an examination of north polar waterice clouds could lend insight into the fate of the water vapor during this time period. Additional information is contained in the original extended abstract.

Pressure compensated flow control valve

DOEpatents

Minteer, Daniel J.

1999-01-01

The invention is an air flow control valve which is capable of maintaining a constant flow at the outlet despite changes in the inlet or outlet pressure. The device consists of a shell assembly with an inlet chamber and outlet chamber separated by a separation plate. The chambers are connected by an orifice. Also located within the inlet chamber is a port controller assembly. The port controller assembly consists of a differential pressure plate and port cap affixed thereon. The cap is able to slide in and out of the orifice separating the inlet and outlet chambers. When the pressure differential is sufficient, the differential pressure plate rises or falls to maintain a constant air flow. Movement of the port controller assembly does not require the use of seals, diaphragms, tight tolerances, bushings, bearings, hinges, guides, or lubricants.

Hypoglycemic and Hypolipidemic Effects of the Cracked-Cap Medicinal Mushroom Phellinus rimosus (Higher Basidiomycetes) in Streptozotocin-Induced Diabetic Rats.

PubMed

Rony, Kuttikkadan A; Ajith, Thekkuttuparambil A; Janardhanan, Kainoor K

2015-01-01

Phellinus rimosus is a parasitic host specific polypore mushroom with profound antioxidant, antihepatotoxic, anti-inflammatory, antitumor, and antimutagenic activities. This study investigated the hypoglycemic and hypolipidemic activities of the wood-inhabiting polypore mushroom Ph. Rimosus in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by single intraperitoneal injection of STZ (45 mg/kg) to Wistar rats. The effects of 30 days treatment with Ph. Rimosus (50 and 250 mg/ kg) and glibenclamide (0.65 mg/kg) on blood glucose level, serum insulin, serum lipid profile, liver glycogen, liver function enzymes, and non-enzymic and enzymic antioxidants activities in pancreas, liver, and kidney were evaluated in STZ-induced diabetic rats. Oral administration of Ph. Rimosus extract exhibited a significant reduction in blood glucose, triacylglycerol, total cholesterol, LDL-cholesterol, and liver function enzymes, and increased serum insulin, liver glycogen, and HDL-cholesterol levels in STZ-induced diabetic rats. Furthermore, Ph. Rimosus treatment increased antioxidant status in pancreas, liver, and kidney tissues with concomitant decreases in levels of thiobarbituric acid- reactive substances. Results of this study indicated that Ph. Rimosus possessed significant hypoglycemic and hypolipidemic activities and this effect may be related to its insulinogenic and antioxidant effect.

Standardized system for quantifying residual dirt on medical appliances cleansed in hospital washers--disinfectors: dirt detection by different methods.

PubMed

Sigler, K; Gásková, D; Chládková, K; Knebl, R; Wimmer, T; Vacata, V; Gebel, J

2003-01-01

An easy-to construct, easy-to-operate standardized system was developed for determining the residual biological contamination of surgical instruments, endoscopes and other medical appliances subjected to hospital cleansing and/or disinfection. It consists of standard-sized pieces of glass, metal or endoscope plastic--dirt carriers--either bare or enclosed in truncated Eppendorf caps to simulate hard-to-access conditions. The surface of the carriers is covered with model dirt simulating biological contamination and the carriers are then affixed to sturdy metal holders. Conventional model dirt were found to peel or flake off the carrier surface, lowering the precision of residual soil determination. A newly developed model dirt consisting of liver mash, lactose and sunflower oil and exhibiting low tendency to peel off surfaces was therefore used. The whole setup was subjected to chemical or enzymic cleansing programs at elevated temperature in hospital washer-disinfectors of two types, and the residual dirt after cleansing was determined by three methods. The method using toxicant-doped dirt that quenches the luminescence of an indicator bacterium Photobacterium phosphoreum gave satisfactory data under laboratory conditions but with hospital-washed samples it exhibited excessive fluctuations caused by bacterium--dirt interactions and by physical influences. Both other methods gave better results but displayed some process sensitivity. The luciferin-luciferase-based ATP bioluminescence assay sometimes gave low or even negative dirt level values and showed a low effect of reduced dirt accessibility on cleansing of metal carriers. The Bradford protein assay showed about equal cleansing efficiency for both easily and poorly accessible carriers after enzymic cleansing. Our system can be used for determining low levels of residual contamination of medical appliances after cleansing/disinfection and assessing the efficiency of commercial washer-disinfectors; its efficiency can be further increased by using a cleansing process-insensitive method for soil detection and quantification.

Identification of small molecule inhibitors of the Chikungunya virus nsP1 RNA capping enzyme.

PubMed

Feibelman, Kristen M; Fuller, Benjamin P; Li, Linfeng; LaBarbera, Daniel V; Geiss, Brian J

2018-06-01

Chikungunya virus (CHIKV) is an arthropod-borne alphavirus. Alphaviruses are positive strand RNA viruses that require a 5' cap structure to direct translation of the viral polyprotein and prevent degradation of the viral RNA genome by host cell nucleases. Formation of the 5' RNA cap is orchestrated by the viral protein nsP1, which binds GTP and provides the N-7 methyltransferase and guanylyltransferase activities that are necessary for cap formation. Viruses with aberrant nsP1 activity are unable to replicate effectively suggesting that nsP1 is a promising target for antiviral drug discovery. Given the absence of commercially available antiviral therapies for CHIKV, it is imperative to identify compounds that could be developed as potential therapeutics. This study details a high-throughput screen of 3051 compounds from libraries containing FDA-approved drugs, natural products, and known bioactives against CHIKV nsP1 using a fluorescence polarization-based GTP competition assay. Several small molecule hits from this screen were able to compete with GTP for the CHIKV nsP1 GTP binding site at low molar concentrations. Compounds were also evaluated with an orthogonal assay that measured the ability of nsP1 to perform the guanylation step of the capping reaction in the presence of inhibitor. In addition, live virus assays with CHIKV and closely related alphavirus, Sindbis virus, were used in conjunction with cell toxicity assays to determine the antiviral activity of compounds in cell culture. The naturally derived compound lobaric acid was found to inhibit CHIKV nsP1 GTP binding and guanylation as well as attenuate viral growth in vitro at both 24 hpi and 48 hpi in hamster BHK21 and human Huh 7 cell lines. These data indicate that development of lobaric acid and further exploration of CHIKV nsP1 as a drug target may aid in the progress of anti-alphaviral drug development strategies. Copyright © 2018. Published by Elsevier B.V.

VISIONS: Remote Observations of a Spatially-Structured Filamentary Source of Energetic Neutral Atoms near the Polar Cap Boundary During an Auroral Substorm

NASA Technical Reports Server (NTRS)

Collier, Michael R.; Chornay, D.; Clemmons, J.; Keller, J. W.; Klenzing, J.; Kujawski, J.; McLain, J.; Pfaff, R.; Rowland, D.; Zettergren, M.

2015-01-01

We report initial results from the VISualizing Ion Outflow via Neutral atom imaging during a Substorm (VISIONS) rocket that flew through and near several regions of enhanced auroral activity and also sensed regions of ion outflow both remotely and directly. The observed neutral atom fluxes were largest at the lower energies and generally higher in the auroral zone than in the polar cap. In this paper, we focus on data from the latter half of the VISIONS trajectory when the rocket traversed the polar cap region. During this period, many of the energetic neutral atom spectra show a peak at 100 electronvolts. Spectra with peaks around 100 electronvolts are also observed in the Electrostatic Ion Analyzer (EIA) data consistent with these ions comprising the source population for the energetic neutral atoms. The EIA observations of this low energy population extend only over a few tens of kilometers. Furthermore, the directionality of the arriving energetic neutral atoms is consistent with either this spatially localized source of energetic ions extending from as low as about 300 kilometers up to above 600 kilometers or a larger source of energetic ions to the southwest.

The German version of the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5): psychometric properties and diagnostic utility.

PubMed

Krüger-Gottschalk, Antje; Knaevelsrud, Christine; Rau, Heinrich; Dyer, Anne; Schäfer, Ingo; Schellong, Julia; Ehring, Thomas

2017-11-28

The Posttraumatic Stress Disorder (PTSD) Checklist (PCL, now PCL-5) has recently been revised to reflect the new diagnostic criteria of the disorder. A clinical sample of trauma-exposed individuals (N = 352) was assessed with the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) and the PCL-5. Internal consistencies and test-retest reliability were computed. To investigate diagnostic accuracy, we calculated receiver operating curves. Confirmatory factor analyses (CFA) were performed to analyze the structural validity. Results showed high internal consistency (α = .95), high test-retest reliability (r = .91) and a high correlation with the total severity score of the CAPS-5, r = .77. In addition, the recommended cutoff of 33 on the PCL-5 showed high diagnostic accuracy when compared to the diagnosis established by the CAPS-5. CFAs comparing the DSM-5 model with alternative models (the three-factor solution, the dysphoria, anhedonia, externalizing behavior and hybrid model) to account for the structural validity of the PCL-5 remained inconclusive. Overall, the findings show that the German PCL-5 is a reliable instrument with good diagnostic accuracy. However, more research evaluating the underlying factor structure is needed.

Characterization of vitamin D insensitive prostate cancer cells

PubMed Central

Alagbala, Adebusola A.; Johnson, Candace S.; Trump, Donald L.; Foster, Barbara A.

2007-01-01

The antitumor effects of 1,25-dihydroxyvitamin D3 (calcitriol) are being exploited for prevention and treatment of prostate cancer (CaP). These studies examined antitumor effects of calcitriol in primary cell cultures derived from transgenic adenocarcinoma of mouse prostate (TRAMP) mice chronically treated with calcitriol (20μg/kg) or vehicle 3x/week (MWF) from 4 weeks-of-age until palpable tumors developed. This is a report on the response of 2 representative control (vitamin D naïve, naïve) and calcitriol-treated (vitamin D insensitive, VDI) cells to calcitriol. VDI cells were less sensitive to calcitriol based on less cell growth inhibition and less inhibition of DNA synthesis as measured by MTT and BrdU incorporation assays. Similarly, VDI cells were also less sensitive to growth inhibition by the vitamin analog, 19-nor-1α,25-dihydroxyvitamin D2 (paricalcitol). There was no change in apoptosis following treatment of naïve and VDI cells with calcitriol. Vitamin D receptor (VDR) expression was up-regulated by calcitriol in both naïve and VDI cells. Calcitriol induced the vitamin D metabolizing enzyme, 24-hydroxylase (cyp24) mRNA and enzyme activity similarly in naïve and VDI cells as measured by RT-PCR and HPLC respectively. In summary, VDI cells are less responsive to the antiproliferative effects of calcitriol. Understanding vitamin D insensitivity will further clinical development of vitamin D compounds for prevention and treatment of CaP. PMID:17280828

Possible recent and ancient glacial ice flow in the south polar region of Mars

NASA Technical Reports Server (NTRS)

Kargel, J. S.

1992-01-01

Martian polar science began almost as soon as small telescopes were trained on the planet. The seasonal expansion and contraction of the polar caps and their high albedoes led most astronomers to think that water ice is the dominant constituent. In 1911 Lowell perceived a bluish band around the retreating edge of the polar caps, and interpreted it as water from melting polar ice and seasonal snow. An alternative idea in his time was that the polar caps consist of frozen carbonic acid. Lowell rejected the carbonic acid hypothesis on account of his blue band. He also pointed out that carbonic acid would sublimate rather than melt at confining pressures near and below one bar, hence, carbonic acid could not account for the blue band. In comparing Lowell's theories with today's knowledge, it is recognized that (1) sublimation is mainly responsible for the growth and contraction of Mars' polar caps, (2) carbon dioxide is a major component of the southern polar cap, and (3) Lowell's blue band was probably seasonal dust and/or clouds. Geomorphic evidence that glacial ice and glacial melt waters once flowed over broad areas of the southern polar region. Two aspects of the south polar region suggest possible glacial processes during two distinct eras in Mars' history.

A Chronology of Late-Glacial and Holocene Advances of Quelccaya Ice Cap, Peru, Based on 10Be and Radiocarbon Dating

NASA Astrophysics Data System (ADS)

Kelly, M. A.; Lowell, T. V.; Schaefer, J. M.

2007-12-01

The Quelccaya Ice Cap region in the southeastern Peruvian Andes (~13-14°S latitude) is a key location for the development of late-glacial and Holocene terrestrial paleoclimate records in the tropics. We present a chronology of past extents of Quelccaya Ice Cap based on ~thirty internally consistent 10Be dates of boulders on moraines and bedrock as well as twenty radiocarbon dates of organic material associated with moraines. Based on results from both dating methods, we suggest that significant advances of Quelccaya Ice Cap occurred during late-glacial time, at ~12,700-11,400 yr BP, and during Late Holocene time ~400-300 yr BP. Radiocarbon dating of organic material associated with moraines provides maximum and minimum ages for ice advances and recessions, respectively, thus providing an independent check on 10Be dates of boulders on moraines. The opportunity to use both 10Be and radiocarbon dating makes the Quelccaya Ice Cap region a potentially important low-latitude calibration site for production rates of cosmogenic nuclides. Our radiocarbon chronology provides a tighter constraint on maximum ages of late-glacial and Late Holocene ice advances. Upcoming field research will obtain organic material for radiocarbon dating to improve minimum age constrains for late-glacial and Late Holocene ice recessions.

Synthesis, Surface Modification and Optical Properties of Thioglycolic Acid-Capped ZnS Quantum Dots for Starch Recognition at Ultralow Concentration

NASA Astrophysics Data System (ADS)

Tayebi, Mahnoush; Tavakkoli Yaraki, Mohammad; Ahmadieh, Mahnaz; Mogharei, Azadeh; Tahriri, Mohammadreza; Vashaee, Daryoosh; Tayebi, Lobat

2016-11-01

In this research, water-soluble thioglycolic acid-capped ZnS quantum dots (QDs) are synthesized by the chemical precipitation method. The prepared QDs are characterized using x-ray diffraction and transmission electron microscopy. Results revealed that ZnS QDs have a 2.73 nm crystallite size, cubic zinc blende structure, and spherical morphology with a diameter less than 10 nm. Photoluminescence (PL) spectroscopy is performed to determine the presence of low concentrations of starch. Four emission peaks are observed at 348 nm, 387 nm, 422 nm, and 486 nm and their intensities are quenched by increasing concentration of starch. PL intensity variations in the studied concentrations range (0-100 ppm) are best described by a Michaelis-Menten model. The Michaelis constant ( K m) for immobilized α-amylase in this system is about 101.07 ppm. This implies a great tendency for the enzyme to hydrolyze the starch as substrate. Finally, the limit of detection is found to be about 6.64 ppm.

Self-Assembly of Telechelic Tyrosine End-Capped PEO Star Polymers in Aqueous Solution.

PubMed

Edwards-Gayle, Charlotte J C; Greco, Francesca; Hamley, Ian W; Rambo, Robert P; Reza, Mehedi; Ruokolainen, Janne; Skoulas, Dimitrios; Iatrou, Hermis

2018-01-08

We investigate the self-assembly of two telechelic star polymer-peptide conjugates based on poly(ethylene oxide) (PEO) four-arm star polymers capped with oligotyrosine. The conjugates were prepared via N-carboxy anhydride-mediated ring-opening polymerization from PEO star polymer macroinitiators. Self-assembly occurs above a critical aggregation concentration determined via fluorescence probe assays. Peptide conformation was examined using circular dichroism spectroscopy. The structure of self-assembled aggregates was probed using small-angle X-ray scattering and cryogenic transmission electron microscopy. In contrast to previous studies on linear telechelic PEO-oligotyrosine conjugates that show self-assembly into β-sheet fibrils, the star architecture suppresses fibril formation and micelles are generally observed instead, a small population of fibrils only being observed upon pH adjustment. Hydrogelation is also suppressed by the polymer star architecture. These peptide-functionalized star polymer solutions are cytocompatible at sufficiently low concentration. These systems present tyrosine at high density and may be useful in the development of future enzyme or pH-responsive biomaterials.

Insights into RNA synthesis, capping, and proofreading mechanisms of SARS-coronavirus.

PubMed

Sevajol, Marion; Subissi, Lorenzo; Decroly, Etienne; Canard, Bruno; Imbert, Isabelle

2014-12-19

The successive emergence of highly pathogenic coronaviruses (CoVs) such as the Severe Acute Respiratory Syndrome (SARS-CoV) in 2003 and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in 2012 has stimulated a number of studies on the molecular biology. This research has provided significant new insight into functions and activities of the replication/transcription multi-protein complex. The latter directs both continuous and discontinuous RNA synthesis to replicate and transcribe the large coronavirus genome made of a single-stranded, positive-sense RNA of ∼30 kb. In this review, we summarize our current understanding of SARS-CoV enzymes involved in RNA biochemistry, such as the in vitro characterization of a highly active and processive RNA polymerase complex which can associate with methyltransferase and 3'-5' exoribonuclease activities involved in RNA capping, and RNA proofreading, respectively. The recent discoveries reveal fascinating RNA-synthesizing machinery, highlighting the unique position of coronaviruses in the RNA virus world. Copyright © 2014 Elsevier B.V. All rights reserved.

Characterization of rat leydig cell gonadotropin receptor structure by affinity cross-linking

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

Zhang, Q.Y.; Hwang, J.; Menon, K.M.J.

1986-05-01

The gonadotropin receptor from rat leydig cell has been characterized with respect to binding kinetics and physiological regulation. The present study was intended to examine the structure of the receptor. Leydig cell suspension was prepared by either collagenase digestion or by mechanical disruption of the testis. The cells were incubated with /sup 125/I-hCG and the unreacted hCG was removed by centrifugation. The /sup 125/I-hCG was then covalently linked to the cell surface receptor using cleavable (dithiobis (succinimidyl propionate)) and non-cleavable (disuccinimidyl suberate) cross-linking reagents. The extracted cross-linked membrane proteins were resolved on SDS-polyacrylamide gels under reducing and non-reducing conditions andmore » subjected to autoradiographic analysis. Under non-reducing conditions, two labeled species with M/sub r/ = 87,000 and 120,000 were detected. However, only one labeled band was detected under reducing conditions with M/sub r/ = 64,000. The binding of /sup 125/I-hCG to the receptor was inhibited by hCG and LH, but not by a number of peptides and proteins. The data suggest that hCG receptor in leydig cell is an oligomeric complex consisting of four subunits, ..cap alpha cap alpha beta gamma... The ..beta.. and ..gamma.. subunits are each linked to an ..cap alpha.. subunit through disulfide linkage and the hormone binds to each ..cap alpha.. subunit. The two dimers formed (..cap alpha beta cap alpha gamma..) are associated by noncovalent interactions.« less

Consequences of Developmental Exposure to Concentrated Ambient Ultrafine Particle Air Pollution Combined with the Adult Paraquat and Maneb Model of the Parkinson’s Disease Phenotype in Male Mice

PubMed Central

Allen, Joshua L; Liu, Xiufang; Weston, Douglas; Conrad, Katherine; Oberdörster, Günter; Cory-Slechta, Deborah A

2014-01-01

Current evidence suggests suceptibility of both the substantia nigra and striatum to exposure to components of air pollution. Further, air pollution has been associated with increased risk of PD diagnsosis in humans or PD-like pathology in animals. This study examined whether exposure of mice to concentrated ambient ultrafine particles (CAPS; <100 nm diameter) during the first two weeks of life would alter susceptibility to induction of the Parkinson’s disease phenyotype (PDP) in a pesticide-based paraquat and maneb (PQ+MB) model during adulthood utilizing i.p. injections of 10 mg/kg PQ and 30 mg/kg MB 2× per week for 6 weeks. Evidence of CAPS-induced enhancement of the PQ+MB PDP was limited primarily to delayed recovery of locomotor activity 24 post injection of PQ+MB that could be related to alterations in striatal GABA inhibitory function. Absence of more extensive interactions might also reflect the finding that CAPS and PQ+MB appeared to differentially target the nigrostriatal dopamine and amino acid systems, with CAPS impacting striatum and PQ+MB impacting dopamine-glutamate function in midbrain; both CAPS and PQ+MB elevated glutamate levels in these specific regions, consistent with potential excitotoxicity. These findings demonstrate the ability of postnatal CAPS to produce locomotor dysfunction and dopaminergic and glutamateric changes, independent of PQ+MB, in brain regions involved in the PDP. PMID:24486957

Failure Mode Analysis of V-Shaped Pyrotechnically Actuated Valves

NASA Technical Reports Server (NTRS)

Sachdev, Jai S.; Hosangadi, A.; Chenoweth, James D.; Saulsberry, Regor L.; McDougle, Stephen H.

2012-01-01

Current V-shaped stainless steel pyrovalve initiators have rectified many of the deficiencies of the heritage Y-shaped aluminum design. However, a credible failure mode still exists for dual simultaneous initiator (NSI) firings in which low temperatures were detected at the booster cap and less consistent ignition was observed than when a single initiator was fired. In order to asses this issue, a numerical framework has been developed for predicting the flow through pyrotechnically actuated valves. This framework includes a fully coupled solution of the gas-phase equation with a non-equilibrium dispersed phase for solid particles as well as the capability to model conjugate gradient heat transfer to the booster cap. Through a hierarchy of increasingly complex simulations, a hypothesis for the failure mode of the nearly simultaneous dual NSI firings has been proven. The simulations indicate that the failure mode for simultaneous dual NSI firings may be caused by flow interactions between the flame channels. The shock waves from each initiator interact in the booster cavity resulting in a high pressure that prevents the gas and particulate velocity from rising in the booster cap region. This impedes the bulk of the particulate phase from impacting the booster cap and reduces the heat transfer to the booster cap since the particles do not impact it. Heat transfer calculations to the solid metal indicate that gas-phase convective heat transfer may not be adequate by itself and that energy transfer from the particulate phase may be crucial for the booster cap burn through.

The Residual Polar Caps of Mars: Geological Differences and Possible Consequences

NASA Technical Reports Server (NTRS)

Thomas, P. C.; Sullivan, R.; Ingersoll, A. P.; Murray, B. C.; Danielson, G. E.; Herkenhoff, K. E.; Soderblom, L.; Malin, M. C.; Edgett, K. S.; James, P. B.

2000-01-01

The Martian polar regions have been known to have thick layered sequences (presumed to consist of silicates and ice), CO2 seasonal frost, and residual frosts that remain through the summer: H2O in the north, largely CO2 in the south. The relationship of the residual frosts to the underlying layered deposits could not be determined from Viking images. The Mars Orbiter Camera on Mars Global Surveyor has provided a 50-fold increase in resolution that shows more differences between the two poles. The north residual cap surface has rough topography of pits, cracks, and knobs, suggestive of ablational forms. This topography is less than a few meters in height, and grades in to surfaces exposing the layers underneath. In contrast, the south residual cap has distinctive collapse and possibly ablational topography emplaced in four or more layers, each approx. two meters thick. The top surface has polygonal depressions suggestive of thermal contraction cracks. The collapse and erosional forms include circular and cycloidal depressions, long sinuous troughs, and nearly parallel sets of troughs. The distinctive topography occurs throughout the residual cap area, but not outside it. Unconformities exposed in polar layers, or other layered materials, do not approximate the topography seen on the south residual cap. The coincidence of a distinct geologic feature, several layers modified by collapse, ablation, and mass movement with the residual cap indicates a distinct composition and/or climate compared to both the remainder of the south polar layered units and those in the north.

Community‐Academic Partnerships: A Systematic Review of the State of the Literature and Recommendations for Future Research

PubMed Central

MEZA, ROSEMARY D.; BRIKHO, BRIGITTE; NAAF, MEGHAN; ESTABILLO, JASPER A.; GOMEZ, EMILY D.; VEJNOSKA, SARAH F.; DUFEK, SARAH; STAHMER, AUBYN C.; AARONS, GREGORY A.

2016-01-01

Policy Points: Communities, funding agencies, and institutions are increasingly involving community stakeholders as partners in research, to provide firsthand knowledge and insight.Based on our systematic review of major literature databases, we recommend using a single term, community‐academic partnership (CAP), and a conceptual definition to unite multiple research disciplines and strengthen the field.Interpersonal and operational factors that facilitate or hinder the collaborative process have been consistently identified, including “trust among partners” and “respect among partners” (facilitating interpersonal factors) and “excessive time commitment” (hindering operational factor).Once CAP processes and characteristics are better understood, the effectiveness of collaborative partner involvement can be tested. Context Communities, funding agencies, and institutions are increasingly involving community stakeholders as partners in research. Community stakeholders can provide firsthand knowledge and insight, thereby increasing research relevance and feasibility. Despite the greater emphasis and use of community‐academic partnerships (CAP) across multiple disciplines, definitions of partnerships and methodologies vary greatly, and no systematic reviews consolidating this literature have been published. The purpose of this article, then, is to facilitate the continued growth of this field by examining the characteristics of CAPs and the current state of the science, identifying the facilitating and hindering influences on the collaborative process, and developing a common term and conceptual definition for use across disciplines. Methods Our systematic search of 6 major literature databases generated 1,332 unique articles, 50 of which met our criteria for inclusion and provided data on 54 unique CAPs. We then analyzed studies to describe CAP characteristics and to identify the terms and methods used, as well as the common influences on the CAP process and distal outcomes. Findings CAP research spans disciplines, involves a variety of community stakeholders, and focuses on a large range of study topics. CAP research articles, however, rarely report characteristics such as membership numbers or duration. Most studies involved case studies using qualitative methods to collect data on the collaborative process. Although various terms were used to describe collaborative partnerships, few studies provided conceptual definitions. Twenty‐three facilitating and hindering factors influencing the CAP collaboration process emerged from the literature. Outcomes from the CAPs most often included developing or refining tangible products. Conclusions Based on our systematic review, we recommend using a single term, community‐academic partnership, as well as a conceptual definition to unite multiple research disciplines. In addition, CAP characteristics and methods should be reported more systematically to advance the field (eg, to develop CAP evaluation tools). We have identified the most common influences that facilitate and hinder CAPs, which in turn should guide their development and sustainment. PMID:26994713

A 915-MHz antenna for microwave thermal ablation treatment: physical design, computer modeling and experimental measurement.

PubMed

Pisa, S; Cavagnaro, M; Bernardi, P; Lin, J C

2001-05-01

A 915-MHz antenna design that produces specific absorption rate distributions with preferential power deposition in tissues surrounding and including the distal end of the catheter antenna is described. The design features minimal reflected microwave current from the antenna flowing up the transmission line. This cap-choke antenna consists of an annular cap and a coaxial choke which matches the antenna to the coaxial transmission line. The design minimizes heating of the coaxial cable and its performance is not affected by the depth of insertion of the antenna into tissue. The paper provides a comparison of results obtained from computer modeling and experimental measurements made in tissue equivalent phantom materials. There is excellent agreement between numerical modeling and experimental measurement. The cap-choke, matched-dipole type antenna is suitable for intracavitary microwave thermal ablation therapy.

Highly improved passivation of c-Si surfaces using a gradient i a-Si:H layer

NASA Astrophysics Data System (ADS)

Lee, Soonil; Ahn, Jaehyun; Mathew, Leo; Rao, Rajesh; Zhang, Zhongjian; Kim, Jae Hyun; Banerjee, Sanjay K.; Yu, Edward T.

2018-04-01

Surface passivation using intrinsic a-Si:H (i a-Si:H) films plays a key role in high efficiency c-Si heterojunction solar cells. In this study, we demonstrate improved passivation quality using i a-Si:H films with a gradient-layered structure consisting of interfacial, transition, and capping layers deposited on c-Si surfaces. The H2 dilution ratio (R) during deposition was optimized individually for the interfacial and capping layers, which were separated by a transition layer for which R changed gradually between its values for the interfacial and capping layers. This approach yielded a significant reduction in surface carrier recombination, resulting in improvement of the minority carrier lifetime from 1480 μs for mono-layered i a-Si:H passivation to 2550 μs for the gradient-layered passivation approach.

Terahertz antireflection coating enabled by a subwavelength metallic mesh capped with a thin dielectric film

DOE PAGES

Huang, Li; Chen, Hou -Tong; Zeng, Beibei; ...

2016-03-30

Metamaterials/metasurfaces have enabled unprecedented manipulation of electromagnetic waves. Here we present a new design of metasurface structure functioning as antireflection coatings. The structure consists of a subwavelength metallic mesh capped with a thin dielectric layer on top of a substrate. By tailoring the geometric parameters of the metallic mesh and the refractive index and thickness of the capping dielectric film, reflection from the substrate can be completely eliminated at a specific frequency. Compared to traditional methods such as coatings with single- or multi-layer dielectric films, the metasurface antireflection coatings are much thinner and the requirement of index matching is largelymore » lifted. Here, this approach is particularly suitable for antireflection coatings in the technically challenging terahertz frequency range and is also applicable in other frequency regimes.« less

Abscisic acid, xanthoxin and violaxanthin in the caps of gravistimulated maize roots

NASA Technical Reports Server (NTRS)

Feldman, L. J.; Arroyave, N. J.; Sun, P. S.

1985-01-01

The occurrence and distribution of abscisic acid (ABA), xanthoxin (Xa) and the carotenoid violaxanthin (Va) were investigated in root tips of maize (Zea mays L. cv. Merit). In roots grown in the dark, Va and ABA were present in relatively high amounts in the root cap and in low amounts in the adjacent terminal 1.5 mm of the root. Xanthoxin was present in equal concentrations in both regions. In roots exposed to light, the ABA distribution was reversed, with relatively low levels in the root cap and high levels in the adjacent 1.5-mm segment. Light also caused a decrease in Va in both regions of the root and an increase in Xa, especially in the cap. In the maize cultivar used for this work, light is necessary for gravitropic curving. This response occurs within the same time frame as the light-induced ABA redistribution as well as the changes in the levels of Va and Xa. These data are consistent with a role for ABA in root gravitropism and support the proposal that Xa may arise from the turnover of Va.

Investigation of the rates of surface and bulk ROS-generating reactions using indigo dye as an indicator

NASA Astrophysics Data System (ADS)

Anderson, Carly; Clark, Douglas; Graves, David

2014-10-01

We present evidence for the existence of two distinct processes that contribute to the generation of reactive oxygen and nitrogen species (RONS) in liquids exposed to cold atmospheric plasma (CAP) in air. At the plasma-liquid interface, there exists a fast surface reaction zone where RONS from the gas phase interact with species in the liquid. RONS can also be produced by ``slow'' chemical reactions in the bulk liquid, even long after plasma exposure. To separate the effects of these processes, we used indigo dye as an indicator of ROS production; specifically generation of hydroxyl radical. The rate of indigo decolorization while in direct contact with CAP is compared with the expected rate of hydroxyl radical generation at the liquid surface. When added to aqueous solutions after CAP exposure, indigo dye reacts on a time scale consistent with the production of peroxynitrous acid, ONOOH, which is known to decompose to hydroxyl radical below a pH of 6.8. In this study, the CAP used was a air corona discharge plasma run in a positive streamer mode.

Pull-out simulations of a capped carbon nanotube in carbon nanotube-reinforced nanocomposites

NASA Astrophysics Data System (ADS)

Li, Y.; Liu, S.; Hu, N.; Han, X.; Zhou, L.; Ning, H.; Wu, L.; Alamusi, Yamamoto, G.; Chang, C.; Hashida, T.; Atobe, S.; Fukunaga, H.

2013-04-01

Systematic atomic simulations based on molecular mechanics were conducted to investigate the pull-out behavior of a capped carbon nanotube (CNT) in CNT-reinforced nanocomposites. Two common cases were studied: the pull-out of a complete CNT from a polymer matrix in a CNT/polymer nanocomposite and the pull-out of the broken outer walls of a CNT from the intact inner walls (i.e., the sword-in-sheath mode) in a CNT/alumina nanocomposite. By analyzing the obtained relationship between the energy increment (i.e., the difference in the potential energy between two consecutive pull-out steps) and the pull-out displacement, a set of simple empirical formulas based on the nanotube diameter was developed to predict the corresponding pull-out force. The predictions from these formulas are quite consistent with the experimental results. Moreover, the much higher pull-out force for a capped CNT than that of the corresponding open-ended CNT implies a significant contribution from the CNT cap to the interfacial properties of the CNT-reinforced nanocomposites. This finding provides a valuable insight for designing nanocomposites with desirable mechanical properties.

Use of nose cap and fuselage pressure orifices for determination of air data for space shuttle orbiter below supersonic speeds

NASA Technical Reports Server (NTRS)

Larson, T. J.; Siemers, P. M., III

1980-01-01

Wind tunnel pressure measurements were acquired from orifices on a 0.1 scale forebody model of the space shuttle orbiter that were arranged in a preliminary configuration of the shuttle entry air data system (SEADS). Pressures from those and auxiliary orifices were evaluated for their ability to provide air data at subsonic and transonic speeds. The orifices were on the vehicle's nose cap and on the sides of the forebody forward of the cabin. The investigation covered a Mach number range of 0.25 to 1.40 and an angle of attack range from 4 deg. to 18 deg. An air data system consisting of nose cap and forebody fuselage orifices constitutes a complete and accurate air data system at subsonic and transonic speeds. For Mach numbers less than 0.80 orifices confined to the nose cap can be used as a complete and accurate air data system. Air data systems that use only flush pressure orifices can be used to determine basic air data on other aircraft at subsonic and transonic speeds.

A gel-based visual immunoassay for non-instrumental detection of chloramphenicol in food samples.

PubMed

Yuan, Meng; Sheng, Wei; Zhang, Yan; Wang, Junping; Yang, Yijin; Zhang, Shuguang; Goryacheva, Irina Yu; Wang, Shuo

2012-11-02

A gel-based non-instrumental immuno-affinity assay was developed for the rapid screening of chloramphenicol (CAP) in food samples with the limit of detection (LOD) of 1 μg L(-1). The immuno-affinity test column (IATC) consisted of a test layer containing anti-CAP antibody coupled gel, and a control layer with anti-HRP antibody coupled gel. Based on the direct competitive immuno-reaction and the horseradish peroxidase enzymatic reaction, the test results could be evaluated visually. Basically, blue color development represented the negative results, while the absence of color development represented the positive results. In this study, CAP spiked samples of raw milk, pasteurized milk, UHT milk, skimmed milk powder, acacia honey, date honey, fish and shrimp were tested. Little or none sample pretreatment was required for this assay. The whole procedure was completed within 10min. In conclusion, the gel-based immuno-affinity test is a simple, rapid, and promising on-site screening method for CAP residues in food samples, with no instrumental requirement. Copyright © 2012 Elsevier B.V. All rights reserved.

Low reflectance high power RF load

DOEpatents

Ives, R. Lawrence; Mizuhara, Yosuke M.

2016-02-02

A load for traveling microwave energy has an absorptive volume defined by cylindrical body enclosed by a first end cap and a second end cap. The first end cap has an aperture for the passage of an input waveguide with a rotating part that is coupled to a reflective mirror. The inner surfaces of the absorptive volume consist of a resistive material or are coated with a coating which absorbs a fraction of incident RF energy, and the remainder of the RF energy reflects. The angle of the reflector and end caps is selected such that reflected RF energy dissipates an increasing percentage of the remaining RF energy at each reflection, and the reflected RF energy which returns to the rotating mirror is directed to the back surface of the rotating reflector, and is not coupled to the input waveguide. Additionally, the reflector may have a surface which generates a more uniform power distribution function axially and laterally, to increase the power handling capability of the RF load. The input waveguide may be corrugated for HE11 mode input energy.

Low reflectance radio frequency load

DOEpatents

Ives, R. Lawrence; Mizuhara, Yosuke M

2014-04-01

A load for traveling microwave energy has an absorptive volume defined by cylindrical body enclosed by a first end cap and a second end cap. The first end cap has an aperture for the passage of an input waveguide with a rotating part that is coupled to a reflective mirror. The inner surfaces of the absorptive volume consist of a resistive material or are coated with a coating which absorbs a fraction of incident RF energy, and the remainder of the RF energy reflects. The angle of the reflector and end caps is selected such that reflected RF energy dissipates an increasing percentage of the remaining RF energy at each reflection, and the reflected RF energy which returns to the rotating mirror is directed to the back surface of the rotating reflector, and is not coupled to the input waveguide. Additionally, the reflector may have a surface which generates a more uniform power distribution function axially and laterally, to increase the power handling capability of the RF load. The input waveguide may be corrugated for HE11 mode input energy.

Safety of vaccinations in patients with cryopyrin-associated periodic syndromes: a prospective registry based study.

PubMed

Jaeger, Veronika K; Hoffman, Hal M; van der Poll, Tom; Tilson, Hugh; Seibert, Julia; Speziale, Antonio; Junge, Guido; Franke, Kristina; Vritzali, Eleni; Hawkins, Philip N; Kuemmerle-Deschner, Jasmin; Walker, Ulrich A

2017-09-01

Pneumococcal, tetanus and influenza vaccinations are recommended for patients with cryopyrin-associated periodic syndromes (CAPS) when treated with immunosuppressive medication. The aim of this publication is to report the safety of pneumococcal and other vaccinations in CAPS patients. All CAPS patients followed in the β-CONFIDENT (Clinical Outcomes and Safety Registry study of Ilaris patients) registry were analysed if they had received a vaccination. The β-CONFIDENT registry is a global, long-term, prospective, observational registry, capturing and monitoring patients treated with canakinumab. Sixty-eight CAPS patients had received a total of 159 vaccine injections, 107 injections against influenza, 19 pneumococcal vaccinations, 12 against tetanus/diphtheria antigens and 21 other vaccinations. Fourteen per cent of injections had elicited at least one vaccine reaction. All five vaccine-related serious adverse events were associated with pneumococcal vaccination. Vaccine reactions were observed in 70% of pneumococcal vaccinations, compared with 7% in influenza and 17% in tetanus/diphtheria vaccinations. The odds ratios to react to the pneumococcal vaccines compared with influenza and tetanus/diphtheria vaccines were 31.0 (95% CI: 8, 119) and 10.8 (95% CI: 2, 74). Vaccine reactions after pneumococcal vaccinations were more severe and lasted significantly longer (up to 3 weeks) compared with other vaccinations. In two patients, pneumococcal vaccination also elicited symptoms consistent with systemic inflammation due to CAPS reactivation. Pneumococcal vaccines, unlike other vaccines, frequently trigger severe local and systemic inflammation in CAPS patients. Clinicians must balance potential benefits of pneumococcal immunization against safety concerns. The 13-valent pneumococcal conjugate vaccine might be favourable over the polysaccharide vaccine in CAPS patients. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Lipid discordance and carotid plaque in obese patients in primary prevention.

PubMed

Masson, Walter; Siniawski, Daniel; Lobo, Martín; Molinero, Graciela

2018-01-01

Obese patients with lipid discordance (non-HDL cholesterol levels 30mg/dL above the LDL-c value) may have a greater prevalence of carotid atherosclerotic plaque (CAP). Our study objectives were: 1) To assess the prevalence of lipid discordance in a primary prevention population of obese patients; 2) To investigate the association between lipid discordance and presence of CAP. Obese subjects aged >18 years (BMI ≥30kg/m 2 ) with no cardiovascular disease, diabetes, or lipid-lowering treatment from six cardiology centers were included. Lipid discordance was defined when, regardless of the LDL-c level, the non-HDL cholesterol value exceeded the LDL-c value by 30mg/dL. Presence of CAP was identified by ultrasonography. Univariate and multivariate analyses were performed to explore the association between lipid discordance and presence of CAP. The study simple consisted of 325 obese patients (57.2% men; mean age, 52.3 years). Prevalence of lipid discordance was 57.9%. CAP was found in 38.6% of patients, but the proportion was higher in subjects with lipid discordance as compared to those without this lipid pattern (44.4% vs. 30.7%, P=.01). In both the univariate (OR: 1.80; 95% CI: 1.14-2.87; P=.01) and the multivariate analysis (OR: 2.07; 95% CI: 1.22-3.54; P=.007), presence of lipid discordance was associated to an increased probability of CAP. In these obese patients, lipid discordance was associated to greater prevalence of CAP. Evaluation of obese patients with this strategy could help identify subjects with higher residual cardiovascular risk. Copyright © 2017 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

Variability in Pediatric Infectious Disease Consultants' Recommendations for Management of Community-Acquired Pneumonia

PubMed Central

Hersh, Adam L.; Shapiro, Daniel J.; Newland, Jason G.; Polgreen, Philip M.; Beekmann, Susan E.; Shah, Samir S.

2011-01-01

Background Community-acquired pneumonia (CAP) is a common childhood infection. CAP complications, such as parapneumonic empyema (PPE), are increasing and are frequently caused by antibiotic-resistant organisms. No clinical guidelines currently exist for management of pediatric CAP and no published data exist about variations in antibiotic prescribing patterns. Our objectives were to describe variation in CAP clinical management for hospitalized children by pediatric infectious disease consultants and to examine associations between recommended antibiotic regimens and local antibiotic resistance levels. Methods We surveyed pediatric members of the Emerging Infections Network, which consists of 259 pediatric infectious disease physicians. Participants responded regarding their recommended empiric antibiotic regimens for hospitalized children with CAP with and without PPE and their recommendations for duration of therapy. Participants also provided information about the prevalence of penicillin non-susceptible S. pneumoniae and methicillin-resistant S. aureus (MRSA) in their community. Results We received 148 responses (57%). For uncomplicated CAP, respondents were divided between recommending beta-lactams alone (55%) versus beta-lactams in combination with another class (40%). For PPE, most recommended a combination of a beta-lactam plus an anti-MRSA agent, however, they were divided between clindamycin (44%) and vancomycin (57%). The relationship between reported antibiotic resistance and empiric regimen was mixed. We found no relationship between aminopenicillin use and prevalence of penicillin non-suscepetible S. pneumoniae or clindamycin use and clindamycin resistance, however, respondents were more likely to recommend an anti-MRSA agent when MRSA prevalence increased. Conclusions Substantial variability exists in recommendations for CAP management. Development of clinical guidelines via antimicrobial stewardship programs and dissemination of data about local antibiotic resistance patterns represent opportunities to improve care. PMID:21655259

Comparison of Mars Northern Cap Edge Advance and Recession Rates over the Last 6 Mars Years

NASA Astrophysics Data System (ADS)

Titus, T. N.; Cushing, G. E.; Langevin, Y.; Brown, A. J.; Themis Science Team; CRISM Science Team

2011-12-01

The most observable parameter that describes the Mars polar seasonal caps is their size, which has been measured since the days of Herschel. The advance and retreat of the polar cap from year to year may exhibit many clues to help elucidate little understood physical processes. For example, summertime heat storage in the regolith could delay the onset of seasonal CO2 cap formation. The evolution of the seasonal cap could also be directly affected by the thermal inertia of the near-surface regolith and place constraints on the depth of the ice table. Parameterizations of the seasonal cap edges provide useful constraints on atmospheric GCMs and mesoscale models. Longitudinally resolving the cap edges as they advance and retreat constrains the times when zonal means are appropriate and when longitudinal asymmetries make zonal means invalid. These same kinds of parameterizations can also be used when modeling other data that have low spatial resolutions, such as Gamma Ray Spectrometer (GRS )and Neutron Spectrometer (NS) data. By knowing where the cap edge should be, coarse spatial data can correct for subpixel mixing caused by large point-spread functions including both frosted and frost-free areas. The northern cap exhibits a near symmetric retreat, which has been well characterized at visible wavelengths by both telescopic and spacecraft observations. However, the advance of the cap has not been well characterized until the 21st century. Kieffer and Titus (2001) have used zonal means to observe surface temperature and visible bolometric albedo variations with season using MGS/TES. The TES thermal observations show an almost perfectly symmetrical advance; i.e., condensation at consistent latitude across all longitudes, with the most northern edge of the seasonal cap occurring between longitudes 245°E to 265°E and the most southern edge of the seasonal cap occurring between 280°E and 30°E. The advance of the northern cap typically leads the advance of the edge of polar night by 10° of latitude. The northern spring retreat is also nearly symmetric in both visual and thermal observations, and follows the same small asymmetries as seen in the advance. In addition to four Mars years of seasonal observations by TES and MOC, the northern seasonal cap was observed in detail by OMEGA in 2004 and 2006. The bright ring at intermediate temperatures (~ 180 K) observed by TES (Kieffer and Titus, 2001) in early spring is confirmed by OMEGA as resulting from H2O ice frost, with a sublimation front which lags by up to 4° in latitude south of the CO2 ice sublimation front. H2O ice contamination of CO2 ice is ubiquitous in the northern seasonal cap at all stages of its evolution. H2O ice dominates the spectral signatures over most of the seasonal cap after mid-spring. This paper will compare the inter-annual variations in the advance and recession of the Mars northern polar cap over the last 6 Mars years using TES, THEMIS, OMEGA, and CRISM.

Fully Automated Prostate Magnetic Resonance Imaging and Transrectal Ultrasound Fusion via a Probabilistic Registration Metric.

PubMed

Sparks, Rachel; Bloch, B Nicolas; Feleppa, Ernest; Barratt, Dean; Madabhushi, Anant

2013-03-08

In this work, we present a novel, automated, registration method to fuse magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) images of the prostate. Our methodology consists of: (1) delineating the prostate on MRI, (2) building a probabilistic model of prostate location on TRUS, and (3) aligning the MRI prostate segmentation to the TRUS probabilistic model. TRUS-guided needle biopsy is the current gold standard for prostate cancer (CaP) diagnosis. Up to 40% of CaP lesions appear isoechoic on TRUS, hence TRUS-guided biopsy cannot reliably target CaP lesions and is associated with a high false negative rate. MRI is better able to distinguish CaP from benign prostatic tissue, but requires special equipment and training. MRI-TRUS fusion, whereby MRI is acquired pre-operatively and aligned to TRUS during the biopsy procedure, allows for information from both modalities to be used to help guide the biopsy. The use of MRI and TRUS in combination to guide biopsy at least doubles the yield of positive biopsies. Previous work on MRI-TRUS fusion has involved aligning manually determined fiducials or prostate surfaces to achieve image registration. The accuracy of these methods is dependent on the reader's ability to determine fiducials or prostate surfaces with minimal error, which is a difficult and time-consuming task. Our novel, fully automated MRI-TRUS fusion method represents a significant advance over the current state-of-the-art because it does not require manual intervention after TRUS acquisition. All necessary preprocessing steps (i.e. delineation of the prostate on MRI) can be performed offline prior to the biopsy procedure. We evaluated our method on seven patient studies, with B-mode TRUS and a 1.5 T surface coil MRI. Our method has a root mean square error (RMSE) for expertly selected fiducials (consisting of the urethra, calcifications, and the centroids of CaP nodules) of 3.39 ± 0.85 mm.

Translational control of human acetyl-CoA carboxylase 1 mRNA is mediated by an internal ribosome entry site in response to ER stress, serum deprivation or hypoxia mimetic CoCl2.

PubMed

Damiano, Fabrizio; Testini, Mariangela; Tocci, Romina; Gnoni, Gabriele V; Siculella, Luisa

2018-04-01

Acetyl-CoA carboxylase 1 (ACC1) is a cytosolic enzyme catalyzing the rate limiting step in de novo fatty acid biosynthesis. There is mounting evidence showing that ACC1 is susceptible to dysregulation and that it is over-expressed in liver diseases associated with lipid accumulation and in several cancers. In the present study, ACC1 regulation at the translational level is reported. Using several experimental approaches, the presence of an internal ribosome entry site (IRES) has been established in the 5' untranslated region (5' UTR) of the ACC1 mRNA. Transfection experiments with the ACC1 5' UTR inserted in a dicistronic reporter vector show a remarkable increase in the downstream cistron translation, through a cap-independent mechanism. The endoplasmic reticulum (ER) stress condition and the related unfolded protein response (UPR), triggered by treatment with thapsigargin and tunicamycin, cause an increase of the cap-independent translation of ACC1 mRNA in HepG2 cells, despite the overall reduction in global protein synthesis. Other stress conditions, such as serum starvation and incubation with hypoxia mimetic agent CoCl 2 , up-regulate ACC1 expression in HepG2 cells at the translational level. Overall, these findings indicate that the presence of an IRES in the ACC1 5' UTR allows ACC1 mRNA translation in conditions that are inhibitory to cap-dependent translation. A potential involvement of the cap-independent translation of ACC1 in several pathologies, such as obesity and cancer, has been discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

ELEVATION OF C-FLIP IN CASTRATE-RESISTANT PROSTATE CANCER ANTAGONIZES THERAPEUTIC RESPONSE TO ANDROGEN-RECEPTOR TARGETED THERAPY

PubMed Central

McCourt, Clare; Maxwell, Pamela; Mazzucchelli, Roberta; Montironi, Rodolfo; Scarpelli, Marina; Salto-Tellez, Manuel; O’Sullivan, Joe M.; Longley, Daniel B.; Waugh, David J.J.

2012-01-01

Purpose To characterize the importance of cellular Fas-associated death domain (FADD)-like interleukin 1β-converting enzyme (FLICE) inhibitory protein (c-FLIP), a key regulator of caspase 8 (FLICE)-promoted apoptosis, in modulating the response of prostate cancer (CaP) cells to androgen receptor (AR)-targeted therapy. Experimental Design c-FLIP expression was characterized by immunohistochemical analysis of prostatectomy tissue. The functional importance of c-FLIP to survival and modulating response to bicalutamide was studied by molecular and pharmacological interventions. Results c-FLIP expression was increased in high-grade prostatic intra-epithelial neoplasia (HGPIN) and CaP tissue relative to normal prostate epithelium (P<0.001). Maximal c-FLIP expression was detected in castrate-resistant CaP (CRPC) (P<0.001). In vitro, silencing of c-FLIP induced spontaneous apoptosis and increased 22Rv1 and LNCaP cell sensitivity to bicalutamide, determined by flow cytometry, PARP cleavage and caspase activity assays. The histone deacetylase inhibitors (HDACi), droxinostat and SAHA, also down-regulated c-FLIP expression, induced caspase-8 and caspase-3/7 mediated apoptosis and increased apoptosis in bicalutamide-treated cells. Conversely, the elevated expression of c-FLIP detected in the CRPC cell line VCaP underpinned their insensitivity to bicalutamide and SAHA in vitro. However, knockdown of c-FLIP induced spontaneous apoptosis in VCaP cells, indicating its relevance to cell survival and therapeutic resistance. Conclusion c-FLIP reduces the efficacy of AR-targeted therapy and maintains the viability of CaP cells. A combination of HDACi with androgen-deprivation therapy (ADT) may be effective in early-stage disease, using c-FLIP expression as a predictive biomarker of sensitivity. Direct targeting of c-FLIP however may be relevant to enhance the response of existing and novel therapeutics in CRPC. PMID:22623731

Short-Term Hypocaloric High-Fiber and High-Protein Diet Improves Hepatic Steatosis Assessed by Controlled Attenuation Parameter

PubMed Central

Arslanow, Anita; Teutsch, Melanie; Walle, Hardy; Grünhage, Frank; Lammert, Frank; Stokes, Caroline S

2016-01-01

OBJECTIVES: Non-alcoholic fatty liver disease is one of the most prevalent liver diseases and increases the risk of fibrosis and cirrhosis. Current standard treatment focuses on lifestyle interventions. The primary aim of this study was to assess the effects of a short-term low-calorie diet on hepatic steatosis, using the controlled attenuation parameter (CAP) as quantitative tool. METHODS: In this prospective observational study, 60 patients with hepatic steatosis were monitored during a hypocaloric high-fiber, high-protein diet containing 1,000 kcal/day. At baseline and after 14 days, we measured hepatic fat contents using CAP during transient elastography, body composition with bioelectrical impedance analysis, and serum liver function tests and lipid profiles using standard clinical–chemical assays. RESULTS: The median age was 56 years (25–78 years); 51.7% were women and median body mass index was 31.9 kg/m2 (22.4–44.8 kg/m2). After 14 days, a significant CAP reduction (14.0% P<0.001) was observed from 295 dB/m (216–400 dB/m) to 266 dB/m (100–353 dB/m). In parallel, body weight decreased by 4.6% (P<0.001), of which 61.9% was body fat. In addition, liver stiffness (P=0.002), γ-GT activities, and serum lipid concentrations decreased (all P<0.001). CONCLUSIONS: This study shows for the first time that non-invasive elastography can be used to monitor rapid effects of dietary treatment for hepatic steatosis. CAP improvements occur after only 14 days on short-term low-calorie diet, together with reductions of body composition parameters, serum lipids, and liver enzymes, pointing to the dynamics of hepatic lipid turnover. PMID:27311064

Short-Term Hypocaloric High-Fiber and High-Protein Diet Improves Hepatic Steatosis Assessed by Controlled Attenuation Parameter.

PubMed

Arslanow, Anita; Teutsch, Melanie; Walle, Hardy; Grünhage, Frank; Lammert, Frank; Stokes, Caroline S

2016-06-16

Non-alcoholic fatty liver disease is one of the most prevalent liver diseases and increases the risk of fibrosis and cirrhosis. Current standard treatment focuses on lifestyle interventions. The primary aim of this study was to assess the effects of a short-term low-calorie diet on hepatic steatosis, using the controlled attenuation parameter (CAP) as quantitative tool. In this prospective observational study, 60 patients with hepatic steatosis were monitored during a hypocaloric high-fiber, high-protein diet containing 1,000 kcal/day. At baseline and after 14 days, we measured hepatic fat contents using CAP during transient elastography, body composition with bioelectrical impedance analysis, and serum liver function tests and lipid profiles using standard clinical-chemical assays. The median age was 56 years (25-78 years); 51.7% were women and median body mass index was 31.9 kg/m(2) (22.4-44.8 kg/m(2)). After 14 days, a significant CAP reduction (14.0%; P<0.001) was observed from 295 dB/m (216-400 dB/m) to 266 dB/m (100-353 dB/m). In parallel, body weight decreased by 4.6% (P<0.001), of which 61.9% was body fat. In addition, liver stiffness (P=0.002), γ-GT activities, and serum lipid concentrations decreased (all P<0.001). This study shows for the first time that non-invasive elastography can be used to monitor rapid effects of dietary treatment for hepatic steatosis. CAP improvements occur after only 14 days on short-term low-calorie diet, together with reductions of body composition parameters, serum lipids, and liver enzymes, pointing to the dynamics of hepatic lipid turnover.

Specific role of LeMAN2 in the control of seed germination exposed by overexpression of the LeMAN3 gene in tomato plants.

PubMed

Belotserkovsky, Harel; Berger, Yael; Shahar, Ron; Wolf, Shmuel

2007-12-01

Endo-beta-mannanase is one of the key enzymes involved in the hydrolysis of the mannan-rich cell walls of tomato (Solanum lycopersicon) seeds. Two isoforms of endo-beta-mannanase have been characterized in tomato seeds: LeMAN2 is active in the micropylar area prior to germination and LeMAN1 is active after germination in all endosperm cells surrounding the cotyledons. To explore whether general mannanase activity in the endosperm cap is sufficient to promote germination, the gene encoding LeMAN3 was inserted into transgenic tomato plants under the control of a CaMV-35S promoter. Expression of LeMAN3 was evident in the endosperm cap and in the lateral endosperm of the transgenic seeds 10 min after imbibition. An activity test indicated increased activity of endo-beta-mannanase in the transgenic lines relative to the control line in all seed parts, during the first 20 h of imbibition. However, overexpression of LeMAN3 in transgenic seeds inhibited seed germination at both optimal and suboptimal temperatures. Detailed RT-PCR analyses revealed the transcription patterns of the genes encoding the various mannanase isoforms, and indicated a delay in LeMAN2 transcription in the endosperm cap of the transgenic seeds. Interestingly, tissue-print assays indicated similar mannanase activity in the micropylar areas for both transgenic and control seeds. These results indicate that overexpression of active endo-beta-mannanase in the endosperm cap is not sufficient to enable hydrolysis of the cell walls or to promote germination of tomato seeds. Cell-wall hydrolysis in these endosperm cells is under tight control and requires the specific activity of LeMAN2.

Novel photoluminescence enzyme immunoassay based on supramolecular host-guest recognition using L-arginine/6-aza-2-thiothymine-stabilized gold nanocluster.

PubMed

Wang, Youmei; Lu, Minghua; Tang, Dianping

2018-06-30

A new photoluminescence (PL) enzyme immunoassay was designed for sensitive detection of aflatoxin B 1 (AFB 1 ) via an innovative enzyme substrate, 6-aza-2-thiothymine-stabilized gold nanocluster (AAT-AuNC) with L-arginine. The enzyme substrate with strong PL intensity was formed through supramolecular host-guest assembly between guanidine group of L-arginine and AAT capped on the surface of AuNC. Upon arginase introduction, the captured L-arginine was hydrolyzed into ornithine and urea, thus resulting in the decreasing PL intensity. Based on this principle, a novel competitive-type immunoreaction was first carried out on AFB 1 -bovine serum albumin (AFB 1 -BSA) conjugate-coated microplate, using arginase-labeled anti-AFB 1 antibody as the competitor. Under the optimum conditions, the PL intensity increased with the increment of target AFB 1 , and allowed the detection of the analyte at concentrations as low as 3.2 pg mL -1 (ppt). Moreover, L-arginine-AAT-AuNC-based PL enzyme immunoassay afforded good reproducibility and acceptable specificity. In addition, the accuracy of this methodology, referring to commercial AFB 1 ELISA kit, was evaluated to analyze naturally contaminated or spiked peanut samples, giving well-matched results between two methods, thus representing a useful scheme for practical application in quantitative monitoring of mycotoxins in foodstuff. Copyright © 2018 Elsevier B.V. All rights reserved.

Model of turnover kinetics in the lamellipodium: implications of slow- and fast- diffusing capping protein and Arp2/3 complex

NASA Astrophysics Data System (ADS)

McMillen, Laura M.; Vavylonis, Dimitrios

2016-12-01

Cell protrusion through polymerization of actin filaments at the leading edge of motile cells may be influenced by spatial gradients of diffuse actin and regulators. Here we study the distribution of two of the most important regulators, capping protein and Arp2/3 complex, which regulate actin polymerization in the lamellipodium through capping and nucleation of free barbed ends. We modeled their kinetics using data from prior single molecule microscopy experiments on XTC cells. These experiments have provided evidence for a broad distribution of diffusion coefficients of both capping protein and Arp2/3 complex. The slowly diffusing proteins appear as extended ‘clouds’ while proteins bound to the actin filament network appear as speckles that undergo retrograde flow. Speckle appearance and disappearance events correspond to assembly and dissociation from the actin filament network and speckle lifetimes correspond to the dissociation rate. The slowly diffusing capping protein could represent severed capped actin filament fragments or membrane-bound capping protein. Prior evidence suggests that slowly diffusing Apr2/3 complex associates with the membrane. We use the measured rates and estimates of diffusion coefficients of capping protein and Arp2/3 complex in a Monte Carlo simulation that includes particles in association with a filament network and diffuse in the cytoplasm. We consider two separate pools of diffuse proteins, representing fast and slowly diffusing species. We find a steady state with concentration gradients involving a balance of diffusive flow of fast and slow species with retrograde flow. We show that simulations of FRAP are consistent with prior experiments performed on different cell types. We provide estimates for the ratio of bound to diffuse complexes and calculate conditions where Arp2/3 complex recycling by diffusion may become limiting. We discuss the implications of slowly diffusing populations and suggest experiments to distinguish among mechanisms that influence long range transport.

CAPS Simulation Environment Development

NASA Technical Reports Server (NTRS)

Murphy, Douglas G.; Hoffman, James A.

2005-01-01

The final design for an effective Comet/Asteroid Protection System (CAPS) will likely come after a number of competing designs have been simulated and evaluated. Because of the large number of design parameters involved in a system capable of detecting an object, accurately determining its orbit, and diverting the impact threat, a comprehensive simulation environment will be an extremely valuable tool for the CAPS designers. A successful simulation/design tool will aid the user in identifying the critical parameters in the system and eventually allow for automatic optimization of the design once the relationships of the key parameters are understood. A CAPS configuration will consist of space-based detectors whose purpose is to scan the celestial sphere in search of objects likely to make a close approach to Earth and to determine with the greatest possible accuracy the orbits of those objects. Other components of a CAPS configuration may include systems for modifying the orbits of approaching objects, either for the purpose of preventing a collision or for positioning the object into an orbit where it can be studied or used as a mineral resource. The Synergistic Engineering Environment (SEE) is a space-systems design, evaluation, and visualization software tool being leveraged to simulate these aspects of the CAPS study. The long-term goal of the SEE is to provide capabilities to allow the user to build and compare various CAPS designs by running end-to-end simulations that encompass the scanning phase, the orbit determination phase, and the orbit modification phase of a given scenario. Herein, a brief description of the expected simulation phases is provided, the current status and available features of the SEE software system is reported, and examples are shown of how the system is used to build and evaluate a CAPS detection design. Conclusions and the roadmap for future development of the SEE are also presented.

14-3-3η Amplifies Androgen Receptor Actions in Prostate Cancer

PubMed Central

Titus, Mark A.; Tan, Jiann-an; Gregory, Christopher W.; Ford, O. Harris; Subramanian, Romesh R.; Fu, Haian; Wilson, Elizabeth M.; Mohler, James L.; French, Frank S.

2009-01-01

Purpose Androgen receptor (AR) abundance and AR-regulated gene expression in castration-recurrent prostate cancer (CaP) are indicative of AR activation in the absence of testicular androgen. AR transactivation of target genes in castration-recurrent CaP occurs in part through mitogen signaling that amplifies the actions of AR and its coregulators. Herein we report on the role of 14-3-3η in AR action. Experimental Design and Results AR and 14-3-3η co-localized in COS cell nuclei with and without androgen and 14-3-3η promoted AR nuclear localization in the absence of androgen. 14-3-3η interacted with AR in cell-free binding and coimmunoprecipitation assays. In the recurrent human CaP cell line, CWR-R1, native endogenous AR transcriptional activation was stimulated by 14-3-3η at low DHT concentrations and was increased by EGF. Moreover, the DHT and EGF dependent increase in AR transactivation was inhibited by a dominant negative 14-3-3η. In the CWR22 CaP xenograft model, 14-3-3η expression was increased by androgen, suggesting a feed-forward mechanism that potentiates both 14-3-3η and AR actions. 14-3-3η mRNA and protein decreased following castration of tumor bearing mice and increased in tumors of castrate mice after treatment with testosterone. CWR22 tumors that recurred 5 months after castration contained 14-3-3η levels similar to the androgen-stimulated tumors removed before castration. In a human prostate tissue microarray of clinical specimens, 14-3-3η localized with AR in nuclei and the similar amounts expressed in castration-recurrent CaP, androgen-stimulated CaP and benign prostatic hyperplasia were consistent with AR activation in recurrent CaP. Conclusion 14-3-3η enhances androgen and mitogen induced AR transcriptional activity in castration-recurrent CaP. PMID:19996220

Developmental Exposure to Concentrated Ambient Ultrafine Particulate Matter Air Pollution in Mice Results in Persistent and Sex-Dependent Behavioral Neurotoxicity and Glial Activation

PubMed Central

Allen, Joshua L.; Liu, Xiufang; Weston, Douglas; Prince, Lisa; Oberdörster, Günter; Finkelstein, Jacob N.; Johnston, Carl J.; Cory-Slechta, Deborah A.

2014-01-01

The brain appears to be a target of air pollution. This study aimed to further ascertain behavioral and neurobiological mechanisms of our previously observed preference for immediate reward (Allen, J. L., Conrad, K., Oberdorster, G., Johnston, C. J., Sleezer, B., and Cory-Slechta, D. A. (2013). Developmental exposure to concentrated ambient particles and preference for immediate reward in mice. Environ. Health Perspect. 121, 32–38), a phenotype consistent with impulsivity, in mice developmentally exposed to inhaled ultrafine particles. It examined the impact of postnatal and/or adult concentrated ambient ultrafine particles (CAPS) or filtered air on another behavior thought to reflect impulsivity, Fixed interval (FI) schedule-controlled performance, and extended the assessment to learning/memory (novel object recognition (NOR)), and locomotor activity to assist in understanding behavioral mechanisms of action. In addition, levels of brain monoamines and amino acids, and markers of glial presence and activation (GFAP, IBA-1) were assessed in mesocorticolimbic brain regions mediating these cognitive functions. This design produced four treatment groups/sex of postnatal/adult exposure: Air/Air, Air/CAPS, CAPS/Air, and CAPS/CAPS. FI performance was adversely influenced by CAPS/Air in males, but by Air/CAPS in females, effects that appeared to reflect corresponding changes in brain mesocorticolimbic dopamine/glutamate systems that mediate FI performance. Both sexes showed impaired short-term memory on the NOR. Mechanistically, cortical and hippocampal changes in amino acids raised the potential for excitotoxicity, and persistent glial activation was seen in frontal cortex and corpus callosum of both sexes. Collectively, neurodevelopment and/or adulthood CAPS can produce enduring and sex-dependent neurotoxicity. Although mechanisms of these effects remain to be fully elucidated, findings suggest that neurodevelopment and/or adulthood air pollution exposure may represent a significant underexplored risk factor for central nervous system diseases/disorders and thus a significant public health threat even beyond current appreciation. PMID:24690596

Dissection of the antimicrobial and hemolytic activity of Cap18: Generation of Cap18 derivatives with enhanced specificity.

PubMed

Ebbensgaard, Anna; Mordhorst, Hanne; Overgaard, Michael Toft; Aarestrup, Frank Møller; Hansen, Egon Bech

2018-01-01

Due to the rapid emergence of resistance to classical antibiotics, novel antimicrobial compounds are needed. It is desirable to selectively kill pathogenic bacteria without targeting other beneficial bacteria in order to prevent the negative clinical consequences caused by many broad-spectrum antibiotics as well as reducing the development of antibiotic resistance. Antimicrobial peptides (AMPs) represent an alternative to classical antibiotics and it has been previously demonstrated that Cap18 has high antimicrobial activity against a broad range of bacterial species. In this study we report the design of a positional scanning library consisting of 696 Cap18 derivatives and the subsequent screening for antimicrobial activity against Y. ruckeri, A. salmonicida, S. Typhimurium and L. lactis as well as for hemolytic activity measuring the hemoglobin release of horse erythrocytes. We show that the hydrophobic face of Cap18, in particular I13, L17 and I24, is essential for its antimicrobial activity against S. Typhimurium, Y. ruckeri, A. salmonicida, E. coli, P. aeruginosa, L. lactis, L. monocytogenes and E. faecalis. In particular, Cap18 derivatives harboring a I13D, L17D, L17P, I24D or I24N substitution lost their antimicrobial activity against any of the tested bacterial strains. In addition, we were able to generate species-specific Cap18 derivatives by particular amino acid substitutions either in the hydrophobic face at positions L6, L17, I20, and I27, or in the hydrophilic face at positions K16 and K18. Finally, our data showed the proline residue at position 29 to be essential for the inherent low hemolytic activity of Cap18 and that substitution of the residues K16, K23, or G21 by any hydrophobic residues enhances the hemolytic activity. This study demonstrates the potential of generating species-specific AMPs for the selective elimination of bacterial pathogens.

Dione and Rhea seasonal exospheres revealed by Cassini CAPS and INMS

NASA Astrophysics Data System (ADS)

Teolis, B. D.; Waite, J. H.

2016-07-01

A Dione O2 and CO2 exosphere of similar composition and density to Rhea's is confirmed by Cassini spacecraft Ion Neutral Mass Spectrometer (INMS) flyby data. INMS results from three Dione and two Rhea flybys show exospheric spatial and temporal variability indicative of seasonal exospheres, modulated by winter polar gas adsorption and desorption at the equinoxes. Cassini Plasma Spectrometer (CAPS) pickup ion fluxes also show exospheric structure and evolution at Rhea consistent with INMS, after taking into consideration the anticipated charge exchange, electron impact, and photo-ionization rates. Data-model comparisons show the exospheric evolution to be consistent with polar frost diffusion into the surface regolith, which limits surface exposure and loss of the winter frost cap by sputtering. Implied O2 source rates of ∼45(7) × 1021 s-1 at Dione(Rhea) are ∼50(300) times less than expected from known O2 radiolysis yields from ion-irradiated pure water ice measured in the laboratory, ruling out secondary sputtering as a major exospheric contributor, and implying a nanometer scale surface refractory lag layer consisting of concentrated carbonaceous impurities. We estimate ∼30:1(2:1) relative O2:CO2 source rates at Dione(Rhea), consistent with a stoichiometric bulk composition below the lag layer of 0.01(0.13) C atoms per H2O molecule, deriving from endogenic constituents, implanted micrometeoritic organics, and (in particular at Dione) exogenous H2O delivery by E-ring grains. Impact deposition, gardening and vaporization may thereby control the global O2 source rates by fresh H2O ice exposure to surface radiolysis and trapped oxidant ejection.

A highly sensitive detection of chloramphenicol based on chemiluminescence immunoassays with the cheap functionalized Fe3 O4 @SiO2 magnetic nanoparticles.

PubMed

Linyu, Wang; Manwen, Yao; Chengzhi, Fang; Xi, Yao

2017-09-01

A strategy has been applied to chloramphenicol (CAP) detection with chemiluminescence immunoassays (CLIA) based on cheap functionalized Fe 3 O 4 @SiO 2 magnetic nanoparticles (Fe-MNPs). The strategy that bovine serum albumin (BSA) was immobilized on cheap functionalized Fe-MNPs and that the CAP molecules were then immobilized on BSA, avoided the long process of dialysis for preparation of the BSA-CAP conjugates. The samples were detected for both methods that utilized two different kinds of functionalized Fe-MNPs (amine-functionalized Fe 3 O 4 @SiO 2 and carboxylic acid-functionalized Fe 3 O 4 @SiO 2 ). The sensitivities and limits of detection (LODs) of the two methods were obtained and compared based on inhibition curves. The 50% inhibition concentrations (IC 50 ) values of the two methods were about 0.024 ng ml -1 and 0.046 ng ml -1 respectively and LODs were approximately 0.0002 ng ml -1 and 0.001 ng ml -1 respectively. These methods were much more sensitive than that of any traditional enzyme-linked immunosorbent assay (ELISA) previously reported. Therefore, such chemiluminescence methods could be easily adapted for small molecule detection in a variety of foods using Fe-MNPs. Copyright © 2017 John Wiley & Sons, Ltd.

Expression analysis and clinical utility of L-Dopa decarboxylase (DDC) in prostate cancer.

PubMed

Avgeris, Margaritis; Koutalellis, Georgios; Fragoulis, Emmanuel G; Scorilas, Andreas

2008-10-01

L-Dopa decarboxylase (DDC) is a pyridoxal 5'-phosphate-dependent enzyme that was found to be involved in many malignancies. The aim of this study was to investigate the mRNA expression levels of DDC in prostate tissues and to evaluate its clinical utility in prostate cancer (CaP). Total RNA was isolated from 118 tissue specimens from benign prostate hyperplasia (BPH) and CaP patients and a highly sensitive quantitative real-time RT-PCR (qRT-PCR) method for DDC mRNA quantification has been developed using the SYBR Green chemistry. LNCaP prostate cancer cell line was used as a calibrator and GAPDH as a housekeeping gene. DDC was found to be overexpressed, at the mRNA level, in the specimens from prostate cancer patients, in comparison to those from benign prostate hyperplasia patients (p<0.001). Logistic regression and ROC analysis have demonstrated that the DDC expression has significant discriminatory value between CaP and BPH (p<0.001). DDC expression status was compared with other established prognostic factors, in prostate cancer. High expression levels of DDC were found more frequently in high Gleason's score tumors (p=0.022) as well as in advanced stage patients (p=0.032). Our data reveal the potential of DDC expression, at the mRNA level, as a novel biomarker in prostate cancer.

Hormonal regulation of hepatic glycogenolysis in the carp, Cyprinus carpio

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

Janssens, P.A.; Lowrey, P.

1987-04-01

Carp (Cyprinus carpio) liver maintained normal glycogen content and enzyme complement for several days in organ culture. Epinephrine-stimulated glycogenolysis, phosphorylase activation, and cyclic AMP (cAMP) accumulation in a concentration-dependent manner with EC/sub 50/s of 100, 100, and 500 nM, respectively. These actions were blocked by the ..beta..-adrenergic antagonist, propranolol, but not by the ..cap alpha..-adrenergic antagonist phentolamine. Glycogenolysis and tissue cAMP were uninfluenced by 10/sup -6/ M arginine vasotocin, arginine vasopressin, lysine vasotocin, lysine vasopressin, mesotocin, or oxytocin, but were slightly increased by 10/sup -5/ M isotocin and slightly decreased by 10/sup -6/ M angiotensin II. (/sup 125/I)-iodocyanopindolol (ICP), amore » ..beta..-adrenergic ligand, bound to isolated carp liver membranes with a K/sub D/ of 83 pM. Maximum binding of 45 fmol/mg protein was at 600 pM. Propranolol, isoprenaline, epinephrine, phenylephrine, norepinephrine, and phenoxybenzamine displaced ICP with K/sub D/s of 100 nM, 2, 20, 20, 60, and 200 ..mu..M, respectively. The ..cap alpha..-adrenergic antagonists, yohimbine and prazosin, showed no specific binding. These data provide evidence that catecholamines act via ..beta..-adrenergic receptors in carp liver and that ..cap alpha..-adrenergic receptors are not present. Vasoactive peptides play no significant role in regulation of carp liver glycogenolysis.« less

A Sensitive and Robust High-Throughput Screening Assay for Inhibitors of the Chikungunya Virus nsP1 Capping Enzyme.

PubMed

Bullard-Feibelman, Kristen M; Fuller, Benjamin P; Geiss, Brian J

2016-01-01

Chikungunya virus (CHIKV) is a mosquito-borne Alphavirus that causes severe and debilitating disease symptoms. Alarmingly, transmission rates of CHIKV have increased dramatically over the last decade resulting in 1.7 million suspected cases in the Western hemisphere alone. There are currently no antivirals for treatment of CHIKV infection and novel anti-alphaviral compounds are badly needed. nsP1 is the alphavirus protein responsible for the methyltransferase and guanylyltransferase activities necessary for formation of the 5' type 0 cap structure added to newly formed viral RNA. Formation of this cap depends on nsP1 binding GTP and transferring a methylated GMP to nascent viral RNA. We have developed a fluorescence polarization-based assay that monitors displacement of a fluorescently-labeled GTP analog in real time. Determining the relative affinities of 15 GTP analogs for nsP1 GTP revealed important structural aspects of GTP that will inform identification of inhibitors able to outcompete GTP for the nsP1 binding site. Validation of the assay for HTS was completed and a secondary orthogonal assay that measures guanylation activity was developed in order to evaluate hits from future drug screens. This platform provides an avenue for identification of potent nsP1 inhibitors, which would potentially provide compounds capable of treating disease caused by CHIKV infection.

Effects of dietary saw palmetto on the prostate of transgenic adenocarcinoma of the mouse prostate model (TRAMP).

PubMed

Wadsworth, Teri L; Worstell, Teresa R; Greenberg, Norman M; Roselli, Charles E

2007-05-01

Several of the proposed mechanisms for the actions of the liposterolic extract of saw palmetto (SPE) are exerted on known risk factors for prostate cancer (CaP). This study investigated whether SPE could prevent the progression of CaP in a transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Two different doses of SPE designed to deliver 50 mg/kg/day SPE and 300 mg/kg/day SPE were administered in a custom diet to TRAMP mice for 12 or 24 weeks. Body and organ weights were used to evaluate toxicity, and radioimmunoassay was used to measure plasma and tissue androgen levels to monitor effects of SPE on 5alpha reductase activity. Prostate tissues were evaluated histologically to determine the effect of treatment on tumor grade, cell proliferation, and apoptosis. Treatment with 300 mg/kg/day SPE from 4 to 24 weeks of age significantly reduced the concentration of 5alpha-dihydrotestosterone (DHT) in the prostate and resulted in a significant increase in apoptosis and significant decrease in pathological tumor grade and frank tumor incidence. Dietary supplementation with SPE may be effective in controlling CaP tumorigenesis. SPE suppression of prostatic DHT levels lends support to the hypothesis that inhibition of the enzyme 5alpha-reductase is a mechanism of action of this substance. (c) 2007 Wiley-Liss, Inc.

Deregulation of miRNAs Contributes to Development and Progression of Prostate Cancer

DTIC Science & Technology

2012-09-01

p14ARF gene were co-transfected with miR-125b into LNCaP cells. Cotransfection resulted in approximately 50% reduction of the enzyme activity (Fig...Figure3. Downregulation of miR-125b activity induces apoptosis in p53-null CaP cells. A) Western blot analysis of p14ARF and...miR-124-mediated downregulation of the AR affects the AR activity , both AR- positive LNCaP and C4-2B were treated with miR-124 mimic. Western blot

Trithiocarbonates: exploration of a new head group for HDAC inhibitors.

PubMed

Dehmel, Florian; Ciossek, Thomas; Maier, Thomas; Weinbrenner, Steffen; Schmidt, Beate; Zoche, Martin; Beckers, Thomas

2007-09-01

Inhibition of histone deacetylases class I/II enzymes is a new, promising approach for cancer therapy. In the present study, we disclose a new structural class of HDAC inhibitors with the trithiocarbonate motif. A clear structure-activity-relationship was obtained for the cap-linker motif and the putative Zn(2+) complexing head group. Selected analogs display potent inhibition of HDAC enzymatic activity and a cellular potency comparable to that of suberoylanilide hydroxamic acid (SAHA), recently approved for treatment of patients with advanced cutaneous T-cell lymphoma.

Structure of 2C-Methyl-D-erythritol-2,4-cyclodiphosphate Synthase from Shewanella oneidensis at 1.6 angstrom: Identification of Farnesyl pyrophosphate Trapped in a Hydrophobic Cavity

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

Ni, Shuisong; Robinson, Howard; Marsing, Gregory C.

2004-11-01

1. Introduction Enzymes in the non-mevalonate pathway for isoprenoid synthesis have gained recent attention because of their potential value as targets for antibiotic drug development. 2C-methyl-D-erythritol-2,4 cyclophosphate (MECDP) synthase is the fifth enzyme in the seven enzyme non-mevalonate pathway for synthesis of isopentenyl diphosphate. Four groups have published structures of MECDP synthase at resolutions varying from 1.6Å to 2.8Å, either in the presence or absence of substrate from Escherichia coli (Richard et al., 2002; Kemp et al., 2002; Steinbacher et al., 2002) or from Thermus thermophilus (Kishida et al., 2003). Among these structures, the protein always exists as a homotrimermore » either with a crystallographic or a non-crystallographic three-fold symmetry axis and an active site formed in a cleft between adjacent monomers. While the overall shape of the proteins is highly similar among these structures, each of the four reported structures contain different combinations of metal ions in the active site including a Zn2+ ion only (Steinbacher et al., 2002), a Mn2+ ion only (Richard et al., 2002), Zn2+ and Mn2+ ions (Kemp et al., 2002) or two Mg2+ ions (Kishida et al., 2003). Furthermore, two of the structures are reported to contain a hydrophobic channel along the three-fold symmetry axis that is capped by a cluster of three arginine side chains (one from each monomer) at one end of the cavity and a cluster of three glutamic acid side chains (one from each monomer) at the other side of the cavity. In a 1.8Å resolution structure, Kemp et al. (2002) reported a sulfate ion coordinated to the arginine cap and solvent trapped in a hydrophobic cavity. In a lower 2.8Å resolution structure, Richard et al. (2002) concluded that geranyl diphosphate, GPP, was most likely trapped by the arginine cap and hydrophobic cavity (Richard et al., 2002), however, the low resolution of the data together with the presence of the crystallographic symmetry axis prohibited a definitive analysis of the identity and mode of binding of the bound molecule. Kishida et al. (2003) reported that no cavity existed in a 1.6Å structure of the SO3437 homolog from Thermus thermophilus, presumably due to tighter packing of the protein from the thermophilic organism. Steinbacher et al. (2002) make no description of a hydrophobic cavity in a lower resolution (2.5-3.2Å) of the Escherichia coli protein. Here, we report a high-resolution (1.6Å) structure of MECDP synthase from Shewanella oneidensis in the absence of substrate in the active site. We provide unambiguous data that confirms the presence of Zn2+ in one of the metal binding sites and observe what appears to be farnesyl diphosphate (FPP) bound in the hydrophobic cavity along the non-crystallographic three-fold symmetry axis of the homotrimer. The high-resolution structure clarifies the mode of binding of the pyrophosphate of FPP in the arginine cluster that caps the hydrophobic cavity.« less

System Performance Simulations of the RatCAP Awake Rat Brain Scanner

NASA Astrophysics Data System (ADS)

Shokouhi, S.; Vaska, P.; Schlyer, D. J.; Stoll, S. P.; Villanueva, A.; Kriplani, A.; Woody, C. L.

2005-10-01

The capability to create high quality images from data acquired by the Rat Conscious Animal PET tomograph (RatCAP) has been evaluated using modified versions of the PET Monte Carlo code Simulation System for Emission Tomography (SimSET). The proposed tomograph consists of lutetium oxyorthosilicate (LSO) crystals arranged in 12 4 /spl times/ 8 blocks. The effects of the RatCAPs small ring diameter (/spl sim/40 mm) and its block detector geometry on image quality for small animal studies have been investigated. Since the field of view will be almost as large as the ring diameter, radial elongation artifacts due to parallax error are expected to degrade the spatial resolution and thus the image quality at the edge of the field of view. In addition to Monte Carlo simulations, some preliminary results of experimentally acquired images in both two-dimensional (2-D) and 3-D modes are presented.

Real-time monitoring of corks' water absorption using laser speckle temporal correlation

NASA Astrophysics Data System (ADS)

Nassif, Rana; Abou Nader, Christelle; Pellen, Fabrice; Le Jeune, Bernard; Le Brun, Guy; Abboud, Marie

2015-08-01

Physical and mechanical properties of cork allow it solving many types of problems and make it suitable for a wide range of applications. Our objective consists into studying cork's water absorption by analyzing the dynamic speckle field using the temporal correlation method. Experimental results show that the medium was inert at first with the absence of activity, and as the cap cork was more and more immersed into water, the presence of the activity becomes more significant. This temporal parameter revealed the sensibility of biospeckle method to monitor the amount of absorbed water by cork caps.

Low-temperature field ion microscopy of carbon nanotubes

NASA Astrophysics Data System (ADS)

Ksenofontov, V. A.; Gurin, V. A.; Gurin, I. V.; Kolosenko, V. V.; Mikhailovskij, I. M.; Sadanov, E. V.; Mazilova, T. I.; Velikodnaya, O. A.

2007-10-01

The methods of high-resolution field ion microscopy with sample cooling to liquid helium temperature are used in a study of the products of gas-phase catalytic pyrolysis of hydrocarbons in the form of graphitized fibers containing carbon nanotubes. Full atomic resolution of the end cap of closed carbon nanotubes is achieved for the first time. It is found that the atomic structure of the tops of the caps of subnanometer carbon tubes consists predominantly of hexagonal rings. A possible reason for the improvement of the resolution of field ion images of nanotubes upon deep cooling is discussed.

Rotating cathode device for molten salt bath

NASA Astrophysics Data System (ADS)

1983-11-01

The invention relates to a rotating cathode device for molten salt baths used to prepare metallic titanium or aluminum and the like by electrolysis of molten salts. The rotating cathode device is described. It is a cyclindrical cathode mounted on a rotating spindle, made of a lightweight material and mounted in such a way as to avoid thermal strain between the rotational shaft and the cylindrical cathode. At least one of the upper and lower ends of the cylindrical cathode are closed by a cap and a seal consisting of an inorganic fiber composite in the area between the cap and the cathode.

Modeling the total dust production of Enceladus from stochastic charge equilibrium and simulations

NASA Astrophysics Data System (ADS)

Meier, Patrick; Motschmann, Uwe; Schmidt, Jürgen; Spahn, Frank; Hill, Thomas W.; Dong, Yaxue; Jones, Geraint H.; Kriegel, Hendrik

2015-12-01

Negatively and positively charged nano-sized ice grains were detected in the Enceladus plume by the Cassini Plasma Spectrometer (CAPS). However, no data for uncharged grains, and thus for the total amount of dust, are available. In this paper we estimate this population of uncharged grains based on a model of stochastic charging in thermodynamic equilibrium and on the assumption of quasi-neutrality in the plasma-dust system. This estimation is improved upon by combining simulations of the dust component of the plume and simulations for the plasma environment into one self-consistent model. Calibration of this model with CAPS data provides a total dust production rate of about 12 kg s-1, including larger dust grains up to a few microns in size. We find that the fraction of charged grains dominates over that of the uncharged grains. Moreover, our model reproduces densities of both negatively and positively charged nanograins measured by Cassini CAPS. In Enceladus' plume ion densities up to ~104cm-3 are required by the self-consistent model, resulting in an electron depletion of about 50% in the plasma, because electrons are attached to the negatively charged nanograins. These ion densities correspond to effective ionization rates of about 10-7s-1, which are about two orders of magnitude higher than expected.

Dried calcium alginate/magnetite spheres: a new support for chromatographic separations and enzyme immobilization

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

Burns, M.A.; Kvesitadze, G.I.; Graves, D.J.

1985-02-01

Dried spheres made from an alginate solution containing magnetite particles have excellent potential as a support for enzyme immobilization and chromatographic applications. The beads were found to be much stronger than gels such as polyacrylamide and dextran, indicating that high flow rates and pressures could be used in column separations. The support withstood not only temperatures of up to 120/sup 0/C, but also most pH values and common solvents. While some solutions, such as phosphate buffers, dissolved the spheres, stabilization with Tyzor TE eliminated this problem. The physical properties of the beads include a glasslike density of 2.2 g/mL, excellentmore » sphericity, low porosity, and a narrow size distribution. The magnetite present in the support allows the beads to be used for magnetic separations such as high gradient magnetic filtration. Their high degree of microroughness provides a large exposed surface area for enzyme and ligand binding. Mixed Actinomyces fradiae proteases and Aspergillus niger ..cap alpha..-amylase, two enzymes representative of classes which attack large substrates, were immobilized on the bead's surface with high activity and stability. A cyanuric dye which can be used in chromatographic applications (Cibacron Blue F3GA) was also readily coupled to the surface of this support with good yield.« less

Ir Spectral Mapping of the Martian South Polar Residual CAP Using Crism

NASA Astrophysics Data System (ADS)

Campbell, Jacqueline; Sidiropoulos, Panagiotis; Muller, Jan-Peter

2016-06-01

Polycyclic aromatic hydrocarbons (PAHs) are considered to be important in theories of abiogenesis (Allamandola, 2011) . There is evidence that PAHs have been detected on two icy Saturnian satellites using the Visual and Infrared Mapping Spectrometer (VIMS) on the Cassini spacecraft (Cruikshank et al., 2007). The hypothesised presence of PAHs in Mars south polar cap has not been systematically examined even though the Mars south polar cap may allow the preservation of organic molecules that are typically destroyed at the Martian surface by UV radiation (Dartnell et al. 2012). This hypothesis is supported by recent analyses of South Polar Residual Cap (SPRC) structural evolution (Thomas et al., 2009) that suggest the possibility that seasonal and long term sublimation may excavate dust particles from within the polar ice. Periodic sublimation is believed to be responsible for the formation of so-called "Swiss Cheese Terrain", a unique surface feature found only in the Martian south polar residual cap consisting of flat floored, circular depressions (Byrne, 2009). We show the first examples of work towards the detection of PAHs in Swiss Cheese Terrain, using data from the Compact Reconnaissance Imaging Spectrometer for Mars (CRISM), on board NASA's Mars Reconnaissance Orbiter (MRO). CRISM is designed to search for mineralogical indications of past and present water, thus providing extensive coverage of the south polar cap. In this work, we discuss whether CRISM infrared spectra can be used to detect PAHs in Swiss Cheese Terrain and demonstrate a number of maps showing shifts in spectral profiles over the SPRC.

Conversion of Nuclear Waste into Nuclear Waste Glass: Experimental Investigation and Mathematical Modeling

DOE PAGES

Hrma, Pavel

2014-12-18

The melter feed, slurry, or calcine charged on the top of a pool of molten glass forms a floating layer of reacting material called the cold cap. Between the cold-cap top, which is covered with boiling slurry, and its bottom, where bubbles separate it from molten glass, the temperature changes by up to 1000 K. The processes that occur over this temperature interval within the cold cap include liberation of gases, conduction and consumption of heat, dissolution of quartz particles, formation and dissolution of intermediate crystalline phases, and generation of foam and gas cavities. These processes have been investigated usingmore » thermal analyses, optical and electronic microscopies, x-ray diffraction, as well as other techniques. Properties of the reacting feed, such as heat conductivity and density, were measured as functions of temperature. Investigating the structure of quenched cold caps produced in a laboratory-scale melter complemented the crucible studies. The cold cap consists of two main layers. The top layer contains solid particles dissolving in the glass-forming melt and open pores through which gases are escaping. The bottom layer contains bubbly melt or foam where bubbles coalesce into larger cavities that move sideways and release the gas to the atmosphere. The feed-to-glass conversion became sufficiently understood for representing the cold-cap processes via mathematical models. These models, which comprise heat transfer, mass transfer, and reaction kinetics models, have been developed with the final goal to relate feed parameters to the rate of glass melting.« less

Correlations between gravitropic curvature and auxin movement across gravistimulated roots of Zea mays

NASA Technical Reports Server (NTRS)

Young, L. M.; Evans, M. L.; Hertel, R.

1990-01-01

We compared the kinetics of auxin redistribution across the caps of primary roots of 2-day-old maize (Zea mays, cv Merit) seedlings with the time course of gravitropic curvature. [3H] indoleacetic acid was applied to one side of the cap in an agar donor and radioactivity moving across the cap was collected in an agar receiver applied to the opposite side. Upon gravistimulation the roots first curved upward slightly, then returned to the horizontal and began curving downward, reaching a final angle of about 67 degrees. Movement of label across the caps of gravistimulated roots was asymmetric with preferential downward movement (ratio downward/upward = ca. 1.6, radioactivity collected during the 90 min following beginning of gravistimulation). There was a close correlation between the development of asymmetric auxin movement across the root cap and the rate of curvature, with both values increasing to a maximum and then declining as the roots approached the final angle of curvature. In roots preadapted to gravity (alternate brief stimulation on opposite flanks over a period of 1 hour) the initial phase of upward curvature was eliminated and downward bending began earlier than for controls. The correlation between asymmetric auxin movement and the kinetics of curvature also held in comparisons between control and preadapted roots. Both downward auxin transport asymmetry and downward curvature occurred earlier in preadapted roots than in controls. These findings are consistent with suggestions that the root cap is not only the site of perception but also the location of the initial redistribution of effectors that ultimately leads to curvature.

Cyclic alternating pattern and interictal epileptiform discharges during morning sleep after sleep deprivation in temporal lobe epilepsy.

PubMed

Giorgi, Filippo Sean; Maestri, Michelangelo; Guida, Melania; Carnicelli, Luca; Caciagli, Lorenzo; Ferri, Raffaele; Bonuccelli, Ubaldo; Bonanni, Enrica

2017-08-01

Sleep deprivation (SD) increases the occurrence of interictal epileptiform discharges (IED) compared to basal EEG in temporal lobe epilepsy (TLE). In adults, EEG after SD is usually performed in the morning after SD. We aimed to evaluate whether morning sleep after SD bears additional IED-inducing effects compared with nocturnal physiological sleep, and whether changes in sleep stability (described by the cyclic alternating pattern-CAP) play a significant role. Adult patients with TLE underwent in-lab night polysomnography (n-PSG) and, within 7days from n-PSG, they underwent also a morning EEG after night SD (SD-EEG). We included only TLE patients in which both recordings showed IED. SD-EEG consisted of waking up patients at 2:00 AM and performing video EEG at 8:00 AM. For both recordings, we obtained the following markers for the first sleep cycle: IED/h (Spike Index, SI), sleep macrostructure, microstructure (NREM CAP rate; A1, A2 and A3 Indices), and SI association with CAP variables. The macrostructure of the first sleep cycle was similar in n-PSG and morning SD-EEG, whereas CAP rate and SI were significantly higher in SD-EEG. SI increase was selectively associated with CAP phases. SD increases the instability of morning recovery sleep compared with n-PSG, and particularly enhances CAP A1 phases, which are associated with the majority of IED. Thus, higher instability of morning recovery sleep may account at least in part for the increased IED yield in SD-EEG in TLE patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Novel dense CO2 technique for beta-galactosidase immobilization in polystyrene microchannels.

PubMed

Leclair Ellis, Jeffrey; Tomasko, David L; Dehghani, Fariba

2008-03-01

In this study we design new fabrication techniques and demonstrate the potential of using dense CO2 for facilitating crucial steps in the fabrication of polymeric lab-on-a-chip microdevices by embedding biomolecules at temperatures well below the polymer's glass transition temperature (T(g)). These new techniques are environmentally friendly and done without the use of a clean room. Carbon dioxide at 40 degrees C and between 4.48 and 6.89 MPa was used to immobilize the biologically active molecule, beta-galactosidase (beta-gal), on the surface of polystyrene microchannels. To our knowledge, this is the first time dense CO2 has been used to directly immobilize an enzyme in a microchannel. beta-gal activity was maintained and shown via a fluorescent reaction product, after enzyme immobilization and microchannel capping by the designed fabrication steps at 40 degrees C and pressures up to 6.89 MPa.

Recognition and invasion of human erythrocytes by malarial parasites: contribution of sialoglycoproteins to attachment and host specificity

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

Friedman, M.J.; Blankenberg, T.; Sensabaugh, G.

1984-05-01

The receptivity of human erythrocytes to invasion by Plasmodium falciparum merozoites can be decreased by neuraminidase or trypsin treatment, an observation that supports a role for the erythrocyte sialoglycoproteins (glycophorins) in invasion. We have found that ..cap alpha../sub 1/-acid glycoprotein (AGP), added to in vitro cultures, can restore invasion of enzyme-treated human erythrocytes. AGP is structurally different from the glycophorins although it does carry 12% sialic acid. Its ability to restore receptivity to desialylated cells is dependent on its sialic acid complement, its concentration, and its binding to the erythrocyte surface. We present evidence that AGP forms a bridge betweenmore » the merozoite and the enzyme-treated erythrocyte that allows the stronger and more complex interactions of invasion to proceed. We suggest that the glycophorins play the same role on the surface of the intact erythrocyte. 31 references, 3 figures, 6 tables.« less

Dust aerosols above the south polar cap of Mars as seen by OMEGA

NASA Astrophysics Data System (ADS)

Vincendon, M.; Langevin, Y.; Poulet, F.; Bibring, J.-P.; Gondet, B.; Jouglet, D.; Omega Team

2008-08-01

The time evolution of atmospheric dust at high southern latitudes on Mars has been determined using observations of the south seasonal cap acquired in the near infrared (1-2.65 μm) by OMEGA/Mars Express in 2005. Observations at different solar zenith angles and one EPF sequence demonstrate that the reflectance in the 2.64 μm saturated absorption band of the surface CO 2 ice is mainly due to the light scattered by aerosols above most places of the seasonal cap. We have mapped the total optical depth of dust aerosols in the near-IR above the south seasonal cap of Mars from mid-spring to early summer with a time resolution ranging from one day to one week and a spatial resolution of a few kilometers. The optical depth above the south perennial cap is determined on a longer time range covering southern spring and summer. A constant set of optical properties of dust aerosols is consistent with OMEGA observations during the analyzed period. Strong variations of the optical depth are observed over small horizontal and temporal scales, corresponding in part to moving dust clouds. The late summer peak in dust opacity observed by Opportunity in 2005 propagated to the south pole contrarily to that observed in mid spring. This may be linked to evidence for dust scavenging by water ice-rich clouds circulating at high southern latitudes at this season.

Self-Sealing Wet Chemistry Cell for Field Analysis

NASA Technical Reports Server (NTRS)

Beegle, Luther W.; Soto, Juancarlos; Lasnik, James; Roark, Shane

2012-01-01

In most analytical investigations, there is a need to process complex field samples for the unique detection of analytes, especially when detecting low concentration organic molecules that may identify extraterrestrial life. Wet chemistry based instruments are the techniques of choice for most laboratory- based analysis of organic molecules due to several factors including less fragmentation of fragile biomarkers, and ability to concentrate target species resulting in much lower limits of detection. Development of an automated wet chemistry preparation system that can operate autonomously on Earth and is also designed to operate under Martian ambient conditions will demonstrate the technical feasibility of including wet chemistry on future missions. An Automated Sample Processing System (ASPS) has recently been developed that receives fines, extracts organics through solvent extraction, processes the extract by removing non-organic soluble species, and delivers sample to multiple instruments for analysis (including for non-organic soluble species). The key to this system is a sample cell that can autonomously function under field conditions. As a result, a self-sealing sample cell was developed that can autonomously hermetically seal fines and powder into a container, regardless of orientation of the apparatus. The cap is designed with a beveled edge, which allows the cap to be self-righted as the capping motor engages. Each cap consists of a C-clip lock ring below a crucible O-ring that is placed into a groove cut into the sample cap.

CURB-65 Score is Equal to NEWS for Identifying Mortality Risk of Pneumonia Patients: An Observational Study.

PubMed

Brabrand, Mikkel; Henriksen, Daniel Pilsgaard

2018-06-01

The CURB-65 score is widely implemented as a prediction tool for identifying patients with community-acquired pneumonia (cap) at increased risk of 30-day mortality. However, since most ingredients of CURB-65 are used as general prediction tools, it is likely that other prediction tools, e.g. the British National Early Warning Score (NEWS), could be as good as CURB-65 at predicting the fate of CAP patients. To determine whether NEWS is better than CURB-65 at predicting 30-day mortality of CAP patients. This was a single-centre, 6-month observational study using patients' vital signs and demographic information registered upon admission, survival status extracted from the Danish Civil Registration System after discharge and blood test results extracted from a local database. The study was conducted in the medical admission unit (MAU) at the Hospital of South West Jutland, a regional teaching hospital in Denmark. The participants consisted of 570 CAP patients, 291 female and 279 male, median age 74 (20-102) years. The CURB-65 score had a discriminatory power of 0.728 (0.667-0.789) and NEWS 0.710 (0.645-0.775), both with good calibration and no statistical significant difference. CURB-65 was not demonstrated to be significantly statistically better than NEWS at identifying CAP patients at risk of 30-day mortality.

Introducing Co-Activation Pattern Metrics to Quantify Spontaneous Brain Network Dynamics

PubMed Central

Chen, Jingyuan E.; Chang, Catie; Greicius, Michael D.; Glover, Gary H.

2015-01-01

Recently, fMRI researchers have begun to realize that the brain's intrinsic network patterns may undergo substantial changes during a single resting state (RS) scan. However, despite the growing interest in brain dynamics, metrics that can quantify the variability of network patterns are still quite limited. Here, we first introduce various quantification metrics based on the extension of co-activation pattern (CAP) analysis, a recently proposed point-process analysis that tracks state alternations at each individual time frame and relies on very few assumptions; then apply these proposed metrics to quantify changes of brain dynamics during a sustained 2-back working memory (WM) task compared to rest. We focus on the functional connectivity of two prominent RS networks, the default-mode network (DMN) and executive control network (ECN). We first demonstrate less variability of global Pearson correlations with respect to the two chosen networks using a sliding-window approach during WM task compared to rest; then we show that the macroscopic decrease in variations in correlations during a WM task is also well characterized by the combined effect of a reduced number of dominant CAPs, increased spatial consistency across CAPs, and increased fractional contributions of a few dominant CAPs. These CAP metrics may provide alternative and more straightforward quantitative means of characterizing brain network dynamics than time-windowed correlation analyses. PMID:25662866

The interdigitating loop of the enolase superfamily as a specificity binding determinant or 'flying buttress'.

PubMed

Bearne, Stephen L

2017-05-01

Enzymes of the enolase superfamily (ENS) are mechanistically diverse, yet share a common partial reaction (abstraction of the α-proton from a carboxylate substrate). While the catalytic machinery responsible for the deprotonation reaction has been conserved, divergent evolution has led to numerous ENS members that catalyze different overall reactions. This rich functional diversity has made the ENS an excellent model system for developing the approaches necessary to validate enzyme function. However, enzymes of the ENS also share a common bidomain structure ((β/α) 7 β-barrel domain and α+β capping domain) which makes validation of function from structural information challenging. This review presents a comparative survey of the structural data obtained over the past decade for enzymes from all seven subgroups that comprise the ENS. Of the seven ENS subgroups (enolase, mandelate racemase (MR), muconate lactonizing enzyme, β-methylaspartate ammonia lyase, d-glucarate dehydratase, d-mannonate dehydratase (ManD), and galactarate dehydratase 2), only enzymes of the MR and ManD subgroups exhibit an additional feature of structural complexity-an interdigitating loop. This loop emanates from one protomer of a homodimeric pair and penetrates into the adjacent, symmetry-related protomer to either contribute a binding determinant to the active site of the adjacent protomer, or act as a 'flying buttress' to support residues of the active site. The analysis presented in this review suggests that the interdigitating loop is the only gross structural element that permits functional distinction between ENS subgroups at the tertiary level of protein structure. Copyright © 2017 Elsevier B.V. All rights reserved.

Crystal structure of tannase from Lactobacillus plantarum.

PubMed

Ren, Bin; Wu, Mingbo; Wang, Qin; Peng, Xiaohong; Wen, Hua; McKinstry, William J; Chen, Qianming

2013-08-09

Tannins are water-soluble polyphenolic compounds in plants. Hydrolyzable tannins are derivatives of gallic acid (3,4,5-trihydroxybenzoic acid) or its meta-depsidic forms that are esterified to polyol, catechin, or triterpenoid units. Tannases are a family of esterases that catalyze the hydrolysis of the galloyl ester bond in hydrolyzable tannins to release gallic acid. The enzymes have found wide applications in food, feed, beverage, pharmaceutical, and chemical industries since their discovery more than a century ago, although little is known about them at the molecular level, including the details of the catalytic and substrate binding sites. Here, we report the first three-dimensional structure of a tannase from Lactobacillus plantarum. The enzyme displays an α/β structure, featured by a large cap domain inserted into the classical serine hydrolase fold. A catalytic triad was identified in the structure, which is composed of Ser163, His451, and Asp419. During the binding of gallic acid, the carboxyl group of the molecule forges hydrogen-bonding interactions with the catalytic triad of the enzyme while the three hydroxyl groups make contacts with Asp421, Lys343, and Glu357 to form another hydrogen-bonding network. Mutagenesis studies demonstrated that these residues are indispensable for the activity of the enzyme. Structural studies of the enzyme in complex with a number of substrates indicated that the interactions at the galloyl binding site are the determinant force for the binding of substrates. The single galloyl binding site is responsible for the esterase and depsidase activities of the enzyme. Copyright © 2013 Elsevier Ltd. All rights reserved.

Comparative analysis of length of stay, total costs, and treatment success between intravenous moxifloxacin 400 mg and levofloxacin 750 mg among hospitalized patients with community-acquired pneumonia.

PubMed

Friedman, Howard; Song, Xue; Crespi, Simone; Navaratnam, Prakash

2009-01-01

This study aimed to evaluate the length of stay (LOS), costs, and treatment consistency among patients hospitalized with community-acquired pneumonia (CAP) initially treated with intravenous (IV) moxifloxacin 400 mg or IV levofloxacin 750 mg. Adults with CAP receiving IV moxifloxacin or IV levofloxacin for > or =3 days were identified in the Premier Perspective comparative database. Primary outcomes were LOS and costs. Secondary outcomes included treatment consistency, which was defined as 1) no additional IV moxifloxacin or levofloxacin after > or =1 day off study drug; 2) no switch to another IV antibiotic; and 3) no addition of another IV antibiotic. A total of 7720 patients met inclusion criteria (6040 receiving moxifloxacin; 1680 receiving levofloxacin). Propensity matching created two cohorts (1300 patients each) well matched for demographic, clinical, hospital, and payor characteristics. Before the patients were matched, mean LOS (5.87 vs. 5.46 days; P = 0.0004) and total costs per patient ($7302 vs. $6362; P < 0.0001) were significantly greater with moxifloxacin. After the patients were matched, mean LOS (5.63 vs. 5.51 days; P = 0.462) and total costs ($6624 vs. $6473; P = 0.476) were comparable in both cohorts. Treatment consistency was higher for moxifloxacin before (81.0% vs. 78.9%; P = 0.048) and after matching (82.8% vs. 78.0%; P = 0.002). In-hospital treatment of CAP with IV moxifloxacin 400 mg or IV levofloxacin 750 mg was associated with similar hospital LOS and costs in propensity-matched cohorts.

Total duration of antimicrobial therapy in veterans hospitalized with uncomplicated pneumonia: Results of a national medication utilization evaluation.

PubMed

Madaras-Kelly, Karl J; Burk, Muriel; Caplinger, Christina; Bohan, Jefferson G; Neuhauser, Melinda M; Goetz, Matthew Bidwell; Zhang, Rongping; Cunningham, Francesca E

2016-12-01

Practice guidelines recommend the shortest duration of antimicrobial therapy appropriate to treat uncomplicated pneumonia be prescribed to reduce the emergence of resistant pathogens. A national evaluation was conducted to assess the duration of therapy for pneumonia. Retrospective medication utilization evaluation. Thirty Veterans Affairs medical centers. Inpatients discharged with a diagnosis of pneumonia. A manual review of electronic medical records of inpatients discharged with uncomplicated community-acquired pneumonia (CAP) or healthcare-associated pneumonia (HCAP) was conducted. Appropriate CAP therapy duration was defined as at least 5 days, and up to 3 additional days beginning the first day the patient achieved clinical stability criteria; the appropriate HCAP therapy duration was defined as 8 days. The duration of antimicrobial therapy for intravenous (IV) and oral (PO) inpatient administration, PO therapy dispensed upon discharge, Clostridium difficile infection (CDI), hospital readmission, and death rates were measured. Of 3881 pneumonia admissions, 1739 met inclusion criteria (CAP [n = 1195]; HCAP [n = 544]). Overall, 13.9% of patients (CAP [6.9%], HCAP [29.0%]) received therapy duration consistent with guideline recommendations. The median (interquartile range) days of therapy were 4 days (3-6 days), 1 day (0-3 days), and 6 days (4-8 days) for inpatient IV, inpatient PO, and outpatient PO antimicrobials, respectively. CDI was rare but more common in patients who received therapy duration consistent with guidelines. Therapy duration was not associated with the readmission or mortality rate. Antimicrobials were commonly prescribed for a longer duration than guidelines recommend. The majority of excessive therapy was completed upon discharge, identifying the need for strategies to curtail unnecessary use postdischarge. Journal of Hospital Medicine 2015;11:832-839. © 2015 Society of Hospital Medicine. © 2016 Society of Hospital Medicine.

Intranet-based quality improvement documentation at the Veterans Affairs Maryland Health Care System.

PubMed

Borkowski, A; Lee, D H; Sydnor, D L; Johnson, R J; Rabinovitch, A; Moore, G W

2001-01-01

The Pathology and Laboratory Medicine Service of the Veterans Affairs Maryland Health Care System is inspected biannually by the College of American Pathologists (CAP). As of the year 2000, all documentation in the Anatomic Pathology Section is available to all staff through the VA Intranet. Signed, supporting paper documents are on file in the office of the department chair. For the year 2000 CAP inspection, inspectors conducted their document review by use of these Web-based documents, in which each CAP question had a hyperlink to the corresponding section of the procedure manual. Thus inspectors were able to locate the documents relevant to each question quickly and efficiently. The procedure manuals consist of 87 procedures for surgical pathology, 52 procedures for cytopathology, and 25 procedures for autopsy pathology. Each CAP question requiring documentation had from one to three hyperlinks to the corresponding section of the procedure manual. Intranet documentation allows for easier sharing among decentralized institutions and for centralized updates of the laboratory documentation. These documents can be upgraded to allow for multimedia presentations, including text search for key words, hyperlinks to other documents, and images, audio, and video. Use of Web-based documents can improve the efficiency of the inspection process.

Pull-out simulations of a capped carbon nanotube in carbon nanotube-reinforced nanocomposites

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

Li, Y.; Liu, S.; Hu, N.

2013-04-14

Systematic atomic simulations based on molecular mechanics were conducted to investigate the pull-out behavior of a capped carbon nanotube (CNT) in CNT-reinforced nanocomposites. Two common cases were studied: the pull-out of a complete CNT from a polymer matrix in a CNT/polymer nanocomposite and the pull-out of the broken outer walls of a CNT from the intact inner walls (i.e., the sword-in-sheath mode) in a CNT/alumina nanocomposite. By analyzing the obtained relationship between the energy increment (i.e., the difference in the potential energy between two consecutive pull-out steps) and the pull-out displacement, a set of simple empirical formulas based on themore » nanotube diameter was developed to predict the corresponding pull-out force. The predictions from these formulas are quite consistent with the experimental results. Moreover, the much higher pull-out force for a capped CNT than that of the corresponding open-ended CNT implies a significant contribution from the CNT cap to the interfacial properties of the CNT-reinforced nanocomposites. This finding provides a valuable insight for designing nanocomposites with desirable mechanical properties.« less

Biochemical characterization and structural analysis of a new cold-active and salt-tolerant esterase from the marine bacterium Thalassospira sp.

PubMed

De Santi, Concetta; Leiros, Hanna-Kirsti S; Di Scala, Alessia; de Pascale, Donatella; Altermark, Bjørn; Willassen, Nils-Peder

2016-05-01

A gene encoding an esterase, ThaEst2349, was identified in the marine psychrophilic bacterium Thalassospira sp. GB04J01. The gene was cloned and overexpressed in E. coli as a His-tagged fusion protein. The recombinant enzyme showed optimal activity at 45 °C and the thermal stability displayed a retention of 75 % relative activity at 40 °C after 2 h. The optimal pH was 8.5 but the enzyme kept more than 75 % of its maximal activity between pH 8.0 and 9.5. ThaEst2349 also showed remarkable tolerance towards high concentrations of salt and it was active against short-chain p-nitrophenyl esters, displaying optimal activity with the acetate. The enzyme was tested for tolerance of organic solvents and the results are suggesting that it could function as an interesting candidate for biotechnological applications. The crystal structure of ThaEst2349 was determined to 1.69 Å revealing an asymmetric unit containing two chains, which also is the biological unit. The structure has a characteristic cap domain and a catalytic triad comprising Ser158, His285 and Asp255. To explain the cold-active nature of the enzyme, we compared it against thermophilic counterparts. Our hypothesis is that a high methionine content, less hydrogen bonds and less ion pairs render the enzyme more flexible at low temperatures.

Molecular modelling and quantum biochemistry computations of a naturally occurring bioremediation enzyme: Alkane hydroxylase from Pseudomonas putida P1.

PubMed

de Sousa, B G; Oliveira, J I N; Albuquerque, E L; Fulco, U L; Amaro, V E; Blaha, C A G

2017-10-01

Many species of bacteria involved in degradation of n-alkanes have an important constitutional metabolic enzyme, the alkane hydroxylase called AlkB, specialized in the conversion of hydrocarbons molecules that can be used as carbon and/or energy source. This enzyme plays an important role in the microbial degradation of oil, chlorinated hydrocarbons, fuel additives, and many other compounds. A number of these enzymes has been biochemically characterized in detail because the potential of alkane hydroxylases to catalyse high added-value reactions is widely recognized. Nevertheless, the industrial and process bioremediation application of them is restricted, owing to their complex biochemistry, challenging process requirements, and the limited number of their three-dimensional structures. Furthermore, AlkB has great potential as biocatalysts for selective transformation of a wide range of chemically inert unreactive alkanes into reactive chemical precursors that can be used as tools for bioremediation and bioprocesses. Aiming to understand the possible ways the AlkB enzyme Pseudomonas putida P1 interacts with octane, octanol and 1-octyne, we consider its suitable biochemical structure taking into account a 3-D homology modelling. Besides, by using a quantum chemistry computational model based on the density functional theory (DFT), we determine possible protein-substrate interaction regions measured by means of its binding energy simulated throughout the Molecular Fractionation with Conjugated Caps (MFCC) approach. Copyright © 2017 Elsevier Inc. All rights reserved.

Cryopyrin-associated periodic syndromes: development of a patient-reported outcomes instrument to assess the pattern and severity of clinical disease activity.

PubMed

Hoffman, Hal M; Wolfe, Frederick; Belomestnov, Pavel; Mellis, Scott J

2008-09-01

Development of an instrument for characterization of symptom patterns and severity in patients with cryopyrin-associated periodic syndromes (CAPS). Two generations of daily health assessment forms (DHAFs) were evaluated in this study. The first-generation DHAF queried 11 symptoms. Analyses of results obtained with that instrument identified five symptoms included in a revised second-generation DHAF that was tested for internal consistency and test-retest reliability. This DHAF was also assessed during the initial portion of a phase 3 clinical study of CAPS treatment. Forty-eight CAPS patients provided data for the first-generation DHAFs. Five symptoms (rash, fever, joint pain, eye redness/pain, and fatigue) were included in the revised second-generation DHAF. Symptom severity was highly variable during all study phases with as many as 89% of patients reporting at least one symptom flare, and percentages of days with flares reaching 58% during evaluation of the second-generation instrument. Mean composite key symptom scores (KSSs) computed during evaluation of the second-generation DHAF correlated well with Physician's Global Assessment of Disease Activity (r=0.91, p<0.0001) and patient reports of limitations of daily activities (r=0.68, p<0.0001). Test-retest reliability and Cronbach's alpha's were high (0.93 and 0.94, respectively) for the second-generation DHAF. Further evaluation of this DHAF during a baseline period and placebo treatment in a phase 3 clinical study of CAPS patients indicated strong correlations between baseline KSS and Physician's Global Assessment of Disease Activity. Cronbach's alpha's at baseline and test-retest reliability were also high. Potentially important study limitations include small sample size, the lack of a standard tool for CAPS symptom assessment against which to validate the DHAF, and no assessment of the instrument's responsivity to CAPS therapy. The DHAF is a new instrument that may be useful for capturing symptom patterns and severity in CAPS patients and monitoring responses to therapies for these conditions.

The X-ray Crystal Structures of Human {alpha}-Phosphomannomutase 1 Reveal the Structural Basis of Congenital Disorder of Glycosylation Type 1a

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

Silvaggi,N.; Zhang, C.; Lu, Z.

2006-01-01

Carbohydrate-deficient glycoprotein syndrome type 1a (CDG-1a) is a congenital disease characterized by severe defects in nervous system development. It is caused by mutations in alpha -phosphomannomutase (of which there are two isozymes, {alpha}-PMM1 and {alpha}-PPM2). Here we report the X-ray crystal structures of human {alpha}-PMM1 in the open conformation, with and without the bound substrate, {alpha}-D-mannose 1-phosphate. {alpha}-PMM1, like most Haloalkanoic Acid Dehalogenase Superfamily (HADSF) members, consists of two domains, the cap and core, which open to bind substrate and then close to provide a solvent exclusive environment for catalysis. The substrate phosphate group is observed at a positively chargedmore » site of the cap domain, rather than at the core domain phosphoryl-transfer site defined by the D19 nucleophile and Mg{sup 2+} cofactor. This suggests that substrate binds first to the cap and then is swept into the active site upon cap closure. The orientation of the acid/base residue D21 suggests that {alpha}-PMM uses a different method of protecting the aspartylphosphate from hydrolysis than the HADSF member {beta}-phosphoglucomutase. It is hypothesized that the electrostatic repulsion of positive charges at the interface of the cap and core domains stabilizes {alpha}-PMM1 in the open conformation, and that the negatively charged substrate binds to the cap, thereby facilitating its closure over the core domain. The two isozymes {alpha}-PMM1 and {alpha}-PMM2 are shown to have a conserved active-site structure and to display similar kinetic properties. Analysis of the known mutation sites in the context of the structures reveals the genotype-phenotype relationship underlying CDG-1a.« less

Development and Evaluation of a Contrast Sensitivity Perimetry Test for Patients with Glaucoma

PubMed Central

Hot, Aliya; Dul, Mitchell W.; Swanson, William H.

2008-01-01

Purpose To design a contrast sensitivity perimetry (CSP) protocol that decreases variability in glaucomatous defects while maintaining good sensitivity to glaucomatous loss. Methods Twenty patients with glaucoma and 20 control subjects were tested with a CSP protocol implemented on a monitor-based testing station. In the protocol 26 locations were tested over the central visual field with Gabor patches with a peak spatial frequency of 0.4 cyc/deg and a two-dimensional spatial Gaussian envelope, with most of the energy concentrated within a 4° circular region. Threshold was estimated by a staircase method. Patients and 10 age-similar control subjects were also tested on conventional automated perimetry (CAP), with the 24−2 pattern with the SITA Standard testing strategy. The neuroretinal rim area of the patients was measured with a retinal tomograph (Retina Tomograph II [HRT]; Heidelberg Engineering, Heidelberg, Germany). A Bland-Altman analysis of agreement was used to assess test–retest variability, compare depth of defect shown by the two perimetric tests, and investigate the relations between contrast sensitivity and neuroretinal rim area. Results Variability showed less dependence on defect depth for CSP than for CAP (z = 9.3, P < 0.001). Defect depth was similar for CAP and CSP when averaged by quadrant (r = 0.26, P > 0.13). The relation between defect depth and rim area was more consistent with CSP than with CAP (z = 9, P < 0.001). Conclusions The implementation of CSP was successful in reducing test–retest variability in glaucomatous defects. CSP was in general agreement with CAP in terms of depth of defect and was in better agreement than CAP with HRT-determined rim area. PMID:18378580

Genetic polymorphism and prostate cancer aggressiveness: a case-only study of 1,536 GWAS and candidate SNPs in African-Americans and European-Americans.

PubMed

Bensen, Jeannette T; Xu, Zongli; Smith, Gary J; Mohler, James L; Fontham, Elizabeth T H; Taylor, Jack A

2013-01-01

Genome-wide association studies have established a number of replicated single nucleotide polymorphisms (SNPs) for susceptibility to prostate cancer (CaP), but it is unclear whether these susceptibility SNPs are also associated with disease aggressiveness. This study evaluates whether such replication SNPs or other candidate SNPs are associated with CaP aggressiveness in African-American (AA) and European-American (EA) men. A 1,536 SNP panel which included 34 genome-wide association study (GWAS) replication SNPs, 38 flanking SNPs, a set of ancestry informative markers, and SNPs in candidate genes and other areas was genotyped in 1,060 AA and 1,087 EA men with incident CaP from the North Carolina-Louisiana Prostate Cancer Project (PCaP). Tests for association were conducted using ordinal logistic regression with a log-additive genotype model and a 3-category CaP aggressiveness variable. Four GWAS replication SNPs (rs2660753, rs13254738, rs10090154, rs2735839) and seven flanking SNPs were associated with CaP aggressiveness (P < 0.05) in three genomic regions: One at 3p12 (EA), seven at 8q24 (5 AA, 2 EA), and three at 19q13 at the kallilkrein-related peptidase 3 (KLK3) locus (two AA, one AA and EA). The KLK3 SNPs also were associated with serum prostate-specific antigen (PSA) levels in AA (P < 0.001) but not in EA. A number of the other SNPs showed some evidence of association but none met study-wide significance levels after adjusting for multiple comparisons. Some replicated GWAS susceptibility SNPs may play a role in CaP aggressiveness. However, like susceptibility, these associations are not consistent between racial groups. Copyright © 2012 Wiley Periodicals, Inc.

Genetic polymorphism and prostate cancer aggressiveness: A case-only study of 1536 GWAS and candidate SNPs in African Americans and European Americans

PubMed Central

Bensen, Jeannette T.; Xu, Zongli; Smith, Gary J.; Mohler, James L.; Fontham, Elizabeth T.H.; Taylor, Jack A.

2012-01-01

BACKGROUND Genome-wide association studies have established a number of replicated single nucleotide polymorphisms (SNPs) for susceptibility to prostate cancer (CaP), but it is unclear whether these susceptibility SNPs are also associated with disease aggressiveness. This study evaluates whether such replication SNPs or other candidate SNPs are associated with CaP aggressiveness in African-American (AA) and European-American (EA) men. METHODS A 1,536 SNP panel which included 34 genome-wide association study (GWAS) replication SNPs, 38 flanking SNPs, a set of ancestry informative markers, and SNPs in candidate genes and other areas was genotyped in 1,060 AA and 1,087 EA men with incident CaP from the North Carolina-Louisiana Prostate Cancer Project (PCaP). Tests for association were conducted using ordinal logistic regression with a log-additive genotype model and a 3-category CaP aggressiveness variable. RESULTS 4 GWAS replication SNPs (rs2660753, rs13254738, rs10090154, rs2735839) and 7 flanking SNPs were associated with CaP aggressiveness (P<0.05) in 3 genomic regions: one at 3p12 (EA), 7 at 8q24 (5 AA, 2 EA), and 3 at 19q13 at the kallilkrein-related peptidase 3 (KLK3) locus (2 AA, 1 AA and EA). The KLK3 SNPs also were associated with serum prostate-specific antigen (PSA) levels in AA (p < 0.001) but not in EA. A number of the other SNPs showed some evidence of association but none met study-wide significance levels after adjusting for multiple comparisons. CONCLUSIONS Some replicated GWAS susceptibility SNPs may play a role in CaP aggressiveness. However, like susceptibility, these associations are not consistent between racial groups. PMID:22549899

Development and evaluation of a contrast sensitivity perimetry test for patients with glaucoma.

PubMed

Hot, Aliya; Dul, Mitchell W; Swanson, William H

2008-07-01

To design a contrast sensitivity perimetry (CSP) protocol that decreases variability in glaucomatous defects while maintaining good sensitivity to glaucomatous loss. Twenty patients with glaucoma and 20 control subjects were tested with a CSP protocol implemented on a monitor-based testing station. In the protocol 26 locations were tested over the central visual field with Gabor patches with a peak spatial frequency of 0.4 cyc/deg and a two-dimensional spatial Gaussian envelope, with most of the energy concentrated within a 4 degrees circular region. Threshold was estimated by a staircase method: Patients and 10 age-similar control subjects were also tested on conventional automated perimetry (CAP), with the 24-2 pattern with the SITA Standard testing strategy. The neuroretinal rim area of the patients was measured with a retinal tomograph (Retina Tomograph II [HRT]; Heidelberg Engineering, Heidelberg, Germany). A Bland-Altman analysis of agreement was used to assess test-retest variability, compare depth of defect shown by the two perimetric tests, and investigate the relations between contrast sensitivity and neuroretinal rim area. Variability showed less dependence on defect depth for CSP than for CAP (z = 9.3, P < 0.001). Defect depth was similar for CAP and CSP when averaged by quadrant (r = 0.26, P > 0.13). The relation between defect depth and rim area was more consistent with CSP than with CAP (z = 9, P < 0.001). The implementation of CSP was successful in reducing test-retest variability in glaucomatous defects. CSP was in general agreement with CAP in terms of depth of defect and was in better agreement than CAP with HRT-determined rim area.

Directly Driven Ion Outflow

NASA Technical Reports Server (NTRS)

Elliott, H. A.; Comfort, R. H.; Craven, P. D.; Moore, T. E.; Russell, C. T.; Rose, M. Franklin (Technical Monitor)

2001-01-01

We examine ionospheric outflows in the high altitude magnetospheric polar cap during the POLAR satellite's apogee on April 19, 1996 using the Thermal Ion Dynamics Experiment (TIDE) instrument. The elevated levels of O(+) observed in this pass may be due to the geophysical conditions during and prior to the apogee pass. In addition to the high abundance of O(+) relative to H(+), several other aspects of this data are noteworthy. We observe relationships between the density, velocity, and temperature which appear to be associated with perpendicular heating and the mirror force, rather than adiabatic expansion. The H(+) outflow is at a fairly constant flux which is consistent with being source limited by charge exchange at lower altitudes. Local centrifugal acceleration in the polar cap is found to be insufficient to account for the main variations we observe in the outflow velocity. The solar wind speed is high during this pass approximately 700 kilometers per second, and there are Alfve'n waves present in the solar wind such that the solar wind speed and IMF Bx are correlated. In this pass both the H(+) and O(+) outflow velocities correlate with both the solar wind speed and IMF fluctuations. Polar cap magnetometer and Hydra electron data show the same long period wave structure as found in the solar wind and polar cap ion outflow. In addition, the polar cap Poynting flux along the magnetic field direction correlates well with the H(+) temperature (R=0.84). We conclude that the solar wind can drive polar cap ion outflow particularly during polar squalls by setting up a parallel drop that is tens of eV which then causes the ion outflow velocity of O(+) and H(+), the electrons, and magnetic perturbations to vary in a similar fashion.

E2C mechanism of elimination reactions. IX. Secondary deuterium isotope effects on rates of bimolecular reactions in alicyclic systems

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

Cook, D.

1976-06-11

Secondary ..cap alpha..-deuterium isotope effects on the rates of NBu/sub 4/OAc and NBu/sub 4/Cl promoted bimolecular reactions (E2 and SN2) of cyclohexyl tosylate and cyclohexyl bromide have been studied. The E2 reactions, previously categorized as E2C-like, show ..cap alpha..-deuterium isotope effects in the range 1.14--1.22, while the related SN2 reactions give values in the range 1.05--1.08. The discrepancy in the magnitude of the ..cap alpha..-deuterium isotope effect for the E2 and SN2 processes is consistent with the view that E2C-like reactions use ''looser'' transition states than those used in the concurrent SN2 reactions. While the reported ..cap alpha..-d isotope effectsmore » do not provide positive evidence to support the idea that the base interacts with C/sub ..cap alpha../ in the E2 transition states of the reactions studied, neither do they substantiate claims for dismissal of the concept. A comparison of the secondary ..gamma..-deuterium and ..beta..'-deuterium isotope effects arising in the reaction of cyclohexyl tosylate with NBu/sub 4/OAc in acetone indicates the two isotope effects to be of equivalent magnitude (k/sub ..beta..'-d/k/sub ..gamma..-d/ = 0.98). This observation can only be rationalized for this reaction in terms of a transition state structure in which there is extensive double bond development. It provides compelling evidence against the involvement of any transition state structure which accommodates extensive positive charge development at C/sub ..cap alpha../.« less

Real life management of community-acquired Pneumonia in adults in the Gulf region and comparison with practice guidelines: a prospective study.

PubMed

Mahboub, Bassam; Al Zaabi, Ashraf; Al Ali, Ola Mohamed; Ahmed, Raees; Niederman, Michael S; El-Bishbishi, Rania

2015-09-30

Very few data exist on the management of community-acquired pneumonia (CAP) in patients admitted to hospitals in the Gulf region. The objectives of this study were to describe treatment patterns for CAP in 38 hospitals in five Gulf countries (United Arab Emirates, Kuwait, Bahrain, Oman, and Qatar) and to compare the findings to the most recent Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) guidelines. This was a prospective, observational study conducted between January 2009 and February 2011. Adult patients hospitalised (excluding intensive care units) for CAP and subsequently discharged were included. Data were collected retrospectively at hospital discharge, and prospectively during two follow-up visits. Data on medical history, mortality-risk scores, diagnostic criteria, antibiotic treatment, isolated pathogens and clinical and radiographic outcomes were collected. Care practices were compared to the IDSA/ATS guidelines. A total of 684 patients were included. The majority (82.9 %) of patients were classified as low risk for mortality (pneumonia severity index II and III). The majority of patients fulfilled criteria for treatment success at discharge, although only 77.6 % presented a normalised leukocyte count. Overall, the management of CAP in Gulf countries is in line with the IDSA/ATS guidelines. This applied to the diagnosis of CAP, to the identification of high-risk CAP patients, to the identification of etiologic agent responsible for CAP and to the type of treatment despite the fact that combinations of antimicrobial agents were not consistent with the guidelines in 10 % of patients. In all patients, information about Gram's staining was not captured as recommended by the IDSA/ATS and in the majority of patients (>85 %) chest radiography was not systematically performed at the post-discharge follow-up visits. The management of CAP in the Gulf region is globally in line with current IDSA/ATS guidelines, although rates of pathogen characterisation and post-discharge follow-up need to be improved. Compliance with established guidelines should be encouraged in order to improve the management of the disease in this region.

Developmental exposure to concentrated ambient ultrafine particulate matter air pollution in mice results in persistent and sex-dependent behavioral neurotoxicity and glial activation.

PubMed

Allen, Joshua L; Liu, Xiufang; Weston, Douglas; Prince, Lisa; Oberdörster, Günter; Finkelstein, Jacob N; Johnston, Carl J; Cory-Slechta, Deborah A

2014-07-01

The brain appears to be a target of air pollution. This study aimed to further ascertain behavioral and neurobiological mechanisms of our previously observed preference for immediate reward (Allen, J. L., Conrad, K., Oberdorster, G., Johnston, C. J., Sleezer, B., and Cory-Slechta, D. A. (2013). Developmental exposure to concentrated ambient particles and preference for immediate reward in mice. Environ. Health Perspect. 121, 32-38), a phenotype consistent with impulsivity, in mice developmentally exposed to inhaled ultrafine particles. It examined the impact of postnatal and/or adult concentrated ambient ultrafine particles (CAPS) or filtered air on another behavior thought to reflect impulsivity, Fixed interval (FI) schedule-controlled performance, and extended the assessment to learning/memory (novel object recognition (NOR)), and locomotor activity to assist in understanding behavioral mechanisms of action. In addition, levels of brain monoamines and amino acids, and markers of glial presence and activation (GFAP, IBA-1) were assessed in mesocorticolimbic brain regions mediating these cognitive functions. This design produced four treatment groups/sex of postnatal/adult exposure: Air/Air, Air/CAPS, CAPS/Air, and CAPS/CAPS. FI performance was adversely influenced by CAPS/Air in males, but by Air/CAPS in females, effects that appeared to reflect corresponding changes in brain mesocorticolimbic dopamine/glutamate systems that mediate FI performance. Both sexes showed impaired short-term memory on the NOR. Mechanistically, cortical and hippocampal changes in amino acids raised the potential for excitotoxicity, and persistent glial activation was seen in frontal cortex and corpus callosum of both sexes. Collectively, neurodevelopment and/or adulthood CAPS can produce enduring and sex-dependent neurotoxicity. Although mechanisms of these effects remain to be fully elucidated, findings suggest that neurodevelopment and/or adulthood air pollution exposure may represent a significant underexplored risk factor for central nervous system diseases/disorders and thus a significant public health threat even beyond current appreciation. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Mass balance of Mars' residual south polar cap from CTX images and other data

NASA Astrophysics Data System (ADS)

Thomas, P. C.; Calvin, W.; Cantor, B.; Haberle, R.; James, P. B.; Lee, S. W.

2016-04-01

Erosion of pits in the residual south polar cap (RSPC) of Mars concurrent with deposition and fluctuating cap boundaries raises questions about the mass balance and long term stability of the cap. Determining a mass balance by measurement of a net gain or loss of atmospheric CO2 by direct pressure measurements (Haberle, R.M. et al. [2014]. Secular climate change on Mars: An update using one Mars year of MSL pressure data. American Geophysical Union (Fall). Abstract 3947), although perhaps the most direct method, has so far given ambiguous results. Estimating volume changes from imaging data faces challenges, and has previously been attempted only in isolated areas of the cap. In this study we use 6 m/pixel Context Imager (CTX) data from Mars year 31 to map all the morphologic units of the RSPC, expand the measurement record of pit erosion rates, and use high resolution images to place limits on vertical changes in the surface of the residual cap. We find the mass balance in Mars years 9-31 to be -6 to +4 km3/♂y, or roughly -0.039% to +0.026% of the mean atmospheric CO2 mass/♂y. The indeterminate sign results chiefly from uncertainty in the amounts of deposition or erosion on the upper surfaces of deposits (as opposed to scarp retreat). Erosion and net deposition in this period appear to be controlled by summertime planetary scale dust events, the largest occurring in MY 9, another, smaller one in MY 28. The rates of erosion and the deposition observed since MY 9 appear to be consistent with the types of deposits and erosional behavior found in most of the residual cap. However, small areas (<10%) of the cap are distinguished by their greater thickness, polygonal troughs, and embayed contacts with thinner units. These deposits may require extended periods (>100 ♂y) of depositional and/or erosional conditions different from those occurring in the period since MY 9, although these environmental differences could be subtle.

Synthesis and surface properties of polyurethane end-capped with hybrid hydrocarbon/fluorocarbon double-chain phospholipid.

PubMed

Li, Jiehua; Zhang, Yi; Yang, Jian; Tan, Hong; Li, Jianshu; Fu, Qiang

2013-05-01

To improve hemocompatibility of biomedical polyurethanes (PUs), a series of new fluorinated phospholipid end-capped polyurethanes (FPCPUs) as blending PU additives were designed and synthesized using diphenyl methane diisocyanate and 1,4-butanediol as hard segment, poly(tetramethylene glycol), polypropylene glycol, polycarbonate diols, and polyethylene glycol as soft segments, respectively, aminofunctionalized hybrid hydrocarbon/fluorocarbon double-chain phospholipid as end-capper. The bulk structures and surface properties of the obtained FPCPUs were fully characterized by (1)H NMR, Fourier transform infrared, gel permeation chromatography, X-ray photoelectron spectroscopy, differential scanning calorimetry, atomic force microscopy, and water contact angle measurement. It was found that the phosphatidylcholine groups could enrich on the surfaces and subsurfaces with the help of the fluorocarbon chains and self-assemble into mimic biomembrane on these polymer surfaces. These surfaces could effectively suppress fibrinogen adsorption, as evaluated by enzyme-linked immunosorbent assay method. Our work indicates that the FPCPUs should be one of the most potential modified additives for enhancing hemocompatibility of traditional medical PUs. Copyright © 2012 Wiley Periodicals, Inc.

Telomere fusion in Drosophila: The role of subtelomeric chromatin

PubMed Central

Marzullo, Marta; Gatti, Maurizio

2015-01-01

Drosophila telomeres are maintained by transposition to chromosome ends of the HeT-A, TART and TAHRE retrotransposons, collectively designated as HTT. Although all Drosophila telomeres terminate with HTT arrays and are capped by the terminin complex, they differ in the type of subtelomeric chromatin. The HTT sequences of YS, YL, XR, and 4L are juxtaposed to constitutive heterochromatin, while the HTTs of the other telomeres are linked to either the TAS repeat-associated chromatin (XL, 2L, 2R, 3L, 3R) or to the specialized 4R chromatin. We found that mutations in pendolino (peo) cause (telomeric fusions) that preferentially involve the heterochromatin-associated telomeres (Ha-telomeres), a telomeric fusion pattern never observed in the other 10 telomere-capping mutants characterized so far. Peo, is homologous to the E2 variant ubiquitin-conjugating enzymes and is required for DNA replication. Our analyses lead us to hypothesize that DNA replication in Peo-depleted cells results in specific fusigenic lesions concentrated in Ha-telomeres. These data provide the first demonstration that subtelomeres can affect telomere fusion. PMID:26786804

CAP - JET PROPULSION LABORATORY CONTAMINATION ANALYSIS PROGRAM

NASA Technical Reports Server (NTRS)

Millard, J. M.

1994-01-01

The Jet Propulsion Laboratory Contamination Analysis Program (CAP) is a generalized transient executive analysis computer code which solves realistic mass transport problems in the free molecular flow environment. These transport problems involve mass flux from surface source emission and re-emission, venting, and engine emission. CAP solution capability allows for one-bounce mass reflections if required. CAP was developed to solve thin-film contamination problems in the free molecular flow environment, the intent being to provide a powerful analytic tool for evaluating spacecraft contamination problems. The solution procedure uses an enclosure method based on a lumped-parameter multinodal approach with mass exchange between nodes. Transient solutions are computed by the finite difference Euler method. First-order rate theory is used to represent surface emission and reemission (user care must be taken to insure the problem is appropriate for such behavior), and all surface emission and reflections are assumed diffuse. CAP does not include the effects of post-deposition chemistry or interaction with the ambient atmosphere. CAP reads in a model represented by a multiple-block data stream. CAP allows the user to edit the input data stream and stack sequential editing operations (or cases) in order to make complex changes in behavior (surface temperatures, engine start-up and shut-down, etc.) in a single run if desired. The eight data blocks which make up the input data stream consist of problem control parameters, nodal data (area, temperature, mass, etc.), engine or vent distribution factors (based upon plume definitions), geometric configuration factors (diffuse surface emission), surface capture coefficient tables, source emission rate constant tables, reemission rate constant tables, and partial node to body collapse capability (for deposition rates only). The user must generate this data stream, since neither the problem-specific geometric relationships, the constituents involved, nor plume distribution functions are a part of CAP. Instead, these are used to generate the data stream model CAP solves. Outputs vary from individual deposition rates of exchange, on an internodal basis and on a constituent basis as a function of time, to deposition on each surface on a constituent basis as a function of time. The type of outputs may be user-specified by control parameters. CAP allows the user to select output intervals within the solution interval and to generate restart nodal data blocks. CAP is composed of several FORTRAN subroutines which serve specific functions and can be easily edited. The code is relatively small (2152 statements), and contains comment statements for all operations. It is written in relatively generic FORTRAN to be adaptable to a variety of computers. CAP was implemented on a DEC VAX 11/780 computer, and is distributed on a 9-track DEC VAX BACKUP format magnetic tape. Virtual memory required is 4.6 MB, which corresponds to a 900 node model capacity. CAP was originally developed under contract for NASA/Goddard Space Flight Center in 1979 by JPL, and was subsequently modified as required for project support at JPL. CAP is a copyrighted work with all copyright vested in NASA.

Phosphazene additives

DOEpatents

Harrup, Mason K; Rollins, Harry W

2013-11-26

An additive comprising a phosphazene compound that has at least two reactive functional groups and at least one capping functional group bonded to phosphorus atoms of the phosphazene compound. One of the at least two reactive functional groups is configured to react with cellulose and the other of the at least two reactive functional groups is configured to react with a resin, such as an amine resin of a polycarboxylic acid resin. The at least one capping functional group is selected from the group consisting of a short chain ether group, an alkoxy group, or an aryloxy group. Also disclosed are an additive-resin admixture, a method of treating a wood product, and a wood product.

Remediation System Evaluation, Douglas Road Landfill Superfund Site

EPA Pesticide Factsheets

The Douglas Road Landfill Superfund Site is located in St. Joseph County just north of Mishawaka,Indiana. The site consists of a 16-acre capped landfill located on an approximately 32-acre lot (includingthe land purchased in 1999 for a wetlands...

Enrichment of enzymatically mineralized gellan gum hydrogels with phlorotannin-rich Ecklonia cava extract Seanol(®) to endow antibacterial properties and promote mineralization.

PubMed

Douglas, Timothy E L; Dokupil, Agnieszka; Reczyńska, Katarzyna; Brackman, Gilles; Krok-Borkowicz, Malgorzata; Keppler, Julia K; Božič, Mojca; Van Der Voort, Pascal; Pietryga, Krzysztof; Samal, Sangram Keshari; Balcaen, Lieve; van den Bulcke, Jan; Van Acker, Joris; Vanhaecke, Frank; Schwarz, Karin; Coenye, Tom; Pamuła, Elżbieta

2016-08-10

Hydrogels offer several advantages as biomaterials for bone regeneration, including ease of incorporation of soluble substances such as mineralization-promoting enzymes and antibacterial agents. Mineralization with calcium phosphate (CaP) increases bioactivity, while antibacterial activity reduces the risk of infection. Here, gellan gum (GG) hydrogels were enriched with alkaline phosphatase (ALP) and/or Seanol(®), a seaweed extract rich in phlorotannins (brown algae-derived polyphenols), to induce mineralization with CaP and increase antibacterial activity, respectively. The sample groups were unmineralized hydrogels, denoted as GG, GG/ALP, GG/Seanol and GG/Seanol/ALP, and hydrogels incubated in mineralization medium (0.1 M calcium glycerophosphate), denoted as GG/ALP_min, GG/Seanol_min and GG/Seanol/ALP_min. Seanol(®) enhanced mineralization with CaP and also increased compressive modulus. Seanol(®) and ALP interacted in a non-covalent manner. Release of Seanol(®) occurred in a burst phase and was impeded by ALP-mediated mineralization. Groups GG/Seanol and GG/ALP/Seanol exhibited antibacterial activity against methicillin-resistant Staphylococcus aureus. GG/Seanol/ALP_min, but not GG/Seanol_min, retained some antibacterial activity. Eluates taken from groups GG/ALP_min, GG/Seanol_min and GG/ALP/Seanol_min displayed comparable cytotoxicity towards MG-63 osteoblast-like cells. These results suggest that enrichment of hydrogel biomaterials with phlorotannin-rich extracts is a promising strategy to increase mineralizability and antibacterial activity.

Convection and electrodynamic signatures in the vicinity of a Sun-aligned arc: Results from the Polar Acceleration Regions and Convection Study (Polar ARCS)

NASA Technical Reports Server (NTRS)

Weiss, L. A.; Weber, E. J.; Reiff, P. H.; Sharber, J. R.; Winningham, J. D.; Primdahl, F.; Mikkelsen, I. S.; Seifring, C.; Wescott, Eugene M.

1994-01-01

An experimental campaign designed to study high-latitude auroral arcs was conducted in Sondre Stromfjord, Greenland, on February 26, 1987. The Polar Acceleration Regions and Convection Study (Polar ARCS) consisted of a coordinated set of ground-based, airborne, and sounding rocket measurements of a weak, sun-aligned arc system within the duskside polar cap. A rocket-borne barium release experiment, two DMSP satellite overflights, all-sky photography, and incoherent scatter radar measurements provided information on the large-scale plasma convection over the polar cap region while a second rocket instrumented with a DC magnetometer, Langmuir and electric field probes, and an electron spectrometer provided measurements of small-scale electrodynamics. The large-scale data indicate that small, sun-aligned precipitation events formed within a region of antisunward convection between the duskside auroral oval and a large sun-aligned arc further poleward. This convection signature, used to assess the relationship of the sun-aligned arc to the large-scale magnetospheric configuration, is found to be consistent with either a model in which the arc formed on open field lines on the dusk side of a bifurcated polar cap or on closed field lines threading an expanded low-latitude boundary layer, but not a model in which the polar cap arc field lines map to an expanded plasma sheet. The antisunward convection signature may also be explained by a model in which the polar cap arc formed on long field lines recently reconnected through a highly skewed plasma sheet. The small-scale measurements indicate the rocket passed through three narrow (less than 20 km) regions of low-energy (less than 100 eV) electron precipitation in which the electric and magnetic field perturbations were well correlated. These precipitation events are shown to be associated with regions of downward Poynting flux and small-scale upward and downward field-aligned currents of 1-2 micro-A/sq m. The paired field-aligned currents are associated with velocity shears (higher and lower speed streams) embedded in the region of antisunward flow.

The effectiveness of pneumococcal polysaccharide vaccine 23 (PPV23) in the general population of 50 years of age and older: A systematic review and meta-analysis.

PubMed

Kraicer-Melamed, Hannah; O'Donnell, Shauna; Quach, Caroline

2016-03-18

Two pneumococcal vaccines currently exist and have been recommended for the prevention of pneumococcal infection in adults 65 years of age and older: the 23-valent polysaccharide (PPV23) and the conjugate 13-valent (PCV13) vaccine. To evaluate and summarize the results from all studies reporting on the vaccine effectiveness of PPV23 in preventing invasive pneumococcal disease (IPD) and community-acquired pneumonia (CAP) in individuals over the age of 50. Systematic database searches were completed in PubMed, Medline, Embase, CINAHL, Web of Science, and Cochrane. Google Scholar and hand searches of seminal articles and past systematic reviews were employed. Studies were included if they independently evaluated the effect of PPV23 on IPD and/or CAP in adults (50+). Data extraction and quality assessment were both completed independently by two researchers. Quality was assessed using the National Advisory Committee on Immunization methodology for quality assessment. All conflicts were resolved by consensus. The vaccine effectiveness for PPV23 in preventing IPD was 50% (95% CI: 21%-69%) for cohort studies and 54% (95% CI: 32%-69%) for case-control studies. The VE estimates for CAP were 4% (95% CI: -26%-26%) for trials, 17% (95% CI: -26%-45%) for cohort studies, and 7% (95% CI: -10%-21%) for case-control studies. The vaccine effectiveness of PPV23 in preventing IPD and all-cause CAP was consistent with past systematic reviews and similar to the estimates that were reported in the CAPiTA trial evaluating the vaccine effectiveness of PCV13. Consistent benefits were also reported across ecological studies and reports of surveillance data for the general population 50 years and older. The results suggests that the current practice of vaccinating the adults 65 years of age and older with PPV23 would have similar benefits to PCV13 in preventing potential cases of all-serotype IPD and all-cause CAP. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sedimentary history and mass flow structures of Chryse and Acidalia Planitiae, Mars

USGS Publications Warehouse

Tanaka, K.L.

1997-01-01

Geologic mapping and crater counting in Chryse and Acidalia Planitiae (GAP) reveal five major sedimentary deposits of Hesperian to Early Amazonian age, including (1) a mass flow deposited during the Early Hesperian near Deuteronilus Mensae (northeast of the map region) that may have resulted from the carving of Kasei Valles, >3000 km southwest of the exposed part of the deposit; (2) knobby plains material consisting of channel (likely; from Simud and Tiu Valles and possibly Ares and Shalbatana Valles) and mass-wasting deposits in central and eastern CAP; (3) material largely from Maja and Ares Valles emplaced in at least western and southern CAP (outcrops in southern Chryse Planitia developed thermokarst); (4) a thin mass flow covering much of southern Chryse Planitia that emanated from Simud and Tiu Valles; and (5) a thick, extensive (perhaps >3500 km across) mass flow deposit in central and northern CAP derived from accumulation and backflow of the preceding thin mass flow or perhaps melting of polar deposits. Other possible deposits may not be recognizable owing to burial by younger materials or a lack of morphologic signature. Various associated landforms appear to be consistent with the mass flow interpretations, including lobate and linear scarps along deposit edges, fractures related to desiccation of thick sediments, troughs, and ridges near the edges of the deposit indicative of secondary mass movement and deformation, pitted domes and fissure-fed flows possibly formed by sedimentary (mud) eruptions, and longitudinal channel grooves perhaps formed by roller vortices. No convincing evidence for paleoshorelines or stagnant ice sheets is found in CAP. These findings suggest that mass flow and hyperconcentrated flooding may have been the predominant processes of outflow-channel dissection in CAP. Elsewhere in the northern plains, similar landforms are prevalent. The mass flow interpretation does not require either multiple episodes of extraordinarily high water-discharge rates achieved by freeing huge volumes of water from the crust, repetitive recycling of immense volumes of water into highland aquifers at the heads of Chryse channels, or profound climate change. Mars Pathfinder will most likely land on and inspect the surface of the thin mass flow that originated from the canyons of Simud and Tiu Valles.

Erosion patterns produced by the paleo Haizishan ice cap, SE Tibetan Plateau

NASA Astrophysics Data System (ADS)

Fu, P.; Stroeven, A. P.; Harbor, J.; Hättestrand, C.; Heyman, J.; Caffee, M. W.

2017-12-01

Erosion is a primary driver of landscape evolution, topographic relief production, geochemical cycles, and climate change. Combining in situ 10Be and 26Al exposure age dating, geomorphological mapping, and field investigations, we examine glacial erosion patterns of the almost 4,000 km2 paleo Haizishan ice cap on the southeastern Tibetan Plateau. Our results show that ice caps on the low relief Haizishan Plateau produced a zonal pattern of landscape modification. In locations where apparent exposure ages on bedrock are consistent with the last deglaciation, complete resetting of the cosmogenic exposure age clock indicates glacial erosion of at least a few meters. However, older apparent exposure ages on bedrock in areas known to have been covered by the paleo ice cap during the Last Glacial Maximum indicate inheritance and thus limited glacial erosion. Inferred surface exposure ages from cosmogenic depth profiles through two saprolites vary from resetting and thus saprolite profile truncation to nuclide inheritance indicating limited erosion. Finally, significant nuclide inheritance in river sand samples from basins on the scoured plateau surface also indicate limited glacial erosion during the last glaciation. Hence, for the first time, our study shows clear evidence of preservation under non-erosive ice on the Tibetan Plateau. As patterns of glacial erosion intensity are largely driven by the basal thermal regime, our results confirm earlier inferences from geomorphology for a concentric basal thermal pattern for the paleo Haizishan ice cap during the LGM.

Detection of Anomalous Noise Events on Low-Capacity Acoustic Nodes for Dynamic Road Traffic Noise Mapping within an Hybrid WASN

PubMed Central

2018-01-01

One of the main aspects affecting the quality of life of people living in urban and suburban areas is the continuous exposure to high road traffic noise (RTN) levels. Nowadays, thanks to Wireless Acoustic Sensor Networks (WASN) noise in Smart Cities has started to be automatically mapped. To obtain a reliable picture of the RTN, those anomalous noise events (ANE) unrelated to road traffic (sirens, horns, people, etc.) should be removed from the noise map computation by means of an Anomalous Noise Event Detector (ANED). In Hybrid WASNs, with master-slave architecture, ANED should be implemented in both high-capacity (Hi-Cap) and low-capacity (Lo-Cap) sensors, following the same principle to obtain consistent results. This work presents an ANED version to run in real-time on μController-based Lo-Cap sensors of a hybrid WASN, discriminating RTN from ANE through their Mel-based spectral energy differences. The experiments, considering 9 h and 8 min of real-life acoustic data from both urban and suburban environments, show the feasibility of the proposal both in terms of computational load and in classification accuracy. Specifically, the ANED Lo-Cap requires around 16 of the computational load of the ANED Hi-Cap, while classification accuracies are slightly lower (around 10%). However, preliminary analyses show that these results could be improved in around 4% in the future by means of considering optimal frequency selection. PMID:29677147

Long term management of patients with cryopyrin-associated periodic syndromes (CAPS): focus on rilonacept (IL-1 Trap).

PubMed

Church, Leigh D; Savic, Sinisa; McDermott, Michael F

2008-12-01

Cryopyrin-associated periodic syndromes (CAPS) are a group of inherited inflammatory disorders consisting of familial cold-induced autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID; also known as chronic infantile neurologic, cutaneous, articular [CINCA] syndrome). These rare disorders are associated with heterozygous mutations in the NLRP3 (CIAS1) gene, which encodes the protein NALP3 or cryopyrin, and inflammation driven by excessive production of the cytokine interleukin-1beta (IL-1beta). Amyloidosis is a serious complication with 25% of MWS patients developing amyloidosis, with occasional fatal consequences, whilst up to 20% of CINCA/NOMID patients die from various complications, before reaching the early adulthood. In some CINCA/NOMID adult survivors amyloidosis can also occur. Prior to the discovery of the CIAS1 gene mutations and the advent of IL-1 targeted therapy, treatment was aimed at suppressing inflammation, with limited success. The selective blockade of IL-1beta, with anakinra (IL-1 receptor antagonist), not only provided supportive evidence for the role of IL-1beta in CAPS, but also demonstrated the efficacy of targeting IL-1beta for treatment of these conditions. In February, 2008, 'Orphan Drug' approval from the Food and Drug Administration (FDA) for rilonacept (IL-1 Trap/Arcalyst(), Regeneron Pharmaceuticals, Inc) was given for the treatment of two CAPS disorders, FCAS and MWS in adults and children 12 years and older, making rilonacept the first therapy approved for the treatment of CAPS.

Detection of Anomalous Noise Events on Low-Capacity Acoustic Nodes for Dynamic Road Traffic Noise Mapping within an Hybrid WASN.

PubMed

Alsina-Pagès, Rosa Ma; Alías, Francesc; Socoró, Joan Claudi; Orga, Ferran

2018-04-20

One of the main aspects affecting the quality of life of people living in urban and suburban areas is the continuous exposure to high road traffic noise (RTN) levels. Nowadays, thanks to Wireless Acoustic Sensor Networks (WASN) noise in Smart Cities has started to be automatically mapped. To obtain a reliable picture of the RTN, those anomalous noise events (ANE) unrelated to road traffic (sirens, horns, people, etc.) should be removed from the noise map computation by means of an Anomalous Noise Event Detector (ANED). In Hybrid WASNs, with master-slave architecture, ANED should be implemented in both high-capacity (Hi-Cap) and low-capacity (Lo-Cap) sensors, following the same principle to obtain consistent results. This work presents an ANED version to run in real-time on μ Controller-based Lo-Cap sensors of a hybrid WASN, discriminating RTN from ANE through their Mel-based spectral energy differences. The experiments, considering 9 h and 8 min of real-life acoustic data from both urban and suburban environments, show the feasibility of the proposal both in terms of computational load and in classification accuracy. Specifically, the ANED Lo-Cap requires around 1 6 of the computational load of the ANED Hi-Cap, while classification accuracies are slightly lower (around 10%). However, preliminary analyses show that these results could be improved in around 4% in the future by means of considering optimal frequency selection.

Rates of Deglaciation during the Last Glaciation and Holocene in the Cordillera Vilcanota-Quelccaya Ice Cap Region, Southeastern Perú

NASA Astrophysics Data System (ADS)

Mark, Bryan G.; Seltzer, Geoffrey O.; Rodbell, Donald T.; Goodman, Adam Y.

2002-05-01

Moraine chronology is combined with digital topography to model deglacial rates of paleoglacier volumes in both the Huancané Valley on the west side of the Quelccaya Ice Cap and the Upismayo Valley on the northwest side of the Cordillera Vilcanota. The fastest rates of deglaciation (39×10 -5 to 114×10 -5 km 3 yr -1 and 112×10 -5 to 247×10 -5 km 3 yr -1 for each valley, respectively) were calculated for the most recent paleoglaciers, corresponding to the last few centuries. These results are consistent with observations in the Venezuelan Andes showing high rates of deglaciation since the Little Ice Age. These rates also fall within the range of 20th century rates of deglaciation measured on the Quelccaya Ice Cap (29×10 -5 to 220×10 -5 km 3 yr -1, Brecher and Thompson, 1993; Thompson, 2000). These results imply that rates of deglaciation may fluctuate significantly over time and that high rates of deglaciation may not be exclusive to the late 20th century. Equilibrium line altitude (ELA) depressions for the ice volumes of the last glaciation modeled here were computed as 230 m for the Quelccaya Ice Cap and 170 m for the Cordillera Vilcanota. Maximum ELA depressions are lower than previously published: <500 m for the Cordillera Vilcanota and <400 m for the Quelccaya Ice Cap. These lower values could imply a topographic control over paleoglacier extent.

Water-Solubilized, Cap-Stabilized, Helical Polyalanines: Calibration Standards for NMR and CD Analyses

PubMed Central

Heitmann, Björn; Job, Gabriel E.; Kennedy, Robert J.; Walker, Sharon M.; Kemp, Daniel S.

2006-01-01

NMR and CD studies are reported for two length series of solubilized, spaced, highly helical polyalanines that are N-capped by the optimal helix stabilizer βAsp-Hel and C-capped by β-aminoalanine beta and that are studied in water at 2 °C, pH 1–8. NMR analysis yields a structural characterization of the peptide AcβAspHelAla8betaNH2 and selected members of one βAspHelAlanbeta series. At pH > 4.5 the βAspHel cap provides a preorganized triad of carboxylate anion and two amide residues that is complementary to the helical polyalanine N-terminus. The C-terminal β-aminoalanine assumes a helix-stabilizing conformation consistent with literature precedents. H(N)CO NMR experiments applied to capped, uniformly 13C- and 15N-labeled Ala8 and Ala12 peptides define Alan hydrogen bonding signatures as α-helical without detectable 310 character. Relative NH→ND exchange rates yield site protection factors PFi that define uniquely high fractional helicities FH for the peptide Alan regions. These Alan calibration series, studied in water and lacking helix-stabilizing tertiary structure, yield the first 13C NMR chemical shifts, 3JHNHα coupling constants, and CD ellipticities [θMolar]λ,n characteristic of a fully helical alanine within an Alan context. CD data are used to assign parameters X and [θ]λ,∞, required for rigorous calculation of FH values from CD ellipticities. PMID:15701003

Disaccharidase Deficiencies in Children With Chronic Abdominal Pain.

PubMed

El-Chammas, Khalil; Williams, Sara E; Miranda, Adrian

2017-03-01

Carbohydrate intolerance or malabsorption has been suggested as a cause of chronic abdominal pain (CAP) in a subset of patients. We aimed to evaluate disaccharidase deficiencies in children with functional CAP and to correlate deficiencies with clinical features. Patients presenting to the gastroenterology clinic at Children's Hospital of Wisconsin with abdominal pain prospectively completed a detailed demographic, history, and symptom questionnaire. The CAP cohort included those with at least 1 month of symptoms. Data on disaccharidase activity and histology of endoscopic biopsies were collected retrospectively. Only patients with normal histology were included in the study. The association between groups with low disaccharidases and clinical features was examined. A total of 203 pediatric patients with CAP were included. The mean (SD) age was 11.5 (3.1) years, and 32.5% were male. The percentages of abnormally low disaccharidase levels using the standard laboratory cutoffs were lactase, 37%; sucrase, 21%; glucoamylase, 25%; and palatinase, 8%. Thirty-nine percent of the patients with low lactase also had low sucrase, and 67% of the patients with low sucrase had low lactase. There was no significant difference in the activities of any of the disaccharidases or sucrase/lactase ratio in relation to age. Also, no association was found between stool consistency, stool frequency, or location of pain and low disaccharidase activity. A large proportion of patients with CAP have deficiencies in disaccharidases. Bowel frequency, vomiting, or location of pain was no different between groups, suggesting that these clinical features cannot be used to predict disaccharidase deficiencies.

Case studies of of the oxidation of sulphur dioxide in a hill cap cloud using ground and aircraft based measurements

NASA Astrophysics Data System (ADS)

Gallagher, M. W.; Downer, R. M.; Choularton, T. W.; Gay, M. J.; Stromberg, I.; Mill, C. S.; Radojevic, M.; Tyler, B. J.; Bandy, B. J.; Penkett, S. A.; Davies, T. J.; Dollard, G. J.; Jones, B. M. R.

1990-10-01

Two case studies are presented which investigate the aqueous phase oxidation of sulfur dioxide (SO2) within a cap cloud on the summit of Great Dun Fell (847 m above sea level) in England. Data gathered by aircraft showed that hydrogen peroxide (H2O2) concentrations in the free troposphere were much greater than near the ground and that entrainment of air containing H2O2, into the cap cloud could provide a significant supply of oxidant. These findings suggest that the entrainment of H2O2 into cloud systems may be important to the oxidation of SO2, particularly in the absence of large concentrations of ammonia gas, which may favor oxidation by ozone. It is also shown that the apparent reaction rate of H2O2 within the cloud is consistent with our previous estimates made and were substantially larger than would be predicted from laboratory studies in bulk solutions (Chandler et al., 1988b). Sulphate, (SO42-), production was observed when significant concentrations of SO2 were present. The measured concentrations of the principal species involved in one of the case studies were consistent with model predictions which take account of SO2 oxidation by H2O2 and O3 and an enhanced H2O2-SO2 reaction rate.

A thermolabile aspartic proteinase from Mucor mucedo DSM 809: gene identification, cloning, and functional expression in Pichia pastoris.

PubMed

Yegin, Sirma; Fernandez-Lahore, Marcelo

2013-06-01

In this study, the cDNA encoding the aspartic proteinase of Mucor mucedo DSM 809 has been identified by RNA ligased-mediated and oligo-capping rapid amplification of cDNA ends (RACE) technique. The gene contained an open reading frame of 1,200 bp and encoded for a signal peptide of 21 amino acid residues. Two N-glycosylation sites were observed within the identified sequence. The proteinase gene was cloned into the vector pGAPZαA and expressed in Pichia pastoris X-33 for the first time. The protein has been secreted in functionally active form into the culture medium. The expression system does not require any acid activation process. The factors affecting the expression level were optimized in shaking flask cultures. Maximum enzyme production was observed with an initial medium pH of 3.5 at 20 °C and 220 rpm shaking speed utilizing 4 % glucose as a carbon and energy source. The enzyme was purified with cation exchange chromatography and further studies revealed that the enzyme was secreted in glycosylated form. The purified enzyme exhibited remarkable sensitivity to thermal treatment and became completely inactivated after incubation at 55 °C for 10 min. These results indicated that the recombinant proteinase could be considered as a potential rennet candidate for the cheese-making industry.

A disulfide-stabilized conformer of methionine synthase reveals an unexpected role for the histidine ligand of the cobalamin cofactor

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

Datta, Supratim; Koutmos, Markos; Pattridge, Katherine A.

2008-07-08

B{sub 12}-dependent methionine synthase (MetH) from Escherichia coli is a large modular protein that is alternately methylated by methyltetrahydrofolate to form methylcobalamin and demethylated by homocysteine to form cob(I)alamin. Major domain rearrangements are required to allow cobalamin to react with three different substrates: homocysteine, methyltetrahydrofolate, and S-adenosyl-l-methionine (AdoMet). These same rearrangements appear to preclude crystallization of the wild-type enzyme. Disulfide cross-linking was used to lock a C-terminal fragment of the enzyme into a unique conformation. Cysteine point mutations were introduced at Ile-690 and Gly-743. These cysteine residues span the cap and the cobalamin-binding module and form a cross-link that reducesmore » the conformational space accessed by the enzyme, facilitating protein crystallization. Here, we describe an x-ray structure of the mutant fragment in the reactivation conformation; this conformation enables the transfer of a methyl group from AdoMet to the cobalamin cofactor. In the structure, the axial ligand to the cobalamin, His-759, dissociates from the cobalamin and forms intermodular contacts with residues in the AdoMet-binding module. This unanticipated intermodular interaction is expected to play a major role in controlling the distribution of conformers required for the catalytic and the reactivation cycles of the enzyme.« less

18-gauge needle cap as adjunct to prevent kinking of endotracheal tube.

PubMed

Chan, Fuan Chiang; Kawamoto, Henry K; Bradley, James P

2012-11-01

A self-retaining Dingman mouth retractor is widely used to keep the mouth open during cleft palate and intraoral surgery. The airway is at risk of being crushed or occluded as the gag (tongue plate) of the Dingman mouth retractor is being pushed against the endotracheal tube.Kinking of the endotracheal tube between the teeth and Dingman mouth retractor has been reported even with the oral Ring-Adair-Elwyn or flexometallic or armored endotracheal tubes. To minimize kinking of the endotracheal tube and its consequent complications, we routinely insert an 18-gauge needle cap at the potential space between the teeth and the tongue plate (gag) of the Dingman mouth retractor, which is situated lateral to the endotracheal tube. In our experience of approximately 5000 intraoral cases using a Dingman mouth retractor and 18-gauge needle cap, we have not had any tooth avulsion or aspiration of the 18-gauge foreign body while maintaining a consistent and secured airway during cleft palate and intraoral surgery.

Field performance of a geosynthetic clay liner landfill capping system under simulated waste subsidence

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

Weiss, W.; Siegmund, M.; Alexiew, D.

1995-10-01

A flexible landfill capping system consisting of a 3-D-geocore composite for gas vent, a Geosynthetic Clay Liner (GCL) for sealing and a 3-D-geocore composite for drainage of the vegetation soil was built on a test field at Michelshoehe landfill near Weimar, Germany. At four locations airbags were installed underneath the thin capping system to simulate subsidences. On top of three of these airbags overlaps of the GCL were positioned, for comparison there was no overlap at the fourth location. After hydratation of the GCL the airbags were de-aerated and subsidences occurred with app. 5 % tensile strain in the GCL.more » For three weeks the test field was intensively sprinkled in intervals. Then horizontal and vertical deformations were measured, but not displacements were registered in the overlaps. The evaluation of the GCL`s permeability showed no significant difference between the locations with and without overlaps.« less

Experimental investigation of gas flow rate and electric field effect on refractive index and electron density distribution of cold atmospheric pressure-plasma by optical method, Moiré deflectometry

NASA Astrophysics Data System (ADS)

Khanzadeh, Mohammad; Jamal, Fatemeh; Shariat, Mahdi

2018-04-01

Nowadays, cold atmospheric-pressure (CAP) helium plasma jets are widely used in material processing devices in various industries. Researchers often use indirect and spectrometric methods for measuring the plasma parameters which are very expensive. In this paper, for the first time, characterization of CAP, i.e., finding its parameters such as refractive index and electron density distribution, was carried out using an optical method, Moiré deflectometry. This method is a wave front analysis technique based on geometric optics. The advantages of this method are simplicity, high accuracy, and low cost along with the non-contact, non-destructive, and direct measurement of CAP parameters. This method demonstrates that as the helium gas flow rate decreases, the refractive index increases. Also, we must note that the refractive index is larger in the gas flow consisting of different flow rates of plasma comparing with the gas flow without the plasma.

Electromagnetically induced reflectance and Fano resonance in one dimensional superconducting photonic crystal

NASA Astrophysics Data System (ADS)

Athe, Pratik; Srivastava, Sanjay; Thapa, Khem B.

2018-04-01

In the present work, we demonstrate the generation of optical Fano resonance and electromagnetically induced reflectance (EIR) in one-dimensional superconducting photonic crystal (1D SPC) by numerical simulation using transfer matrix method as analysis tool. We investigated the optical response of 1D SPC structure consisting of alternate layer of two different superconductors and observed that the optical spectra of this structure exhibit two narrow reflectance peaks with zero reflectivity of sidebands. Further, we added a dielectric cap layer to this 1D SPC structure and found that addition of dielectric cap layer transforms the line shape of sidebands around the narrow reflectance peaks which leads to the formation of Fano resonance and EIR line shape in reflectance spectra. We also studied the effects of the number of periods, refractive index and thickness of dielectric cap layer on the lineshape of EIR and Fano resonances. It was observed that the amplitude of peak reflectance of EIR achieves 100% reflectance by increasing the number of periods.

ARC-1989-AC89-7046

NASA Image and Video Library

1989-08-25

P-34764 Voyager 2 obtained this high resolution color image of Neptune's large satellite Triton during its close flyby. Approximately a dozen individual images were combined to produce this comprehensive view of the Neptune-facing hemisphere of Triton. Fine detail is provided by high resolution, clear-filter images, with color information added from lower resolution frames. The large south polar cap at the bottom of the image is highly refective and slightly pink in color , and may consist of a slowly evaporating layer of nitrogen ice deposited during the previous winter. From the ragged edge of the polar cap northward the satellite's face is generously darker and redder in color. This coloring may be produced by the action of ultraviolet light and magnetospheric radiation upon methane in the atmosphere and surface. Running across this darker region , approximately parallel to the edge of the polar cap, is a band of brighter white material that is almost bluish in color. The underlying topography in this bright band is similiar, however to that in the darker, redder regions surrounding it.

Shuttle Entry Air Data System (SEADS) hardware development. Volume 1: Summary

NASA Technical Reports Server (NTRS)

While, D. M.

1983-01-01

Hardware development of the Shuttle Entry Data System (SEADS) is described. The system consists of an array of fourteen pressure ports, installed in an Orbiter nose cap, which, when coupled with existing fuselage mounted static pressure ports permits computation of entry flight parameters. Elements of the system that are described include the following: (1) penetration assemblies to place pressure port openings at the surface of the nose cap; (2) pressure tubes to transmit the surface pressure to transducers; (3) support posts or manifolds to provide support for, and reduce the length of, the individual pressure tubes; (4) insulation for the manifolds; and (5) a SEADS nose cap. Design, analyses, and tests to develop and certify design for flight are described. Specific tests include plasma arc exposure, radiant thermal, vibration, and structural. Volume one summarizes highlights of the program, particularly as they relate to the final design of SEADS. Volume two summarizes all of the Vought responsible activities in essentially a chronological order.

Mars south polar spring and summer temperatures - A residual CO2 frost

NASA Technical Reports Server (NTRS)

Kieffer, H. H.

1979-01-01

Viking infrared thermal mapper (IRTM) energy measurements over the Mars south polar cap throughout the Martian spring and summer revealed complex spatial, spectral, and temporal variations. High albedos did not directly correspond with low temperatures, and as the cap shrank to its residual position, it maintained large differences in brightness temperature between the four IRTM surface-sensing bands at 7, 9, 11, and 20 microns. The late summer infrared spectral pattern can be matched by a surface consisting of CO2 frost with 20 micron emissivity of 0.8 and about 6% dark, warm soil under a dusty atmosphere of moderate infrared opacity and spectral properties similar to those measured for the Martian global dust storms. Low temperature, the absence of appreciable water vapor in the south polar atmosphere, and the absence of surface warming expected if H2O were to become exposed, all imply that the residual south polar cap was covered by solid CO2.

Shuttle Entry Air Data System (SEADS) hardware development. Volume 2: History

NASA Technical Reports Server (NTRS)

While, D. M.

1983-01-01

Hardware development of the Shuttle Entry Air Data System (SEADS) is described. The system consists of an array of fourteen pressure ports, installed in an Orbiter nose cap, which, when coupled with existing fuselage mounted static pressure ports permits computation of entry flight parameters. Elements of the system that are described include the following: (1) penetration assemblies to place pressure port openings at the surface of the nose cap; (2) pressure tubes to transmit the surface pressure to transducers; (3) support posts or manifolds to provide support for, and reduce the length of, the individual pressure tubes; (4) insulation for the manifolds; and (5) a SEADS nose cap. Design, analyses, and tests to develop and certify design for flight are described. Specific tests included plasma arc exposure, radiant thermal, vibration, and structural. Volume one summarizes highlights of the program, particularly as they relate to the final design of SEADS. Volume two summarizes all of the Vought responsible activities in essentially a chronological order.

A spatial characterization of the Sagittarius dwarf galaxy tidal tails

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

Newby, Matthew; Cole, Nathan; Newberg, Heidi Jo

2013-06-01

We measure the spatial density of F turnoff stars in the Sagittarius dwarf tidal stream, from Sloan Digital Sky Survey data, using statistical photometric parallax. We find a set of continuous, consistent parameters that describe the leading Sgr stream's position, direction, and width for 15 stripes in the north Galactic cap, and three stripes in the south Galactic cap. We produce a catalog of stars that has the density characteristics of the dominant leading Sgr tidal stream that can be compared with simulations. We find that the width of the leading (north) tidal tail is consistent with recent triaxial andmore » axisymmetric halo model simulations. The density along the stream is roughly consistent with common disruption models in the north, but possibly not in the south. We explore the possibility that one or more of the dominant Sgr streams has been misidentified, and that one or more of the ''bifurcated'' pieces is the real Sgr tidal tail, but we do not reach definite conclusions. If two dwarf progenitors are assumed, fits to the planes of the dominant and ''bifurcated'' tidal tails favor an association of the Sgr dwarf spheroidal galaxy with the dominant southern stream and the ''bifurcated'' stream in the north. In the north Galactic cap, the best fit Hernquist density profile for the smooth component of the stellar halo is oblate, with a flattening parameter q = 0.53, and a scale length of r {sub 0} = 6.73. The southern data for both the tidal debris and the smooth component of the stellar halo do not match the model fits to the north, although the stellar halo is still overwhelmingly oblate. Finally, we verify that we can reproduce the parameter fits on the asynchronous MilkyWay@home volunteer computing platform.« less

21 CFR 173.110 - Amyloglucosidase derived from Rhizopus niveus.

Code of Federal Regulations, 2013 CFR

2013-04-01

... FOOD FOR HUMAN CONSUMPTION Enzyme Preparations and Microorganisms § 173.110 Amyloglucosidase derived from Rhizopus niveus. Amyloglucosidase enzyme product, consisting of enzyme derived from Rhizopus... in man or other animals. (c) The enzyme is produced by a process which completely removes the...

21 CFR 173.110 - Amyloglucosidase derived from Rhizopus niveus.

Code of Federal Regulations, 2012 CFR

2012-04-01

... FOOD FOR HUMAN CONSUMPTION Enzyme Preparations and Microorganisms § 173.110 Amyloglucosidase derived from Rhizopus niveus. Amyloglucosidase enzyme product, consisting of enzyme derived from Rhizopus... in man or other animals. (c) The enzyme is produced by a process which completely removes the...

21 CFR 173.110 - Amyloglucosidase derived from Rhizopus niveus.

Code of Federal Regulations, 2011 CFR

2011-04-01

... FOOD FOR HUMAN CONSUMPTION Enzyme Preparations and Microorganisms § 173.110 Amyloglucosidase derived from Rhizopus niveus. Amyloglucosidase enzyme product, consisting of enzyme derived from Rhizopus... in man or other animals. (c) The enzyme is produced by a process which completely removes the...

21 CFR 173.110 - Amyloglucosidase derived from Rhizopus niveus.

Code of Federal Regulations, 2010 CFR

2010-04-01

... FOOD FOR HUMAN CONSUMPTION Enzyme Preparations and Microorganisms § 173.110 Amyloglucosidase derived from Rhizopus niveus. Amyloglucosidase enzyme product, consisting of enzyme derived from Rhizopus... in man or other animals. (c) The enzyme is produced by a process which completely removes the...

Surface elevation change on ice caps in the Qaanaaq region, northwestern Greenland

NASA Astrophysics Data System (ADS)

Saito, Jun; Sugiyama, Shin; Tsutaki, Shun; Sawagaki, Takanobu

2016-09-01

A large number of glaciers and ice caps (GICs) are distributed along the Greenland coast, physically separated from the ice sheet. The total area of these GICs accounts for 5% of Greenland's ice cover. Melt water input from the GICs to the ocean substantially contributed to sea-level rise over the last century. Here, we report surface elevation changes of six ice caps near Qaanaaq (77°28‧N, 69°13‧W) in northwestern Greenland based on photogrammetric analysis of stereo pair satellite images. We processed the images with a digital map plotting instrument to generate digital elevation models (DEMs) in 2006 and 2010 with a grid resolution of 500 m. Generated DEMs were compared to measure surface elevation changes between 2006 and 2010. Over the study area of the six ice caps, covering 1215 km2, the mean rate of elevation change was -1.1 ± 0.1 m a-1. This rate is significantly greater than that previously reported for the 2003-2008 period (-0.6 ± 0.1 m a-1) for GICs all of northwestern Greenland. This increased mass loss is consistent with the rise in summer temperatures in this region at a rate of 0.12 °C a-1 for the 1997-2013 period.

Antifungal activity of fused Mannich ketones triggers an oxidative stress response and is Cap1-dependent in Candida albicans.

PubMed

Rossignol, Tristan; Kocsis, Béla; Bouquet, Orsolya; Kustos, Ildikó; Kilár, Ferenc; Nyul, Adrien; Jakus, Péter B; Rajbhandari, Kshitij; Prókai, László; d'Enfert, Christophe; Lóránd, Tamás

2013-01-01

We investigated the antifungal activity of fused Mannich ketone (FMK) congeners and two of their aminoalcohol derivatives. In particular, FMKs with five-membered saturated rings were shown to have minimum inhibitory concentration (MIC90s) ranging from 0.8 to 6 µg/mL toward C. albicans and the closely related C. parapsilosis and C. krusei while having reduced efficacy toward C. glabrata and almost no efficacy against Aspergillus sp. Transcript profiling of C. albicans cells exposed for 30 or 60 min to 2-(morpholinomethyl)-1-indanone, a representative FMK with a five-membered saturated ring, revealed a transcriptional response typical of oxidative stress and similar to that of a C. albicans Cap1 transcriptional activator. Consistently, C. albicans lacking the CAP1 gene was hypersensitive to this FMK, while C. albicans strains overexpressing CAP1 had decreased sensitivity to 2-(morpholinomethyl)-1-indanone. Quantitative structure-activity relationship studies revealed a correlation of antifungal potency and the energy of the lowest unoccupied molecular orbital of FMKs and unsaturated Mannich ketones thereby implicating redox cycling-mediated oxidative stress as a mechanism of action. This conclusion was further supported by the loss of antifungal activity upon conversion of representative FMKs to aminoalcohols that were unable to participate in redox cycles.

Chemical Genetic Analysis and Functional Characterization of Staphylococcal Wall Teichoic Acid 2-Epimerases Reveals Unconventional Antibiotic Drug Targets.

PubMed

Mann, Paul A; Müller, Anna; Wolff, Kerstin A; Fischmann, Thierry; Wang, Hao; Reed, Patricia; Hou, Yan; Li, Wenjin; Müller, Christa E; Xiao, Jianying; Murgolo, Nicholas; Sher, Xinwei; Mayhood, Todd; Sheth, Payal R; Mirza, Asra; Labroli, Marc; Xiao, Li; McCoy, Mark; Gill, Charles J; Pinho, Mariana G; Schneider, Tanja; Roemer, Terry

2016-05-01

Here we describe a chemical biology strategy performed in Staphylococcus aureus and Staphylococcus epidermidis to identify MnaA, a 2-epimerase that we demonstrate interconverts UDP-GlcNAc and UDP-ManNAc to modulate substrate levels of TarO and TarA wall teichoic acid (WTA) biosynthesis enzymes. Genetic inactivation of mnaA results in complete loss of WTA and dramatic in vitro β-lactam hypersensitivity in methicillin-resistant S. aureus (MRSA) and S. epidermidis (MRSE). Likewise, the β-lactam antibiotic imipenem exhibits restored bactericidal activity against mnaA mutants in vitro and concomitant efficacy against 2-epimerase defective strains in a mouse thigh model of MRSA and MRSE infection. Interestingly, whereas MnaA serves as the sole 2-epimerase required for WTA biosynthesis in S. epidermidis, MnaA and Cap5P provide compensatory WTA functional roles in S. aureus. We also demonstrate that MnaA and other enzymes of WTA biosynthesis are required for biofilm formation in MRSA and MRSE. We further determine the 1.9Å crystal structure of S. aureus MnaA and identify critical residues for enzymatic dimerization, stability, and substrate binding. Finally, the natural product antibiotic tunicamycin is shown to physically bind MnaA and Cap5P and inhibit 2-epimerase activity, demonstrating that it inhibits a previously unanticipated step in WTA biosynthesis. In summary, MnaA serves as a new Staphylococcal antibiotic target with cognate inhibitors predicted to possess dual therapeutic benefit: as combination agents to restore β-lactam efficacy against MRSA and MRSE and as non-bioactive prophylactic agents to prevent Staphylococcal biofilm formation.

Chemical Genetic Analysis and Functional Characterization of Staphylococcal Wall Teichoic Acid 2-Epimerases Reveals Unconventional Antibiotic Drug Targets

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

Mann, Paul A.; Müller, Anna; Wolff, Kerstin A.

Here we describe a chemical biology strategy performed in Staphylococcus aureus and Staphylococcus epidermidis to identify MnaA, a 2-epimerase that we demonstrate interconverts UDP-GlcNAc and UDP-ManNAc to modulate substrate levels of TarO and TarA wall teichoic acid (WTA) biosynthesis enzymes. Genetic inactivation of mnaA results in complete loss of WTA and dramatic in vitro β-lactam hypersensitivity in methicillin-resistant S. aureus (MRSA) and S. epidermidis (MRSE). Likewise, the β-lactam antibiotic imipenem exhibits restored bactericidal activity against mnaA mutants in vitro and concomitant efficacy against 2-epimerase defective strains in a mouse thigh model of MRSA and MRSE infection. Interestingly, whereas MnaA servesmore » as the sole 2-epimerase required for WTA biosynthesis in S. epidermidis, MnaA and Cap5P provide compensatory WTA functional roles in S. aureus. We also demonstrate that MnaA and other enzymes of WTA biosynthesis are required for biofilm formation in MRSA and MRSE. We further determine the 1.9Å crystal structure of S. aureus MnaA and identify critical residues for enzymatic dimerization, stability, and substrate binding. Finally, the natural product antibiotic tunicamycin is shown to physically bind MnaA and Cap5P and inhibit 2-epimerase activity, demonstrating that it inhibits a previously unanticipated step in WTA biosynthesis. In summary, MnaA serves as a new Staphylococcal antibiotic target with cognate inhibitors predicted to possess dual therapeutic benefit: as combination agents to restore β-lactam efficacy against MRSA and MRSE and as non-bioactive prophylactic agents to prevent Staphylococcal biofilm formation.« less

Structural Determinants of Substrate Recognition in the HAD Superfamily Member D-glycero-D-manno-Heptose-1,7-bisphosphate Phosphatase (GmhB)

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

Nguyen, H.; Wang, L; Huang, H

2010-01-01

The haloalkanoic acid dehalogenase (HAD) enzyme superfamily is the largest family of phosphohydrolases. In HAD members, the structural elements that provide the binding interactions that support substrate specificity are separated from those that orchestrate catalysis. For most HAD phosphatases, a cap domain functions in substrate recognition. However, for the HAD phosphatases that lack a cap domain, an alternate strategy for substrate selection must be operative. One such HAD phosphatase, GmhB of the HisB subfamily, was selected for structure-function analysis. Herein, the X-ray crystallographic structures of Escherichia coli GmhB in the apo form (1.6 {angstrom} resolution), in a complex with Mg{supmore » 2+} and orthophosphate (1.8 {angstrom} resolution), and in a complex with Mg{sup 2+} and D-glycero-D-manno-heptose 1{beta},7-bisphosphate (2.2 {angstrom} resolution) were determined, in addition to the structure of Bordetella bronchiseptica GmhB bound to Mg{sup 2+} and orthophosphate (1.7 {angstrom} resolution). The structures show that in place of a cap domain, the GmhB catalytic site is elaborated by three peptide inserts or loops that pack to form a concave, semicircular surface around the substrate leaving group. Structure-guided kinetic analysis of site-directed mutants was conducted in parallel with a bioinformatics study of sequence diversification within the HisB subfamily to identify loop residues that serve as substrate recognition elements and that distinguish GmhB from its subfamily counterpart, the histidinol-phosphate phosphatase domain of HisB. We show that GmhB and the histidinol-phosphate phosphatase domain use the same design of three substrate recognition loops inserted into the cap domain yet, through selective residue usage on the loops, have achieved unique substrate specificity and thus novel biochemical function.« less

Proline Scanning Mutagenesis Reveals a Role for the Flap Endonuclease-1 Helical Cap in Substrate Unpairing*

PubMed Central

Patel, Nikesh; Exell, Jack C.; Jardine, Emma; Ombler, Ben; Finger, L. David; Ciani, Barbara; Grasby, Jane A.

2013-01-01

The prototypical 5′-nuclease, flap endonuclease-1 (FEN1), catalyzes the essential removal of single-stranded flaps during DNA replication and repair. FEN1 hydrolyzes a specific phosphodiester bond one nucleotide into double-stranded DNA. This specificity arises from double nucleotide unpairing that places the scissile phosphate diester on active site divalent metal ions. Also related to FEN1 specificity is the helical arch, through which 5′-flaps, but not continuous DNAs, can thread. The arch contains basic residues (Lys-93 and Arg-100 in human FEN1 (hFEN1)) that are conserved by all 5′-nucleases and a cap region only present in enzymes that process DNAs with 5′ termini. Proline mutations (L97P, L111P, L130P) were introduced into the hFEN1 helical arch. Each mutation was severely detrimental to reaction. However, all proteins were at least as stable as wild-type (WT) hFEN1 and bound substrate with comparable affinity. Moreover, all mutants produced complexes with 5′-biotinylated substrate that, when captured with streptavidin, were resistant to challenge with competitor DNA. Removal of both conserved basic residues (K93A/R100A) was no more detrimental to reaction than the single mutation R100A, but much less severe than L97P. The ability of protein-Ca2+ to rearrange 2-aminopurine-containing substrates was monitored by low energy CD. Although L97P and K93A/R100A retained the ability to unpair substrates, the cap mutants L111P and L130P did not. Taken together, these data challenge current assumptions related to 5′-nuclease family mechanism. Conserved basic amino acids are not required for double nucleotide unpairing and appear to act cooperatively, whereas the helical cap plays an unexpected role in hFEN1-substrate rearrangement. PMID:24126913

CONCENTRATED AMBIENT PARTICULATES (CAPS) STUDIES TO ADDRESS SOURCE-ATTRIBUTED EFFECTS ON CARDIOPULMONARY FUNCTION

EPA Science Inventory

Studies of ambient particulate matter (PM) in several venues around the world have shown consistent health impacts vis-a-vis mortality and morbidity. However, recent studies have reported varied and sometimes disparate outcomes with respect to observed effects on cardiopulmonary ...

Spectral Properties, Generation Order Parameters, and Luminosities for Spin-powered X-Ray Pulsars

NASA Astrophysics Data System (ADS)

Wang, Wei; Zhao, Yongheng

2004-02-01

We show the spectral properties of 15 spin-powered X-ray pulsars, and the correlation between the average power-law photon index and spin-down rate. Generation order parameters (GOPs) based on polar cap models are introduced to characterize the X-ray pulsars. We calculate three definitions of generation order parameters arising from the different effects of magnetic and electric fields on photon absorption during cascade processes, and study the relations between the GOPs and spectral properties of X-ray pulsars. There exists a possible correlation between the photon index and GOP in our pulsar sample. Furthermore, we present a method stemming from the concept of GOPs to estimate the nonthermal X-ray luminosity for spin-powered pulsars. Then X-ray luminosity is calculated in the context of our polar cap accelerator model, which is consistent with most observed X-ray pulsar data. The ratio between the X-ray luminosity estimated by our method and the pulsar's spin-down power is consistent with the LX~10-3Lsd feature.

21 CFR 173.110 - Amyloglucosidase derived from Rhizopus niveus.

Code of Federal Regulations, 2014 CFR

2014-04-01

... SERVICES (CONTINUED) SECONDARY DIRECT FOOD ADDITIVES PERMITTED IN FOOD FOR HUMAN CONSUMPTION Enzyme... enzyme product, consisting of enzyme derived from Rhizopus niveus, and diatomaceous silica as a carrier... enzyme is produced by a process which completely removes the organism Rhizopus niveus from the...

Nanoplasmonic biochips for rapid label-free detection of imidacloprid pesticides with a smartphone.

PubMed

Lee, Kuang-Li; You, Meng-Lin; Tsai, Chia-Hsin; Lin, En-Hung; Hsieh, Shu-Yi; Ho, Ming-Hsun; Hsu, Ju-Chun; Wei, Pei-Kuen

2016-01-15

The widespread and intensive use of neonicotinoid insecticides induces negative cascading effects on ecosystems. It is desirable to develop a portable sensitive sensing platform for on-site screening of high-risk pesticides. We combined an indirect competitive immunoassay, highly sensitive surface plasmon resonance (SPR) biochip and a simple portable imaging setup for label-free detection of imidacloprid pesticides. The SPR biochip consists of several capped nanoslit arrays with different periods which form a spectral image on the chip. The qualitative and semiquantitative analyses of pesticides can be directly observed from the spot shift on the chip. The precise semiquantitative analyses can be further completed by using image processing in a smartphone. We demonstrate simultaneous detection of four different concentrations of imidacloprid pesticides. The visual detection limit is about 1ppb, which is well below the maximum residue concentration permitted by law (20ppb). Compared to the one-step strip assay, the proposed chip is capable of performing semiquantitative analyses and multiple detection. Compared to the enzyme-linked immunosorbent assay, our method is label-free and requires simple washing steps and short reaction time. In addition, the label-free chip has a comparable sensitivity but wider working range than those labeling techniques. Copyright © 2015 Elsevier B.V. All rights reserved.

Transcriptional regulation of xenobiotic detoxification in Drosophila

PubMed Central

Misra, Jyoti R.; Horner, Michael A.; Lam, Geanette; Thummel, Carl S.

2011-01-01

Living organisms, from bacteria to humans, display a coordinated transcriptional response to xenobiotic exposure, inducing enzymes and transporters that facilitate detoxification. Several transcription factors have been identified in vertebrates that contribute to this regulatory response. In contrast, little is known about this pathway in insects. Here we show that the Drosophila Nrf2 (NF-E2-related factor 2) ortholog CncC (cap ‘n’ collar isoform-C) is a central regulator of xenobiotic detoxification responses. A binding site for CncC and its heterodimer partner Maf (muscle aponeurosis fibromatosis) is sufficient and necessary for robust transcriptional responses to three xenobiotic compounds: phenobarbital (PB), chlorpromazine, and caffeine. Genetic manipulations that alter the levels of CncC or its negative regulator, Keap1 (Kelch-like ECH-associated protein 1), lead to predictable changes in xenobiotic-inducible gene expression. Transcriptional profiling studies reveal that more than half of the genes regulated by PB are also controlled by CncC. Consistent with these effects on detoxification gene expression, activation of the CncC/Keap1 pathway in Drosophila is sufficient to confer resistance to the lethal effects of the pesticide malathion. These studies establish a molecular mechanism for the regulation of xenobiotic detoxification in Drosophila and have implications for controlling insect populations and the spread of insect-borne human diseases. PMID:21896655

Structure of Human GIVD Cytosolic Phospholipase A2 Reveals Insights into Substrate Recognition

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

Wang, Hui; Klein, Michael G.; Snell, Gyorgy

Cytosolic phospholipases A2 (cPLA2s) consist of a family of calcium-sensitive enzymes that function to generate lipid second messengers through hydrolysis of membrane-associated glycerophospholipids. The GIVD cPLA2 (cPLA2δ) is a potential drug target for developing a selective therapeutic agent for the treatment of psoriasis. Here, we present two X-ray structures of human cPLA2δ, capturing an apo state, and in complex with a substrate-like inhibitor. Comparison of the apo and inhibitor-bound structures reveals conformational changes in a flexible cap that allows the substrate to access the relatively buried active site, providing new insight into the mechanism for substrate recognition. The cPLA2δ structuremore » reveals an unexpected second C2 domain that was previously unrecognized from sequence alignments, placing cPLA2δ into the class of membrane-associated proteins that contain a tandem pair of C2 domains. Furthermore, our structures elucidate novel inter-domain interactions and define three potential calcium-binding sites that are likely important for regulation and activation of enzymatic activity. These findings provide novel insights into the molecular mechanisms governing cPLA2's function in signal transduction.« less

Temperature Control and Numerical Analysis for Mass Concrete Pile Cap of Hai-huang Bridge

NASA Astrophysics Data System (ADS)

Shi, Han; Hao, Yang; Yong-liang, Wang

2018-05-01

In order to study the heat of hydration in massive concrete, this paper takes Hai-huang bridge for engineering background and uses the finite element analysis software of FEA to analyze the heat of hydration effect of the cushion cap. Comparing the measured data with the theory data, the results showed that the concrete crack was controlled effectively and ensure the construction quality by adopted reasonable temperature control measures. The results of the research prove that the measured data was consistent with calculation data, and it proves the accuracy of the finite element analysis. Finally, the study provides certain reference and guiding significance for similar project.

KSC-04pd0621

NASA Image and Video Library

2004-03-24

KENNEDY SPACE CENTER, FLA. -- In the Thermal Protection System Facility, Pilar Ryan, with United Space Alliance, stitches a piece of insulation blanket for Atlantis' nose cap. Behind her is a cover for the nose cap. The blankets consist of layered, pure silica felt sandwiched between a layer of silica fabric (the hot side) and a layer of S-Glass fabric. The blankets are semi-rigid and can be made as large as 30 inches by 30 inches. The blanket is through-stitched with pure silica thread in a 1-inch grid pattern. After fabrication, the blanket is bonded directly to the vehicle structure and finally coated with a high purity silica coating that improves erosion resistance.

Optical switch based on electrowetting liquid lens

NASA Astrophysics Data System (ADS)

Li, Lei; Liu, Chao; Peng, Hua-Rong; Wang, Qiong-Hua

2012-05-01

In this paper, we propose an optical switch based on an electrowetting liquid lens. The device consists of an electrowetting liquid lens and a non-transparent cap with a pin hole. When the lens is actuated to be positive, the incident light can be converged on the pin hole and pass through the hole with less attenuation. When the lens is deformed to be negative, the incident light is diverged and most of light is blocked by the cap. Our results show that the system can provide high contrast ratio (˜800:1) and reasonable response time (˜88 ms). The proposed optical switch has potential application in light shutters, variable optical attenuators, and adaptive irises.

Chemoenzymatic synthesis of differentially protected 3-deoxysugars

NASA Astrophysics Data System (ADS)

Gillingham, Dennis G.; Stallforth, Pierre; Adibekian, Alexander; Seeberger, Peter H.; Hilvert, Donald

2010-02-01

3-Deoxysugars are important constituents of complex carbohydrates. For example, 2-keto-3-deoxy-D-manno-octulosonic acid (KDO) is an essential component of lipopolysaccharides in Gram-negative bacteria, 2-keto-3-deoxy-D-glycero-D-galacto-nonulosonic acid (KDN) is widely found in carbohydrates of the bacterial cell wall and in lower vertebrates, and sialic acid is a common cap of mammalian glycoproteins. Although ready access to such sugars would benefit the creation of vaccine candidates, antibiotics and small-molecule drugs, their chemical synthesis is difficult. Here we present a simple chemoenzymatic method for preparing differentially protected 3-deoxysugar derivatives from readily available starting materials. It exploits the promiscuous aldolase activity of the enzyme macrophomate synthase (MPS) to add pyruvate enolate diastereoselectively to a wide range of structurally complex aldehydes. A short synthesis of KDN illustrates the utility of this approach. Enzyme promiscuity, which putatively fosters large functional leaps in natural evolution, has great promise as a source of synthetically useful catalytic transformations.

Light and scanning electron microscopy of the ecdysis of Haemonchus contortus infective larvae.

PubMed

Gamble, H R; Lichtenfels, J R; Purcell, J P

1989-04-01

During the second ecdysis of ruminant trichostrongyles, a region of the second molt cuticle is digested by a 44-kDa Zn-metalloprotease. We have examined this digestion process by light and scanning electron microscopy (SEM). The substrate region of the cuticle appeared, during the ecdysis process, as an indented ring at the 20th cuticular annulus coincident with the anterior terminus of the lateral alae. Continued digestion of the cuticle resulted in holes in the ring region that expanded until they became continuous and separation occurred between the anterior and posterior portions of the cuticle. Mechanical movements of the L3 forced aside the cuticle cap that generally remained attached on one side to the posterior portion as the larva escaped from the sheath. The site of secretion of the 44-kDa ecdysing enzyme causing cuticle digestion was not clear from morphological observations; however, existing evidence strongly points to the release of enzyme from the esophageal (pharyngeal) glands through the mouth.

A novel quantum dot-laccase hybrid nanobiosensor for low level determination of dopamine.

PubMed

Shamsipur, Mojtaba; Shanehasz, Maryam; Khajeh, Khosro; Mollania, Nasrin; Kazemi, Sayyed Habib

2012-12-07

This work reports a novel nanobiosensor based on a thioglycolic acid (TGA)-capped CdTe quantum dot-laccase (Lac) enzyme system for sensitive detection of dopamine (DA). The enzyme used catalyzes the oxidation of DA to dopamine-o-quinone (DOQ), which can selectively quench the strong luminescence of CdTe nanocrystals at neutral pH. The relationship between luminescence intensity of CdTe nanocrystals and DA concentration is nicely described by the Stern-Volmer equation. At an optimum pH of 7.4, the proposed sensor gives a linear calibration over a DA concentration range of 0.3 to 100 μM, with a limit of detection of 0.16 μM and a response time of 2 min. The relative standard deviation for seven replicate determinations of 6.0 μM of DA was found to be 3.7%. The sensor was successfully applied to the determination of DA in a blood plasma sample and in a DA injection formulation.

Preparation of lisinopril-capped gold nanoparticles for molecular imaging of angiotensin-converting enzyme

NASA Astrophysics Data System (ADS)

Li, Yuan; Baeta, Cesar; Aras, Omer; Daniel, Marie-Christine

2009-05-01

Overexpression of angiotensin-converting enzyme (ACE) has been associated with the pathophysiology of cardiac and pulmonary fibrosis. Moreover, the prescription of ACE inhibitors, such as lisinopril, has shown a favorable effect on patient outcome for patients with heart failure or systemic hypertension. Thus targeted imaging of the ACE would be of crucial importance for monitoring tissue ACE activity as well as the treatment efficacy in heart failure. In this respect, lisinopril-coated gold nanoparticles were prepared to provide a new type of probe for targeted molecular imaging of ACE by tuned K-edge computed tomography (CT) imaging. The preparation involved non-modified lisinopril, using its primary amine group as the anchoring function on the gold nanoparticles surface. The stable lisinopril-coated gold nanoparticles obtained were characterized by UV-vis spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM). Their zeta potential was also measured in order to assess the charge density on the modified gold nanoparticles (GNPs).

ST5 Observations of the Imbalance of Region 1 and 2 Field-Aligned Currents and Its Implication to the Cross-Polar Cap Pedersen Currents

NASA Technical Reports Server (NTRS)

Le, Guan; Slavin, J. A.; Strangeway, Robert

2011-01-01

In this study, we use the in-situ magnetic field observations from Space Technology 5 mission to quantify the imbalance of Region 1 (R1) and Region 2 (R2) currents. During the three-month duration of the ST5 mission, geomagnetic conditions range from quiet to moderately active. We find that the R1 current intensity is consistently stronger than the R2 current intensity both for the dawnside and the duskside large-scale field-aligned current system. The net currents flowing into (out of) the ionosphere in the dawnside (duskside) are in the order of 5% of the total R1 currents. We also find that the net currents flowing into or out of the ionosphere are controlled by the solar wind-magnetosphere interaction in the same way as the field-aligned currents themselves are. Since the net currents due to the imbalance of the R1 and R2 currents require that their closure currents flow across the polar cap from dawn to dusk as Pedersen currents, our results indicate that the total amount of the cross-polar cap Pedersen currents is in the order of 0.1 MA. This study, although with a very limited dataset, is one of the first attempts to quantify the cross-polar cap Pedersen currents. Given the importance of the Joule heating due to Pedersen currents to the high-latitude ionospheric electrodynamics, quantifying the cross-polar cap Pedersen currents and associated Joule heating is needed for developing models of the magnetosphere-ionosphere coupling.

ST5 Observations of the Imbalance of Region 1 and 2 Field-Aligned Currents and its Implication to the Cross-Polar Cap Pedersen Currents

NASA Technical Reports Server (NTRS)

Le, Guan; Slavin, J. A.; Strangeway, Robert

2010-01-01

In this study, we use the in-situ magnetic field observations from Space Technology 5 mission to quantify the imbalance of Region 1 (R1) and Region 2 (R2) currents. During the three-month duration of the ST5 mission, geomagnetic conditions range from quiet to moderately active. We find that the R1 current intensity is consistently stronger than the R2 current intensity both for the dawnside and the duskside large-scale field-aligned current system. The net currents flowing into (out of) the ionosphere in the dawnside (duskside) are in the order of 5% of the total R1 currents. We also find that the net currents flowing into or out of the ionosphere are controlled by the solar windmagnetosphere interaction in the same way as the field-aligned currents themselves are. Since the net currents due to the imbalance of the R1 and R2 currents require that their closure currents flow across the polar cap from dawn to dusk as Pedersen currents, our results indicate that the total amount of the cross-polar cap Pedersen currents is in the order of approximately 0.1 MA. This study, although with a very limited dataset, is one of the first attempts to quantify the cross-polar cap Pedersen currents. Given the importance of the Joule heating due to Pedersen currents to the high-latitude ionospheric electrodynamics, quantifying the cross-polar cap Pedersen currents and associated Joule heating is needed for developing models of the magnetosphere-ionosphere coupling.

Long term management of patients with cryopyrin-associated periodic syndromes (CAPS): focus on rilonacept (IL-1 Trap)

PubMed Central

Church, Leigh D; Savic, Sinisa; McDermott, Michael F

2008-01-01

Cryopyrin-associated periodic syndromes (CAPS) are a group of inherited inflammatory disorders consisting of familial cold-induced autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID; also known as chronic infantile neurologic, cutaneous, articular [CINCA] syndrome). These rare disorders are associated with heterozygous mutations in the NLRP3 (CIAS1) gene, which encodes the protein NALP3 or cryopyrin, and inflammation driven by excessive production of the cytokine interleukin-1β (IL-1β). Amyloidosis is a serious complication with 25% of MWS patients developing amyloidosis, with occasional fatal consequences, whilst up to 20% of CINCA/NOMID patients die from various complications, before reaching the early adulthood. In some CINCA/NOMID adult survivors amyloidosis can also occur. Prior to the discovery of the CIAS1 gene mutations and the advent of IL-1 targeted therapy, treatment was aimed at suppressing inflammation, with limited success. The selective blockade of IL-1β, with anakinra (IL-1 receptor antagonist), not only provided supportive evidence for the role of IL-1β in CAPS, but also demonstrated the efficacy of targeting IL-1β for treatment of these conditions. In February, 2008, ‘Orphan Drug’ approval from the Food and Drug Administration (FDA) for rilonacept (IL-1 Trap/Arcalyst™, Regeneron Pharmaceuticals, Inc) was given for the treatment of two CAPS disorders, FCAS and MWS in adults and children 12 years and older, making rilonacept the first therapy approved for the treatment of CAPS. PMID:19707454

A comparison of the efficacy of organic and mixed-organic polymers with polyaluminium chloride in chemically assisted primary sedimentation (CAPS).

PubMed

De Feo, G; Galasso, M; Landi, R; Donnarumma, A; De Gisi, S

2013-01-01

CAPS is the acronym for chemically assisted primary sedimentation, which consists of adding chemicals to raw urban wastewater to increase the efficacy of coagulation, flocculation and sedimentation. The principal benefits of CAPS are: upgrading of urban wastewater treatment plants; increasing efficacy of primary sedimentation; and the major production of energy from the anaerobic digestion of primary sludge. Metal coagulants are usually used because they are both effective and cheap, but they can cause damage to the biological processes of anaerobic digestion. Generally, biodegradable compounds do not have these drawbacks, but they are comparatively more expensive. Both metal coagulants and biodegradable compounds have preferential and penalizing properties in terms of CAPS application. The problem can be solved by means of a multi-criteria analysis. For this purpose, a series of tests was performed in order to compare the efficacy of several organic and mixed-organic polymers with that of polyaluminium chloride (PACl) under specific conditions. The multi-criteria analysis was carried out coupling the simple additive weighting method with the paired comparison technique as a tool to evaluate the criteria priorities. Five criteria with the following priorities were used: chemical oxygen demand (COD) removal > turbidity, SV60 > coagulant dose, and coagulant cost. The PACl was the best alternative in 70% of the cases. The CAPS process using PACl made it possible to obtain an average COD removal of 68% compared with 38% obtained, on average, with natural sedimentation and 61% obtained, on average, with the best PACl alternatives (cationic polyacrylamide, natural cationic polymer, dicyandiamide resin).

Characterization of Mars' seasonal caps using neutron spectroscopy

USGS Publications Warehouse

Prettyman, T.H.; Feldman, W.C.; Titus, T.N.

2009-01-01

Mars' seasonal caps are characterized during Mars years 26 and 27 (April 2002 to January 2006) using data acquired by the 2001 Mars Odyssey Neutron Spectrometer. Time-dependent maps of the column abundance of seasonal CO 2 surface ice poleward of 60?? latitude in both hemispheres are determined from spatially deconvolved, epithermal neutron counting data. Sources of systematic error are analyzed, including spatial blurring by the spectrometer's broad footprint and the seasonal variations in the abundance of noncondensable gas at high southern latitudes, which are found to be consistent with results reported by Sprague et al. (2004, 2007). Corrections for spatial blurring are found to be important during the recession, when the column abundance of seasonal CO2 ice has the largest latitude gradient. The measured distribution and inventory of seasonal CO2 ice is compared to simulations by a general circulation model (GCM) calibrated using Viking lander pressure data, cap edge functions determined by thermal emission spectroscopy, and other nuclear spectroscopy data sets. On the basis of the amount of CO2 cycled through the caps during years 26 and 27, the gross polar energy balance has not changed significantly since Viking. The distribution of seasonal CO2 ice is longitudinally asymmetric: in the north, deposition rates of CO2 ice are elevated in Acidalia, which is exposed to katabatic winds from Chasma Borealis; in the south, CO2 deposition is highest near the residual cap. During southern recession, CO 2 ice is present longer than calculated by the GCM, which has implications for the local polar energy balance. Copyright 2009 by the American Geophysical Union.

21 CFR 173.140 - Esterase-lipase derived from Mucor miehei.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN CONSUMPTION Enzyme Preparations and Microorganisms § 173.140 Esterase-lipase derived from Mucor miehei. Esterase-lipase enzyme, consisting of enzyme derived from Mucor miehei var. Cooney et Emerson by... Emerson is nonpathogenic and nontoxic in man or other animals. (c) The enzyme is produced by a process...

21 CFR 173.140 - Esterase-lipase derived from Mucor miehei.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (CONTINUED) SECONDARY DIRECT FOOD ADDITIVES PERMITTED IN FOOD FOR HUMAN CONSUMPTION Enzyme Preparations and Microorganisms § 173.140 Esterase-lipase derived from Mucor miehei. Esterase-lipase enzyme, consisting of enzyme... animals. (c) The enzyme is produced by a process which completely removes the organism Mucor miehei var...

21 CFR 173.140 - Esterase-lipase derived from Mucor miehei.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN CONSUMPTION Enzyme Preparations and Microorganisms § 173.140 Esterase-lipase derived from Mucor miehei. Esterase-lipase enzyme, consisting of enzyme derived from Mucor miehei var. Cooney et Emerson by... Emerson is nonpathogenic and nontoxic in man or other animals. (c) The enzyme is produced by a process...

21 CFR 173.140 - Esterase-lipase derived from Mucor miehei.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN CONSUMPTION Enzyme Preparations and Microorganisms § 173.140 Esterase-lipase derived from Mucor miehei. Esterase-lipase enzyme, consisting of enzyme derived from Mucor miehei var. Cooney et Emerson by... Emerson is nonpathogenic and nontoxic in man or other animals. (c) The enzyme is produced by a process...

21 CFR 173.140 - Esterase-lipase derived from Mucor miehei.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN CONSUMPTION Enzyme Preparations and Microorganisms § 173.140 Esterase-lipase derived from Mucor miehei. Esterase-lipase enzyme, consisting of enzyme derived from Mucor miehei var. Cooney et Emerson by... Emerson is nonpathogenic and nontoxic in man or other animals. (c) The enzyme is produced by a process...

Investigating Viruses during the Transformation of Molecular Biology

PubMed Central

2017-01-01

This Reflections article describes my early work on viral enzymes and the discovery of mRNA capping, how my training in medicine and biochemistry merged as I evolved into a virologist, the development of viruses as vaccine vectors, and how scientific and technological developments during the 1970s and beyond set the stage for the interrogation of nearly every step in the reproductive cycle of vaccinia virus (VACV), a large DNA virus with about 200 genes. The reader may view this article as a work in progress, because I remain actively engaged in research at the National Institutes of Health (NIH) notwithstanding 50 memorable years there. PMID:28154190

A theranostic dental pulp capping agent with improved MRI and CT contrast and biological properties.

PubMed

Mastrogiacomo, S; Güvener, N; Dou, W; Alghamdi, H S; Camargo, W A; Cremers, J G O; Borm, P J A; Heerschap, A; Oosterwijk, E; Jansen, J A; Walboomers, X F

2017-10-15

Different materials have been used for vital dental pulp treatment. Preferably a pulp capping agent should show appropriate biological performance, excellent handling properties, and a good imaging contrast. These features can be delivered into a single material through the combination of therapeutic and diagnostic agents (i.e. theranostic). Calcium phosphate based composites (CPCs) are potentially ideal candidate for pulp treatment, although poor imaging contrast and poor dentino-inductive properties are limiting their clinical use. In this study, a theranostic dental pulp capping agent was developed. First, imaging properties of the CPC were improved by using a core-shell structured dual contrast agent (csDCA) consisting of superparamagnetic iron oxide (SPIO) and colloidal gold, as MRI and CT contrast agent respectively. Second, biological properties were implemented by using a dentinogenic factor (i.e. bone morphogenetic protein 2, BMP-2). The obtained CPC/csDCA/BMP-2 composite was tested in vivo, as direct pulp capping agent, in a male Habsi goat incisor model. Our outcomes showed no relevant alteration of the handling and mechanical properties (e.g. setting time, injectability, and compressive strength) by the incorporation of csDCA particles. In vivo results proved MRI contrast enhancement up to 7weeks. Incisors treated with BMP-2 showed improved tertiary dentin deposition as well as faster cement degradation as measured by µCT assessment. In conclusion, the presented theranostic agent matches the imaging and regenerative requirements for pulp capping applications. In this study, we combined diagnostic and therapeutic agents in order to developed a theranostic pulp capping agent with enhanced MRI and CT contrast and improved dentin regeneration ability. In our study we cover all the steps from material preparation, mechanical and in vitro characterization, to in vivo study in a goat dental model. To the best of our knowledge, this is the first time that a theranostic pulp capping material have been developed and tested in an in vivo animal model. Our promising results in term of imaging contrast enhancement and of induction of new dentin formation, open a new scenario in the development of innovative dental materials. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Psychometric properties of the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (PCL-5) in veterans.

PubMed

Bovin, Michelle J; Marx, Brian P; Weathers, Frank W; Gallagher, Matthew W; Rodriguez, Paola; Schnurr, Paula P; Keane, Terence M

2016-11-01

This study examined the psychometric properties of the posttraumatic stress disorder (PTSD) Checklist for Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (PCL-5; Weathers, Litz, et al., 2013b) in 2 independent samples of veterans receiving care at a Veterans Affairs Medical Center (N = 468). A subsample of these participants (n = 140) was used to define a valid diagnostic cutoff score for the instrument using the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5; Weathers, Blake, et al., 2013) as the reference standard. The PCL-5 test scores demonstrated good internal consistency (α = .96), test-retest reliability (r = .84), and convergent and discriminant validity. Consistent with previous studies (Armour et al., 2015; Liu et al., 2014), confirmatory factor analysis revealed that the data were best explained by a 6-factor anhedonia model and a 7-factor hybrid model. Signal detection analyses using the CAPS-5 revealed that PCL-5 scores of 31 to 33 were optimally efficient for diagnosing PTSD (κ(.5) = .58). Overall, the findings suggest that the PCL-5 is a psychometrically sound instrument that can be used effectively with veterans. Further, by determining a valid cutoff score using the CAPS-5, the PCL-5 can now be used to identify veterans with probable PTSD. However, findings also suggest the need for research to evaluate cluster structure of DSM-5. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

The origin of 17O-depleted barite in Neoproterozoic cap carbonates in South China: A sedimentological perspective

NASA Astrophysics Data System (ADS)

Zhou, C.; Bao, H.; Yuan, X.

2009-12-01

Barite deposits are known from the Marinoan cap carbonate sequence in NW Africa, NW Canada, and many other localities worldwide, including South China, where the barite has been found to have distinct, non-mass-dependent depletion in 17O. It has been proposed that the negative anomalies most likely reflect an extremely high pCO2 atmosphere at the initiation of a global glacial meltdown. While widespread in occurrence and distinct in isotopic composition, the barite’s origin remains elusive. Field observation shows that the 17O-anomalous barite occurs only at one specific horizon/surface of the cap dolostone. A satisfying formation model based on geochemical data for the barite must corroborate evidence from geological, tectonic, sedimentological, and petrographic contexts. The Nantuo glacial deposit (Marinoan in age) and its cap carbonate occur widely on the Yangtze Block of South China. The thickness of the Nantuo tillites increases evidently from the shallow platform to basinal settings. The overlying cap carbonates, consisting mainly of dolostone, however, are generally around 3~4 meters thick and remain relatively stable on the Yangtze Block. There is a widespread occurrence of voids and cavities in the lower part of cap dolostones, in both shallow platform facies and transitional zones of the Yangtze Block. Barite deposits occur as fans or coatings on pre-existing surfaces or on walls of voids and fractures, probably marking a synchronous event affecting the entire Yangtze Block. Void and cavity fills generally start with aragonite crystal fans and barite fans, followed by opal (silica) or quartz, or calcite. The remaining space was finally filled with large blocky calcite crystals in shallower settings or pyrite crystals in deeper settings. We propose that the voids and cavities are the result of carbonate dissolution after the initial deposition of cap dolostones. The dissolution may imply a regional or even a global sedimentation hiatus during the deposition of Marinoan cap carbonates. One possibility is that the initially deposited cap carbonate may have been uplifted into a zone influenced by meteoric water due to glacioeustasy and lithospheric rebound as a result of a quick unloading of a massive continental ice cap on the Yangtze Block. Karstic dissolution has also been recognized in cap dolostones in NW Africa and NW Canada. While the voids and cavities in South China may be of a similar karst origin as those in NM Africa, sedimentological evidence, together with multiple sulfur and oxygen isotope data, suggests that the precipitation of the barite in South China may be related to an episode of free Ba2+ supply from deep, anoxic water, in association with a transgression (instead of an sea-level fall) after a karst dissolution. Thus, we suggest that SO42- was present in seawater prior to the beginning of Marinoan meltdown. It was the Ba2+ supply that limited the occurrence of barite to specific stratigraphic horizons in the cap carbonates. If the above inference is true, the 17O-depleted barite has recorded an atmospheric/hydrological condition well after the initial meltdown of the Marinoan "snowball" Earth.

Exercise enhance the ectopic bone formation of calcium phosphate biomaterials in muscles of mice.

PubMed

Cheng, Lijia; Yan, Shuo; Zhu, Jiang; Cai, Peiling; Wang, Ting; Shi, Zheng

2017-08-01

To investigate whether exercise can enhance ectopic bone formation of calcium phosphate (Ca-P) biomaterials in muscles of mice. Firstly, ten transient receptor potential vanilloid subfamily member 1 (TRPV1) knockout mice (group KO) and ten C57BL/6 mice (group WT) were randomly chosen, 10μg Ca-P biomaterials were implanted into the thigh muscle pouch of each mouse which was far away from femur; after that, all animals were kept in open field for free exploration 5min, and the movement time and distance were automatically analyzed. Ten weeks later, the Ca-P samples were harvested for histological staining and immunochemistry. Secondly, the Ca-P biomaterials were implanted into the thigh muscle pouch of C57BL/6 mice the same as previous operation, and then randomly divided into two groups: running group and non-running group (n=10); in running group, all mice run 1h as a speed of 6m/h in a treadmill for 10weeks. Ten weeks later, the blood was collected to detect the interleukin-4 (IL-4) and IL-12 levels by enzyme linked immunosorbent assay (ELISA), and the samples were harvested for histological staining. In groups KO and WT, both the movement time and distance were significant higher in group KO than that in group WT (P<0.05); furthermore, the histology staining results showed that lots of new bone and bone marrow tissues were observed in group KO, but only bone matrix-like substances were observed in group WT. In running group and non-running group, the ELISA results indicated that the immunological genes, both IL-4 and IL-12 levels were significant higher in running group than that in non-running group (P<0.05); besides that, more new bone tissues were observed in running group than that in non-running group. Knockout of TRPV1 in mice could reduce algesia and induce the stronger athletic ability of mice, causing better osteoinductivity of Ca-P biomaterials both in TRPV1 -/- mice and running mice; according to this, we want to offer a proposal to patients who suffer from bone defects and artificial bone transplantation: do moderate exercise, don't convalesce all the time. Copyright © 2017 Elsevier B.V. All rights reserved.

Purification and characterization of two fully deuterated enzymes

NASA Technical Reports Server (NTRS)

Crespi, H. L.; Katz, J. J.; Parmerter, S.; Rokop, S.

1969-01-01

Comparative data reveal little difference between kinetic and thermal stabilities of pure preparations of two ordinary enzymes and their fully deuterated counterparts. The effects of temperature on the enzymes proved to be consistent with earlier results.

A geospatial model to quantify mean thickness of peat in cranberry bogs

USDA-ARS?s Scientific Manuscript database

Commercial cranberry (Vaccinium macrocarpon Ait.) is cultivated on peatlands, which consist of sedimentary deposits of peat capped by a 0.3-1 m of artificial sand. Despite distinct soil layering, a general paucity of information exists on the physical properties of cranberry bogs. Field measurements...

A geospatial model to quantify mean thickness of peat in cranberry bogs

USDA-ARS?s Scientific Manuscript database

Commercial cranberry (Vaccinium macrocarpon Ait.) is cultivated on peatlands, which consist of sedimentary deposits of peat capped by a 0.3-1 m of artificial sand. Despite distinct soil layering, a general paucity of information exists on the physical properties of cranberry bogs. Field measurement...

'A unique 5’ translation element discoverd in Triticum mosaic virus'

USDA-ARS?s Scientific Manuscript database

Many RNA viruses rely on internal ribosome entry site (IRES) elements to deviate from the canonical cap-dependent translation mechanism. In contrast to the well-defined IRES elements found in animal viruses, plant viral IRESes identified to date reportedly consist of relatively short, ill-defined se...

The Microstructural Response of Granular Soil Under Uniaxial Strain

DTIC Science & Technology

1993-10-01

under uniaxial strains of up to 10 percent. The material tested was a poorly graded ottowa sand with specimens consisting of either 0.5- or 0.75-mm...microstructural effects in granular material under uniaxial strain of up to 10.0 percent. The relative influence of several microstructural effects (such as...uniaxial strain. The confinement vessel consisted of a base plate, four walls, and a loading cap. The sidewalls extended up beyond the specimen and served

A GCM Recent History of Northern Martian Polar Layered Deposits: Contribution from Past Equatorial Ice Reservoirs

NASA Technical Reports Server (NTRS)

Levrard, B.; Laskar, J.; Montmessin, F.; Forget, F.

2005-01-01

Polar layered deposits are exposed in the walls of the troughs cutting the north polar cap of Mars. They consist of alternating ice and dust layers or layers of an ice-dust mixture with varying proportions and are found throughout the cap. Layers thickness ranges from meters to several tens of meters with an approximately 30 meter dominant wavelength. Although their formation processes is not known, they are presumed to reflect changes in ice and dust stability over orbital and axial variations. Intensive 3-D LMD GCM simulations of the martian water cycle have been thus performed to determine the annual rates of exchange of surface ice between the northern cap and tropical areas for a wide range of obliquity and orbital parameters values.These rates have been employed to reconstruct an history of the northern cap and test simple models of dust-ice layers formation over the last 10 Ma orbital variations. We use the 3-D water cycle model simulated by the 3-D LMD GCM with an intermediate grid resolution (7.5 longitude x 5.625 latitude) and 25 vertical levels. The dust opacity is constant and set to 0,15. No exchange of ice with regolith is allowed. The evolution of the northern cap over obliquity and orbital changes (eccentricity, Longitude of perihelion) has been recently described with this model. High summer insolation favors transfer of ice from the northern pole to the Tharsis and Olympus Montes, while at low obliquity, unstable equatorial ice is redeposited in high-latitude and polar areas of both hemisphere. The disappearance of the equatorial ice reservoir leads to a poleward recession of icy high latitude reservoirs, providing an additional source for the cap accumulation during each obliquity or orbital cycle. Furthering the efforts, a quantitative evolution of ice reservoirs is here investigated for various astronomical conditions.

Updated greenhouse gas and criteria air pollutant emission factors and their probability distribution functions for electricity generating units

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

Cai, H.; Wang, M.; Elgowainy, A.

Greenhouse gas (CO{sub 2}, CH{sub 4} and N{sub 2}O, hereinafter GHG) and criteria air pollutant (CO, NO{sub x}, VOC, PM{sub 10}, PM{sub 2.5} and SO{sub x}, hereinafter CAP) emission factors for various types of power plants burning various fuels with different technologies are important upstream parameters for estimating life-cycle emissions associated with alternative vehicle/fuel systems in the transportation sector, especially electric vehicles. The emission factors are typically expressed in grams of GHG or CAP per kWh of electricity generated by a specific power generation technology. This document describes our approach for updating and expanding GHG and CAP emission factors inmore » the GREET (Greenhouse Gases, Regulated Emissions, and Energy Use in Transportation) model developed at Argonne National Laboratory (see Wang 1999 and the GREET website at http://greet.es.anl.gov/main) for various power generation technologies. These GHG and CAP emissions are used to estimate the impact of electricity use by stationary and transportation applications on their fuel-cycle emissions. The electricity generation mixes and the fuel shares attributable to various combustion technologies at the national, regional and state levels are also updated in this document. The energy conversion efficiencies of electric generating units (EGUs) by fuel type and combustion technology are calculated on the basis of the lower heating values of each fuel, to be consistent with the basis used in GREET for transportation fuels. On the basis of the updated GHG and CAP emission factors and energy efficiencies of EGUs, the probability distribution functions (PDFs), which are functions that describe the relative likelihood for the emission factors and energy efficiencies as random variables to take on a given value by the integral of their own probability distributions, are updated using best-fit statistical curves to characterize the uncertainties associated with GHG and CAP emissions in life-cycle modeling with GREET.« less

Minimization of material inter-diffusion for thermally stable quaternary-capped InAs quantum dot via strain modification

NASA Astrophysics Data System (ADS)

Ghadi, Hemant; Sehara, Navneet; Murkute, Punam; Chakrabarti, Subhananda

2017-05-01

In this study, a theoretical model is developed for investigating the effect of thermal annealing on a single-layer quaternary-capped (In0.21Al0.21Ga0.58As) InAs quantum dot heterostructure (sample A) and compared to a conventional GaAs-capped sample (sample B). Strain, an interfacial property, aids in dot formation; however, it hinders interdiffusion (up to 650 °C), rendering thermal stability to heterostructures. Three diffusing species In/Al/Ga intermix because of the concentration gradient and temperature variation, which is modeled by Fick's law of diffusion. Ground-state energy for both carriers (electron and holes) is calculated by the Schrodinger equation at different annealing temperatures, incorporating strain computed by the concentration-dependent model. Change in activation energy due to strain decreases particle movement, thereby resulting in thermally stable structures at low annealing temperatures. At low temperature, the conduction band near the dot edge slightly decreases, attributed to the comparatively high strain. Calculated results are consistent with the experimental blue-shift i.e. towards lower wavelength of photoluminescence peak on the same sample with increasing annealing temperatures. Cross-sectional transmission microscopy (TEM) images substantiate the existence of dot till 800 °C for sample (A). With increasing annealing temperature, interdiffusion and dot sublimation are observed in XTEM images of samples A and B. Strain calculated from high-resolution X-ray diffraction (HRXRD) peaks and its decline with increasing temperature are in agreement with that calculated by the model. For highlighting the benefits of quaternary capping, InAlGaAs capping is theoretically and experimentally compared to GaAs capping. Concentration-dependent strain energy is calculated at every point and is further used for computing material interdiffusion, band profiles, and photoluminescence peak wavelength, which can provide better insights into strain energy behavior with temperature and help in the better understanding of thermal annealing.

A novel "dual-potential" electrochemiluminescence aptasensor array using CdS quantum dots and luminol-gold nanoparticles as labels for simultaneous detection of malachite green and chloramphenicol.

PubMed

Feng, Xiaobin; Gan, Ning; Zhang, Huairong; Yan, Qing; Li, Tianhua; Cao, Yuting; Hu, Futao; Yu, Hongwei; Jiang, Qianli

2015-12-15

A novel type of "dual-potential" electrochemiluminescence (ECL) aptasensor array was fabricated on a homemade screen-printed carbon electrode (SPCE) for simultaneous detection of malachite green (MG) and chloramphenicol (CAP) in one single assay. The SPCE substrate consisted of a common Ag/AgCl reference electrode, carbon counter electrode and two carbon working electrodes (WE1 and WE2). In the system, CdS quantum dots (QDs) were modified on WE1 as cathode ECL emitters and luminol-gold nanoparticles (L-Au NPs) were modified on WE2 as anode ECL emitters. Then the MG aptamer complementary strand (MG cDNA) and CAP aptamer complementary strand (CAP cDNA) were attached on CdS QDs and L-Au NPs, respectively. The cDNA would hybridize with corresponding aptamer that was respectively tagged with cyanine dye (Cy5) (as quenchers of CdS QDs) and chlorogenic acid (CA) (as quenchers of l-Au NPs) using poly(ethylenimine) (PEI) as a bridging agent. PEI could lead to a large number of quenchers on the aptamer, which increased the quenching efficiency. Upon MG and CAP adding, the targets could induce strand release due to the highly affinity of analytes toward aptamers. Meanwhile, it could release the Cy5 and CA, which recovered cathode ECL of CdS QDs and anode ECL of L-Au NPs simultaneously. This "dual-potential" ECL strategy could be used to detect MG and CAP with the linear ranges of 0.1-100 nM and 0.2-150 nM, with detection limits of 0.03 nM and 0.07 nM (at 3sB), respectively. More importantly, this designed method was successfully applied to determine MG and CAP in real fish samples and held great potential in the food analysis. Copyright © 2015 Elsevier B.V. All rights reserved.

Contrast Sensitivity Perimetry and Clinical Measures of Glaucomatous Damage

PubMed Central

Swanson, William H.; Malinovsky, Victor E.; Dul, Mitchell W.; Malik, Rizwan; Torbit, Julie K.; Sutton, Bradley M.; Horner, Douglas G.

2014-01-01

ABSTRACT Purpose To compare conventional structural and functional measures of glaucomatous damage with a new functional measure—contrast sensitivity perimetry (CSP-2). Methods One eye each was tested for 51 patients with glaucoma and 62 age-similar control subjects using CSP-2, size III 24-2 conventional automated perimetry (CAP), 24-2 frequency-doubling perimetry (FDP), and retinal nerve fiber layer (RNFL) thickness. For superior temporal (ST) and inferior temporal (IT) optic disc sectors, defect depth was computed as amount below mean normal, in log units. Bland-Altman analysis was used to assess agreement on defect depth, using limits of agreement and three indices: intercept, slope, and mean difference. A criterion of p < 0.0014 for significance used Bonferroni correction. Results Contrast sensitivity perimetry-2 and FDP were in agreement for both sectors. Normal variability was lower for CSP-2 than for CAP and FDP (F > 1.69, p < 0.02), and Bland-Altman limits of agreement for patient data were consistent with variability of control subjects (mean difference, −0.01 log units; SD, 0.11 log units). Intercepts for IT indicated that CSP-2 and FDP were below mean normal when CAP was at mean normal (t > 4, p < 0.0005). Slopes indicated that, as sector damage became more severe, CAP defects for IT and ST deepened more rapidly than CSP-2 defects (t > 4.3, p < 0.0005) and RNFL defects for ST deepened more slowly than for CSP, FDP, and CAP. Mean differences indicated that FDP defects for ST and IT were on average deeper than RNFL defects, as were CSP-2 defects for ST (t > 4.9, p < 0.0001). Conclusions Contrast sensitivity perimetry-2 and FDP defects were deeper than CAP defects in optic disc sectors with mild damage and revealed greater residual function in sectors with severe damage. The discordance between different measures of glaucomatous damage can be accounted for by variability in people free of disease. PMID:25259758

Contrast sensitivity perimetry and clinical measures of glaucomatous damage.

PubMed

Swanson, William H; Malinovsky, Victor E; Dul, Mitchell W; Malik, Rizwan; Torbit, Julie K; Sutton, Bradley M; Horner, Douglas G

2014-11-01

To compare conventional structural and functional measures of glaucomatous damage with a new functional measure-contrast sensitivity perimetry (CSP-2). One eye each was tested for 51 patients with glaucoma and 62 age-similar control subjects using CSP-2, size III 24-2 conventional automated perimetry (CAP), 24-2 frequency-doubling perimetry (FDP), and retinal nerve fiber layer (RNFL) thickness. For superior temporal (ST) and inferior temporal (IT) optic disc sectors, defect depth was computed as amount below mean normal, in log units. Bland-Altman analysis was used to assess agreement on defect depth, using limits of agreement and three indices: intercept, slope, and mean difference. A criterion of p < 0.0014 for significance used Bonferroni correction. Contrast sensitivity perimetry-2 and FDP were in agreement for both sectors. Normal variability was lower for CSP-2 than for CAP and FDP (F > 1.69, p < 0.02), and Bland-Altman limits of agreement for patient data were consistent with variability of control subjects (mean difference, -0.01 log units; SD, 0.11 log units). Intercepts for IT indicated that CSP-2 and FDP were below mean normal when CAP was at mean normal (t > 4, p < 0.0005). Slopes indicated that, as sector damage became more severe, CAP defects for IT and ST deepened more rapidly than CSP-2 defects (t > 4.3, p < 0.0005) and RNFL defects for ST deepened more slowly than for CSP, FDP, and CAP. Mean differences indicated that FDP defects for ST and IT were on average deeper than RNFL defects, as were CSP-2 defects for ST (t > 4.9, p < 0.0001). Contrast sensitivity perimetry-2 and FDP defects were deeper than CAP defects in optic disc sectors with mild damage and revealed greater residual function in sectors with severe damage. The discordance between different measures of glaucomatous damage can be accounted for by variability in people free of disease.

The Martian North Polar Cap in Summer - One Year Later

NASA Technical Reports Server (NTRS)

2001-01-01

In the middle of January 2001, Mars Global Surveyor (MGS) completed one Mars year in its 380 km-high (236 mi) mapping orbit. The mapping orbit was originally achieved in late February 1999. In March of that year, MGS conducted a series of operations in preparation for full-up mapping, first calibrating its scientific instruments and then operating in a mode in which the high gain antenna was held fixed against the body of the spacecraft. During this Fixed High Gain Antenna period, 'contingency science' observations were made in case the high gain antenna failed to properly deploy. The wide angle view of the martian north polar cap shown on the left was acquired on March 13, 1999, during early northern summer. The image on the right was acquired almost exactly one Mars year later, on January 26, 2001. The light-toned surfaces are residual water ice that remains through the summer season. The nearly circular band of dark material surrounding the cap consists mainly of sand dunes formed and shaped by wind. The north polar cap is roughly 1100 kilometers (680 miles) across. Close inspection will show that there are differences in the frost cover between the two images (for example, in the upper center of each image, and on the left edge center). Although these changes appear small, they are in fact quite large--the change in frost covering is equivalent to the amount of frost that would be evaporated (in the case of areas that are darker) or deposited (in areas where frost is still on the ground) in almost 5 months. What gives rise to such large changes in the heat budget for the polar caps from one year to the next is not known. Changes in the coloration and brightness of the polar cap suggest dust, deposited perhaps by dust storms during critical periods of the year, may play an important role.

Point-of-care Helicobacter pylori urine antibody detection in a multi-ethnic adult population in the United States.

PubMed

Opekun, Antone R; Luu, Phong; Gotschall, Ann B; Abdalla, Nageeb; Torres, Elizabeth; Rudd, Summer B; Graham, David Y; Nurgalieva, Zhannat Z; Tsuchiya, Kyoko

2006-07-01

A need exists for accurate point-of-care tests for diagnosis of Helicobacter pylori (H. pylori) infection to evaluate a rapid urine-H. pylori antibody test device for detection of H. pylori infection in a point-of-care setting in the United States. A multi-center study in a multi-ethnic population compared the RAPIRUN urine antibody test with the (13)C-urea breath test (C-UBT) and a traditional serologic test, the high-molecular-weight cell-associated protein enzyme immunoassay (HM-CAP EIA). The primary comparator was with "definite positive" and "definite negative" patients defined as a concordance of combined results of the UBT and the HM-CAP IgG EIA. Overall, 188 eligible patients were enrolled (61 men, age range: 18-73 years, including 84 Hispanics, 73 Asian-Pacific Americans, 22 Black African-Americans, 6 non-Hispanic Caucasians, and 3 of "other" ethnicity). Compared with "definite positive" and "definite negative" results, the sensitivity and specificity of the urine antibody test were 0.9 and 1.0, respectively. The urine antibody test proved suitable for point-of-care rapid diagnosis of anti-H. pylori antibodies indicative of active or past H. pylori infection.

Multiple receptors mobilize calcium through a pertussis toxin (PT) sensitive GTP-binding protein in human neutrophils (PMN's)

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

Lad, P.M.; Olson, C.V.; Grewal, I.S.

1986-03-05

Treatment of PMN's with PT causes an abolition of chemotaxis, enzyme release, superoxide generation and aggregation caused by f-met-leu-phe (FMLP),C5a and platelet activating factor (PAF). Lectin (Con-A) induced capping and receptor induced shape change are abolished, but phagocytosis is unaltered. In whole cells, calcium mobilization induced by FMLP, PAF and Con-A inhibited by PT although the FMLP-mediated effect is more susceptible to PT's effects. Treatment of PMN's with phorbol 12-myristate 13 acetate (PMA) causes an abolition of calcium mobilization by all agents in a range which also inhibits cap formation. Investigation of calcium uptake reveals PT sensitive and insensitive components.more » Reciprocal interactions between Ns and Ni proteins are also observed since pretreatment with FMLP and PAF causes a stimulation of Ns-mediated cyclic AMP enhancement while pretreatment with Ns linked receptors (PGE/sub 1/ and beta receptor agonists) inhibits calcium mobilization. Comparative peptide mapping studies indicate substantial similarity between Ni proteins in PMN's, platelets and human erythrocytes. The authors results suggest that the Ni linked calcium mobilization sensitive to PMA is important to the regulation of the human neutrophil.« less

Enzyme activities in parotid saliva of patients with the restrictive type of anorexia nervosa.

PubMed

Paszynska, Elzbieta; Slopien, Agnieszka; Dmitrzak-Weglarz, Monika; Hannig, Christian

2017-04-01

In patients with anorexia nervosa (AN) specific signs may occur in the oral cavity, but there are conflicting reports about their significance, especially concerning changes in salivary composition. The aim of this clinical study was to evaluate the resting parotid flow rate (PFR) and the activity of the following enzymes in parotid saliva: amylase, aspartate amino transferase (AST), lysozyme, peroxidase, serine and acidic proteases in the acute phase of the restrictive type of AN and to compare the findings with those in healthy controls. Forty-one subjects participated (20 patients with AN, 21 matched healthy controls), parotid saliva was collected using a modified Lashley cap at rest. Enzyme activities were measured with fluorimetric and photometric assays. The unstimulated PFR was significantly lower than in the controls, lysozyme and AST activity was significantly lower, and amylase showed a high inter-individual variability. A positive correlation for amylase and lysozyme and negative ones for lysozyme and BMI, lysozyme and IBW%, serine protease and salivary flow were observed. The reduced PFR and enzyme activities levels suggest that AN does not only affect the quantity of the saliva but also its quality and, its biological functions. The results obtained should help to provide a better understanding of the effect of AN disease on the pathogenesis of at least some oral diseases. Further research is needed on any possible role of reduced lysozyme and transaminase activity in maintaining oral protection against external toxic agents and bacteria. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Effects of Crystal Phase and Particle Morphology of Calcium Phosphates on Proliferation and Differentiation of Human Mesenchymal Stromal Cells.

PubMed

Danoux, Charlène; Pereira, Daniel; Döbelin, Nicola; Stähli, Christoph; Barralet, Jake; van Blitterswijk, Clemens; Habibovic, Pamela

2016-07-01

Calcium phosphate (CaP) ceramics are extensively used for bone regeneration; however, their clinical performance is still considered inferior to that of patient's own bone. To improve the performance of CaP bone graft substitutes, it is important to understand the effects of their individual properties on a biological response. The aim of this study is to investigate the effects of the crystal phase and particle morphology on the behavior of human mesenchymal stromal cells (hMSCs). To study the effect of the crystal phase, brushite, monetite, and octacalcium phosphate (OCP) are produced by controlling the precipitation conditions. Brushite and monetite are produced as plate-shaped and as needle-shaped particles, to further investigate the effect of particle morphology. Proliferation of hMSCs is inhibited on OCP as compared to brushite and monetite in either morphology. Brushite needles consistently show the lowest expression of most osteogenic markers, whereas the expression on OCP is in general high. There is a trend toward a higher expression of the osteogenic markers on plate-shaped than on needle-shaped particles for both brushite and monetite. Within the limits of CaP precipitation, these data indicate the effect of both crystal phase and particle morphology of CaPs on the behavior of hMSCs. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microwave-Assisted Hydrothermal Rapid Synthesis of Calcium Phosphates: Structural Control and Application in Protein Adsorption

PubMed Central

Cai, Zhu-Yun; Peng, Fan; Zi, Yun-Peng; Chen, Feng; Qian, Qi-Rong

2015-01-01

Synthetic calcium phosphate (CaP)-based materials have attracted much attention in the biomedical field. In this study, we have investigated the effect of pH values on CaP nanostructures prepared using a microwave-assisted hydrothermal method. The hierarchical nanosheet-assembled hydroxyapatite (HAP) nanostructure was prepared under weak acidic conditions (pH 5), while the HAP nanorod was prepared under neutral (pH 7) and weak alkali (pH 9) condition. However, when the pH value increases to 11, a mixed product of HAP nanorod and tri-calcium phosphate nanoparticle was obtained. The results indicated that the pH value of the initial reaction solution played an important role in the phase and structure of the CaP. Furthermore, the protein adsorption and release performance of the as-prepared CaP nanostructures were investigated by using hemoglobin (Hb) as a model protein. The sample that was prepared at pH = 11 and consisted of mixed morphologies of nanorods and nanoprisms showed a higher Hb protein adsorption capacity than the sample prepared at pH 5, which could be explained by its smaller size and dispersed structure. The results revealed the relatively high protein adsorption capacity of the as-prepared CaP nanostructures, which show promise for applications in various biomedical fields such as drug delivery and protein adsorption. PMID:28347064

Microwave-Assisted Hydrothermal Rapid Synthesis of Calcium Phosphates: Structural Control and Application in Protein Adsorption.

PubMed

Cai, Zhu-Yun; Peng, Fan; Zi, Yun-Peng; Chen, Feng; Qian, Qi-Rong

2015-07-31

Synthetic calcium phosphate (CaP)-based materials have attracted much attention in the biomedical field. In this study, we have investigated the effect of pH values on CaP nanostructures prepared using a microwave-assisted hydrothermal method. The hierarchical nanosheet-assembled hydroxyapatite (HAP) nanostructure was prepared under weak acidic conditions (pH 5), while the HAP nanorod was prepared under neutral (pH 7) and weak alkali (pH 9) condition. However, when the pH value increases to 11, a mixed product of HAP nanorod and tri-calcium phosphate nanoparticle was obtained. The results indicated that the pH value of the initial reaction solution played an important role in the phase and structure of the CaP. Furthermore, the protein adsorption and release performance of the as-prepared CaP nanostructures were investigated by using hemoglobin (Hb) as a model protein. The sample that was prepared at pH = 11 and consisted of mixed morphologies of nanorods and nanoprisms showed a higher Hb protein adsorption capacity than the sample prepared at pH 5, which could be explained by its smaller size and dispersed structure. The results revealed the relatively high protein adsorption capacity of the as-prepared CaP nanostructures, which show promise for applications in various biomedical fields such as drug delivery and protein adsorption.

Effects of dietary aluminum, calcium, and phosphorus on egg and bone of European starlings

USGS Publications Warehouse

Miles, A.K.; Grue, C.E.; Pendleton, G.W.; Soares, J.H.

1993-01-01

Egg and bone of passerine birds nesting in acidified habitats may be affected by high levels of Al or P, or low levels of Ca. Nine treatments of three levels of dietary Al (target levels of 200, 1,000, and 5,000 ?g/g) and three levels of Ca:P (target levels of NN = 1.3% Ca: 0.9% P; LL = 0.19 Ca:0.45 P; LH = 0.19 Ca:1.65 P) were fed to 16-17 starling pairs during two breeding seasons. Eggs of starlings fed the LH diet were smaller and weighed less than eggs from the NN and LL treatments. Treatment effects on thickness, strength, and weight of eggshells were not consistent between seasons, probably because of differences in actual dietary levels of AI, Ca, and P or in incubation intervals. In one season, birds fed the highest Al diet had thicker eggshells than those from the other Al treatments (no effect from Ca:P); the following season, eggshells from the NN and LH treatments were thicker and stronger than those from the LL treatment. Eggshells from the NN treatment weighed more than those from the other Ca:P treatments. Starlings on the LH diet had the strongest femurs, but the effect was interactive with different levels of dietary AI. Effects of Ca:P on egg and bone were more evident than Al effects.

Impact of human population history on distributions of individual-level genetic distance

PubMed Central

2005-01-01

Summaries of human genomic variation shed light on human evolution and provide a framework for biomedical research. Variation is often summarised in terms of one or a few statistics (eg FST and gene diversity). Now that multilocus genotypes for hundreds of autosomal loci are available for thousands of individuals, new approaches are applicable. Recently, trees of individuals and other clustering approaches have demonstrated the power of an individual-focused analysis. We propose analysing the distributions of genetic distances between individuals. Each distribution, or common ancestry profile (CAP), is unique to an individual, and does not require a priori assignment of individuals to populations. Here, we consider a range of models of population history and, using coalescent simulation, reveal the potential insights gained from a set of CAPs. Information lies in the shapes of individual profiles -- sometimes captured by variance of individual CAPs -- and the variation across profiles. Analysis of short tandem repeat genotype data for over 1,000 individuals from 52 populations is consistent with dramatic differences in population histories across human groups. PMID:15814064

Results of Uranium Dioxide-Tungsten Irradiation Test and Post-Test Examination

NASA Technical Reports Server (NTRS)

Collins, J. F.; Debogdan, C. E.; Diianni, D. C.

1973-01-01

A uranium dioxide (UO2) fueled capsule was fabricated and irradiated in the NASA Plum Brook Reactor Facility. The capsule consisted of two bulk UO2 specimens clad with chemically vapor deposited tungsten (CVD W) 0.762 and 0.1016 cm (0.030-and 0.040-in.) thick, respectively. The second specimen with 0.1016-cm (0.040-in.) thick cladding was irradiated at temperature for 2607 hours, corresponding to an average burnup of 1.516 x 10 to the 20th power fissions/cu cm. Postirradiation examination showed distortion in the bottom end cap, failure of the weld joint, and fracture of the central vent tube. Diametral growth was 1.3 percent. No evidence of gross interaction between CVD tungsten or arc-cast tungsten cladding and the UO2 fuel was observed. Some of the fission gases passed from the fuel cavity to the gas surrounding the fuel specimen via the vent tube and possibly the end-cap weld failure. Whether the UO2 loss rates through the vent tube were within acceptable limits could not be determined in view of the end-cap weld failure.

Spatial and temporal variation of freely dissolved PAHs in an urban river undergoing Superfund remediation

PubMed Central

Sower, GJ; Anderson, K.A.

2014-01-01

Urban rivers with a history of industrial use can exhibit spatial and temporal variations in contaminant concentrations that may significantly affect risk evaluations and even the assessment of remediation efforts. Concentrations of 15 biologically available priority pollutant polycyclic aromatic hydrocarbons (PAHs) were measured over five years along 18.5 miles of the lower Willamette River using passive sampling devices and HPLC. The study area includes the Portland Harbor Superfund megasite with several PAH sources including remediation operations for coal tar at RM 6.3 west and an additional Superfund site, McCormick and Baxter, at RM 7 east consisting largely of creosote contamination. Study results show that organoclay capping at the McCormick and Baxter Superfund Site reduced PAHs from a pre-cap average of 440 ± 422 ng/L to 8 ± 3 ng/L post-capping. Results also reveal that dredging of submerged coal tar nearly tripled nearby freely dissolved PAH concentrations. For apportioning sources, fluoranthene/ pyrene and phenanthrene/anthracene diagnostic ratios from passive sampling devices were established for creosote and coal tar contamination and compared to published sediment values. PMID:19174872

Initial studies using the RatCAP conscious animal PET tomograph

NASA Astrophysics Data System (ADS)

Woody, C.; Vaska, P.; Schlyer, D.; Pratte, J.-F.; Junnarkar, S.; Park, S.-J.; Stoll, S.; Purschke, M.; Southekal, S.; Kriplani, A.; Krishnamoorthy, S.; Maramraju, S.; Lee, D.; Schiffer, W.; Dewey, S.; Neill, J.; Kandasamy, A.; O'Connor, P.; Radeka, V.; Fontaine, R.; Lecomte, R.

2007-02-01

The RatCAP is a small, head-mounted PET tomograph designed to image the brain of a conscious rat without the use of anesthesia. The detector is a complete, high-performance 3D tomograph consisting of a 3.8 cm inside-diameter ring containing 12 block detectors, each of which is comprised of a 4×8 array of 2.2×2.2×5 mm 3 LSO crystals readout with a matching APD array and custom ASIC, and has a 1.8 cm axial field of view. Construction of the first working prototype detector has been completed and its performance characteristics have been measured. The results show an intrinsic spatial resolution of 2.1 mm, a time resolution of ˜14 ns FWHM, and a sensitivity of 0.7% at an energy threshold of 150 keV. First preliminary images have been obtained using 18F-FDG and 11C-methamphetamine, which show comparable image quality to those obtained from a commercial MicroPET R4 scanner. Initial studies have also been carried out to study stress levels in rats wearing the RatCAP.

Martian Radiative Transfer Modeling Using the Optimal Spectral Sampling Method

NASA Technical Reports Server (NTRS)

Eluszkiewicz, J.; Cady-Pereira, K.; Uymin, G.; Moncet, J.-L.

2005-01-01

The large volume of existing and planned infrared observations of Mars have prompted the development of a new martian radiative transfer model that could be used in the retrievals of atmospheric and surface properties. The model is based on the Optimal Spectral Sampling (OSS) method [1]. The method is a fast and accurate monochromatic technique applicable to a wide range of remote sensing platforms (from microwave to UV) and was originally developed for the real-time processing of infrared and microwave data acquired by instruments aboard the satellites forming part of the next-generation global weather satellite system NPOESS (National Polarorbiting Operational Satellite System) [2]. As part of our on-going research related to the radiative properties of the martian polar caps, we have begun the development of a martian OSS model with the goal of using it to perform self-consistent atmospheric corrections necessary to retrieve caps emissivity from the Thermal Emission Spectrometer (TES) spectra. While the caps will provide the initial focus area for applying the new model, it is hoped that the model will be of interest to the wider Mars remote sensing community.

A study on the quality control of slow burning polyester

NASA Astrophysics Data System (ADS)

Chen, Bin; Wang, Yinglei; Yan, Zhengfeng; Yu, Tao

2018-04-01

In this paper, the influence of the alcohol/acid mole ratio, reaction temperature, warm-up mode, end-capping, vacuity to the quality of slow burning polyester was studied. The hydroxyl value will increase when the alcohol/acid mole ratio increase, but the acid value and molecular weight will decrease. The molecular weight and molecular weight distribution of the polyester consistent with the designed one can be obtained by stepped heating up. Monobasic alcohol end-capping can be used to control the molecular weight effectively and reduce acid value. Stripping process narrow the molecular weight distribution and reduce the hydroxyl value. Decompression is in favor of the decrease of acid value and increase of the reaction speed to get qualified production.

Optimized capping layers for EUV multilayers

DOEpatents

Bajt, Sasa [Livermore, CA; Folta, James A [Livermore, CA; Spiller, Eberhard A [Livermore, CA

2004-08-24

A new capping multilayer structure for EUV-reflective Mo/Si multilayers consists of two layers: A top layer that protects the multilayer structure from the environment and a bottom layer that acts as a diffusion barrier between the top layer and the structure beneath. One embodiment combines a first layer of Ru with a second layer of B.sub.4 C. Another embodiment combines a first layer of Ru with a second layer of Mo. These embodiments have the additional advantage that the reflectivity is also enhanced. Ru has the best oxidation resistance of all materials investigated so far. B.sub.4 C is an excellent barrier against silicide formation while the silicide layer formed at the Si boundary is well controlled.

Burden of hospitalized childhood community-acquired pneumonia: A retrospective cross-sectional study in Vietnam, Malaysia, Indonesia and the Republic of Korea

PubMed Central

Tan, Kah Kee; Dang, Duc Anh; Kim, Ki Hwan; Kartasasmita, Cissy; Zhang, Xu-Hao; Shafi, Fakrudeen; Yu, Ta-Wen; Ledesma, Emilio; Meyer, Nadia

2018-01-01

ABSTRACT Background: Few studies describe the community-acquired pneumonia (CAP) burden in children in Asia. We estimated the proportion of all CAP hospitalizations in children from nine hospitals across the Republic of Korea (high-income), Indonesia, Malaysia (middle-income), and Vietnam (low/middle-income). Methods: Over a one or two-year period, children <5 years hospitalized with CAP were identified using ICD-10 discharge codes. Cases were matched to standardized definitions of suspected (S-CAP), confirmed (C-CAP), or bacterial CAP (B-CAP) used in a pneumococcal conjugate vaccine efficacy study (COMPAS). Median total direct medical costs of CAP-related hospitalizations were calculated. Results: Vietnam (three centers): 7591 CAP episodes were identified with 4.3% (95% confidence interval 4.2;4.4) S-CAP, 3.3% (3.2;3.4) C-CAP and 1.4% (1.3;1.4) B-CAP episodes of all-cause hospitalization in children aged <5 years. The B-CAP case fatality rate (CFR) was 1.3%. Malaysia (two centers): 1027 CAP episodes were identified with 2.7% (2.6;2.9); 2.6% (2.4;2.8); 0.04% (0.04;0.1) due to S-CAP, C-CAP, and B-CAP, respectively. One child with B-CAP died. Indonesia (one center): 960 CAP episodes identified with 18.0% (17.0;19.1); 16.8% (15.8;17.9); 0.3% (0.2;0.4) due to S-CAP, C-CAP, and B-CAP, respectively. The B-CAP CFR was 20%. Korea (three centers): 3151 CAP episodes were identified with 21.1% (20.4;21.7); 11.8% (11.2;12.3); 2.4% (2.1;2.7) due to S-CAP, C-CAP, and B-CAP, respectively. There were no deaths. Costs: CAP-related hospitalization costs were highest for B-CAP episodes: 145.00 (Vietnam) to 1013.3 USD (Korea) per episode. Conclusion: CAP hospitalization causes an important health and cost burden in all four countries studied (NMRR-12-50-10793). PMID:29125809

Cold atmospheric plasma (CAP), a novel physicochemical source, induces neural differentiation through cross-talk between the specific RONS cascade and Trk/Ras/ERK signaling pathway.

PubMed

Jang, Ja-Young; Hong, Young June; Lim, Junsup; Choi, Jin Sung; Choi, Eun Ha; Kang, Seongman; Rhim, Hyangshuk

2018-02-01

Plasma, formed by ionization of gas molecules or atoms, is the most abundant form of matter and consists of highly reactive physicochemical species. In the physics and chemistry fields, plasma has been extensively studied; however, the exact action mechanisms of plasma on biological systems, including cells and humans, are not well known. Recent evidence suggests that cold atmospheric plasma (CAP), which refers to plasma used in the biomedical field, may regulate diverse cellular processes, including neural differentiation. However, the mechanism by which these physicochemical signals, elicited by reactive oxygen and nitrogen species (RONS), are transmitted to biological system remains elusive. In this study, we elucidated the physicochemical and biological (PCB) connection between the CAP cascade and Trk/Ras/ERK signaling pathway, which resulted in neural differentiation. Excited atomic oxygen in the plasma phase led to the formation of RONS in the PCB network, which then interacted with reactive atoms in the extracellular liquid phase to form nitric oxide (NO). Production of large amounts of superoxide radical (O 2 - ) in the mitochondria of cells exposed to CAP demonstrated that extracellular NO induced the reversible inhibition of mitochondrial complex IV. We also demonstrated that cytosolic hydrogen peroxide, formed by O 2 - dismutation, act as an intracellular messenger to specifically activate the Trk/Ras/ERK signaling pathway. This study is the first to elucidate the mechanism linking physicochemical signals from the CAP cascade to the intracellular neural differentiation signaling pathway, providing physical, chemical and biological insights into the development of therapeutic techniques to treat neurological diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tobacco use and outcome in radical prostatectomy patients.

PubMed

Curtis, Alexandra; Ondracek, Rochelle Payne; Murekeyisoni, Christine; Kauffman, Eric; Mohler, James; Marshall, James

2017-04-01

Cigarette smoking has been consistently associated with increased risk of overall mortality, but the importance of smoking for patients with prostate cancer (CaP) who are candidates for curative radical prostatectomy (RP) has received less attention. This retrospectively designed cohort study investigated the association of smoking history at RP with subsequent CaP treatment outcomes and overall mortality. A total of 1981 patients who underwent RP at Roswell Park Cancer Institute (RPCI) between 1993 and 2014 were studied. Smoking history was considered as a risk factor for overall mortality as well as for currently accepted CaP treatment outcomes (biochemical failure, treatment failure, distant metastasis, and disease-specific mortality). The associations of smoking status with these outcomes were tested by Cox proportional hazard analyses. A total of 153 (8%) patients died during follow-up. Current smoking at diagnosis was a statistically significant predictor of overall mortality after RP (current smokers vs. former and never smokers, hazards ratio 2.07, 95% confidence interval [CI]: 1.36-3.14). This association persisted for overall mortality at 3, 5, and 10 years (odds ratios 2.07 [95% CI: 1.36-3.15], 2.05 [95% CI: 1.35-3.12], and 1.8 [95% CI: 1.18-2.74], respectively). Smoking was not associated with biochemical failure, treatment failure, distant metastasis, or CaP-specific mortality, and the association of smoking with overall mortality did not appear to be functionally related to treatment or biochemical failure, or to distant metastasis. Smoking is a non-negligible risk factor for death among CaP patients who undergo RP; patients who smoke are far more likely to die of causes other than CaP. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Targets for antibiotic and healthcare resource stewardship in inpatient community-acquired pneumonia: a comparison of management practices with National Guideline Recommendations.

PubMed

Jenkins, T C; Stella, S A; Cervantes, L; Knepper, B C; Sabel, A L; Price, C S; Shockley, L; Hanley, M E; Mehler, P S; Burman, W J

2013-02-01

Community-acquired pneumonia (CAP) is the most common infection leading to hospitalization in the USA. The objective of this study was to evaluate management practices for inpatient CAP in relation to Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) guidelines to identify opportunities for antibiotic and health care resource stewardship. This was a retrospective cohort study of adults hospitalized for CAP at a single institution from 15 April 2008 to 31 May 2009. Of the 209 patients with CAP who presented to Denver Health Medical Center during the study period and were hospitalized, 166 (79 %) and 43 (21 %) were admitted to a medical ward and the intensive care unit (ICU), respectively. Sixty-one (29 %) patients were candidates for outpatient therapy per IDSA/ATS guidance with a CURB-65 score of 0 or 1 and absence of hypoxemia. Sputum cultures were ordered for 110 specimens; however, an evaluable sample was obtained in only 49 (45 %) cases. Median time from antibiotic initiation to specimen collection was 11 [interquartile range (IQR) 6-19] h, and a potential pathogen was identified in only 18 (16 %) cultures. Blood cultures were routinely obtained for both non-ICU (81 %) and ICU (95 %) cases, but 15 of 36 (42 %) positive cultures were false-positive results. The most common antibiotic regimen was ceftriaxone + azithromycin (182, 87 % cases). Discordant with IDSA/ATS recommendations, oral step-down therapy consisted of a new antibiotic class in 120 (66 %), most commonly levofloxacin (101, 55 %). Treatment durations were typically longer than suggested with a median of 10 (IQR 8-12) days. In this cohort of patients hospitalized for CAP, management was frequently inconsistent with IDSA/ATS guideline recommendations, revealing potential targets to reduce unnecessary antibiotic and healthcare resource utilization.

Canakinumab in patients with cryopyrin-associated periodic syndrome: an update for clinicians

PubMed Central

Haug, Iris

2013-01-01

The cryopyrin-associated periodic syndrome (CAPS) is a very rare disease. It is estimated that there are 1–2 cases for every 1 million people in the US and 1 in every 360,000 in France. However, many patients are diagnosed very late or not at all, meaning the real prevalence is likely to be higher. CAPS encompasses the three entities of familial cold auto-inflammatory syndrome (FCAS), Muckle–Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID)/chronic infantile neurologic, cutaneous and articular (CINCA) syndrome. They have in common a causative mutation in the NLRP3 gene. The altered gene product cryopyrin leads to activation of the inflammasome which in turn is responsible for excessive production of interleukin (IL)-1β. IL-1β causes the inflammatory manifestations in CAPS. These appear as systemic inflammation including fever, headache or fatigue, rash, eye disease, progressive sensorineural hearing loss, musculoskeletal manifestations and central nervous system (CNS) symptoms (NOMID/CINCA only). With the advent of IL-1 Inhibitors, safe and effective therapeutic options became available for this devastating disease. To prevent severe and possible life-threatening disease sequelae, early and correct diagnosis and immediate initiation of therapy are mandatory in most patients. Canakinumab is a fully human monoclonal IgG1 anti-IL-1β antibody. It provides selective and prolonged IL-1β blockade and has demonstrated a rapid (within hours), complete and sustained response in most CAPS patients without any consistent pattern of side effects. Long-term follow-up trials have demonstrated sustained efficacy, safety and tolerability. Canakinumab is approved by the US Food and Drug Administration for FCAS and MWS and by European Medicines Agency for treatment of all three phenotypes of CAPS. PMID:24294305

An association between central aortic pressure and subclinical organ damage of the heart among a general Japanese cohort: Circulatory Risk in Communities Study (CIRCS).

PubMed

Cui, Renzhe; Li, Yuanying; Krisztina, Gero; Yamagishi, Kazumasa; Umesawa, Mitsumasa; Imano, Hironori; Ohira, Tetsuya; Kiyama, Masahiko; Okada, Takeo; Kitamura, Akihiko; Hitsumoto, Shinichi; Tanigawa, Takeshi; Iso, Hiroyasu

2014-01-01

This study aimed to investigate associations between central aortic pressure (CAP) and subclinical organ damage of the heart amongst the general population. We conducted a cross-sectional study in a community-based population, consisting of 3002 men and women aged between 40 and 79 years. The CAP was measured using the HEM-9000AI device, an automated tonometer. Electrocardiograms (ECG) were read according to the Minnesota Code. Subclinical organ damage in the heart was defined as measurable left high amplitude R waves (LHAR), major and minor ST-T abnormalities, and left ventricular hypertrophy (LVH). Age- and sex-adjusted prevalence of LHAR, major and minor ST-T abnormalities, and LVH was higher for subjects in the highest tertile of CAP levels than those in the lowest tertile. After further adjustments for other cardiovascular risk factors, these associations did not change substantially. The multivariable odds ratios (ORs) (95% CI) of LHAR, major and minor ST-T abnormalities, and LVH for the highest tertile of CAP levels compared to the lowest tertile were 2.7(1.9-3.9), 1.8(1.1-2.9), 1.7(1.3-2.3) and 3.2(1.3-8.1), respectively. The positive associations with LHAR and minor ST-T abnormalities were observed primarily among non-hypertensive subjects. The respective corresponding ORs were 2.8(1.7-4.6) and 1.7(1.2-2.4) for non-hypertensive subjects, and 1.7(0.9-3.3) and 1.1(0.7-1.8) for hypertensive subjects. CAP levels were associated with subclinical organ damage of the heart independent of cardiovascular risk factors, and these associations were primarily seen in non-hypertensive subjects. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Application of the revised WHO causality assessment protocol for adverse events following immunization in India.

PubMed

Singh, Awnish Kumar; Wagner, Abram L; Joshi, Jyoti; Carlson, Bradley F; Aneja, Satinder; Boulton, Matthew L

2017-07-24

In 2013, the World Health Organization (WHO) and CIOMS introduced a revised Causality Assessment Protocol (CAP) for Adverse Events following Immunization (AEFI). India is one of the first countries to adopt the revised CAP. This study describes the application of the revised CAP in India. We describe use of CAP by India's AEFI surveillance program to assess reported AEFIs. Using publicly available results of causality assessment for reported AEFIs, we describe the results by demographic characteristics and review the trends for the results of the causality assessment. A total of 771 reports of AEFI between January 2012 and January 2015, completed causality review by August 2016. The cases were reported as belonging to a cluster (54%; n=302), hospitalized or requiring hospitalization (41%; n=270), death (25%; n=195), or resulting in disability (0.4%; n=3). The most common combinations of vaccines leading to report of an AEFI were DTwP, Hepatitis B, and OPV (14%; n=106), followed by Pentavalent and OPV (13%; n=103), and JE vaccine (13%; n=101). Using the WHO Algorithm, most AEFI reports (89%, n=683) were classifiable. Classifiable AEFI reports included those with a consistent causal association (53%; n=407), an inconsistent causal association (29%; n=226) or were indeterminate causal association with implicated vaccine(s) or vaccination process (6.5%; n=50) (Fig. 1); 88 reports remained unclassifiable. The revised CAP was informative and useful in classifying most of the reviewed AEFIs in India. Unclassifiable reports could be minimized with more complete information from health records. Improvements in causality assessment, and standardization in reporting between countries, can improve public confidence in vaccine system performance and identify important vaccine safety signals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lack of independent significance of a close (<1 mm) circumferential resection margin involvement in esophageal and junctional cancer.

PubMed

O'Farrell, N J; Donohoe, C L; Muldoon, C; Costelloe, J M; King, S; Ravi, N; Reynolds, J V

2013-08-01

For rectal cancer, an involved circumferential resection margin (CRM), defined as tumor cells within 1 mm of the CRM, is of established prognostic significance. This definition for the esophagus, however, is controversial, with the UK Royal College of Pathologists (RCP) recommending the 1 mm definition, while the College of American Pathologists (CAP) advises that only tumor cells at the cut margin (0 mm) define an incomplete (R1) resection. The aim of this study was to compare the clinical significance of both definitions in patients with pT3 tumors. CAP- and RCP-defined CRM status in patients treated by surgery only or by multimodal therapy was recorded prospectively in a comprehensive database from May 2003 to May 2011. Kaplan-Meier survival curves were generated, and factors affecting survival were assessed by univariate and multivariate analysis. A total of 157 of 340 patients had pT3 esophageal tumors, with RCP-positive CRM in 60 %, and 18 % by CAP. There were no significant differences between RCP-positive CRM and negative margins for node-positive disease, local recurrence, and survival. CAP-positive CRM was associated with positive nodes (P = 0.036) and poorer survival (P = 0.023). Multivariate analysis revealed nodal invasion to be the only independent prognostic variable (P = 0.004). A CRM margin of <1 mm is common in pT3 esophageal tumors, a finding consistent with other reports. The <1 mm definition was not associated with node positivity, local recurrence, or survival, in contrast to actual involvement at the margin, suggesting lack of independent prognostic significance of the RCP definition and possible superiority of the CAP criteria for prospective registration of CRM.

Insulin sensitizers prevent fine particulate matter-induced vascular insulin resistance and changes in endothelial progenitor cell homeostasis.

PubMed

Haberzettl, Petra; McCracken, James P; Bhatnagar, Aruni; Conklin, Daniel J

2016-06-01

Exposure to fine particular matter (PM2.5) increases the risk of developing cardiovascular disease and Type 2 diabetes. Because blood vessels are sensitive targets of air pollutant exposure, we examined the effects of concentrated ambient PM2.5 (CAP) on vascular insulin sensitivity and circulating levels of endothelial progenitor cells (EPCs), which reflect cardiovascular health. We found that CAP exposure for 9 days decreased insulin-stimulated Akt phosphorylation in the aorta of mice maintained on control diet. This change was accompanied by the induction of IL-1β and increases in the abundance of cleaved IL-18 and p10 subunit of Casp-1, consistent with the activation of the inflammasome pathway. CAP exposure also suppressed circulating levels of EPCs (Flk-1(+)/Sca-1(+) cells), while enhancing the bone marrow abundance of these cells. Although similar changes in vascular insulin signaling and EPC levels were observed in mice fed high-fat diet, CAP exposure did not exacerbate diet-induced changes in vascular insulin resistance or EPC homeostasis. Treatment with an insulin sensitizer, metformin or rosiglitazone, prevented CAP-induced vascular insulin resistance and NF-κB and inflammasome activation and restored peripheral blood and bone marrow EPC levels. These findings suggest that PM2.5 exposure induces diet-independent vascular insulin resistance and inflammation and prevents EPC mobilization, and that this EPC mobilization defect could be mediated by vascular insulin resistance. Impaired vascular insulin sensitivity may be an important mechanism underlying PM2.5-induced vascular injury, and pharmacological sensitization to insulin action could potentially prevent deficits in vascular repair and mitigate vascular inflammation due to exposure to elevated levels of ambient air pollution. Copyright © 2016 the American Physiological Society.

Insulin sensitizers prevent fine particulate matter-induced vascular insulin resistance and changes in endothelial progenitor cell homeostasis

PubMed Central

McCracken, James P.; Bhatnagar, Aruni; Conklin, Daniel J.

2016-01-01

Exposure to fine particular matter (PM2.5) increases the risk of developing cardiovascular disease and Type 2 diabetes. Because blood vessels are sensitive targets of air pollutant exposure, we examined the effects of concentrated ambient PM2.5 (CAP) on vascular insulin sensitivity and circulating levels of endothelial progenitor cells (EPCs), which reflect cardiovascular health. We found that CAP exposure for 9 days decreased insulin-stimulated Akt phosphorylation in the aorta of mice maintained on control diet. This change was accompanied by the induction of IL-1β and increases in the abundance of cleaved IL-18 and p10 subunit of Casp-1, consistent with the activation of the inflammasome pathway. CAP exposure also suppressed circulating levels of EPCs (Flk-1+/Sca-1+ cells), while enhancing the bone marrow abundance of these cells. Although similar changes in vascular insulin signaling and EPC levels were observed in mice fed high-fat diet, CAP exposure did not exacerbate diet-induced changes in vascular insulin resistance or EPC homeostasis. Treatment with an insulin sensitizer, metformin or rosiglitazone, prevented CAP-induced vascular insulin resistance and NF-κB and inflammasome activation and restored peripheral blood and bone marrow EPC levels. These findings suggest that PM2.5 exposure induces diet-independent vascular insulin resistance and inflammation and prevents EPC mobilization, and that this EPC mobilization defect could be mediated by vascular insulin resistance. Impaired vascular insulin sensitivity may be an important mechanism underlying PM2.5-induced vascular injury, and pharmacological sensitization to insulin action could potentially prevent deficits in vascular repair and mitigate vascular inflammation due to exposure to elevated levels of ambient air pollution. Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/particulate-matter-induced-vascular-insulin-resistance/. PMID:27016579

Strong IMF By-Related Plasma Convection in the Ionosphere and Cusp Field-Aligned Currents Under Northward IMF Conditions

NASA Technical Reports Server (NTRS)

Le, G.; Lu, G.; Strangeway, R. J.; Pfaff, R. F., Jr.; Vondrak, Richard R. (Technical Monitor)

2001-01-01

We present in this paper an investigation of IMF-By related plasma convection and cusp field-aligned currents using FAST data and AMIE model during a prolonged interval with large positive IMF By and northward Bz conditions (By/Bz much greater than 1). Using the FAST single trajectory observations to validate the global convection patterns at key times and key locations, we have demonstrated that the AMIE procedure provides a reasonably good description of plasma circulations in the ionosphere during this interval. Our results show that the plasma convection in the ionosphere is consistent with the anti-parallel merging model. When the IMF has a strongly positive By component under northward conditions, we find that the global plasma convection forms two cells oriented nearly along the Sun-earth line in the ionosphere. In the northern hemisphere, the dayside cell has clockwise convection mainly circulating within the polar cap on open field lines. A second cell with counterclockwise convection is located in the nightside circulating across the polar cap boundary, The observed two-cell convection pattern appears to be driven by the reconnection along the anti-parallel merging lines poleward of the cusp extending toward the dusk side when IMF By/Bz much greater than 1. The magnetic tension force on the newly reconnected field lines drives the plasma to move from dusk to dawn in the polar cusp region near the polar cap boundary. The field-aligned currents in the cusp region flow downward into the ionosphere. The return field-aligned currents extend into the polar cap in the center of the dayside convection cell. The field-aligned currents are closed through the Peterson currents in the ionosphere, which flow poleward from the polar cap boundary along the electric field direction.

Quantification of octacalcium phosphate, authigenic apatite and detrital apatite in coastal sediments using differential dissolution and standard addition

NASA Astrophysics Data System (ADS)

Oxmann, J. F.; Schwendenmann, L.

2014-06-01

Knowledge of calcium phosphate (Ca-P) solubility is crucial for understanding temporal and spatial variations of phosphorus (P) concentrations in water bodies and sedimentary reservoirs. In situ relationships between liquid- and solid-phase levels cannot be fully explained by dissolved analytes alone and need to be verified by determining particular sediment P species. Lack of quantification methods for these species limits the knowledge of the P cycle. To address this issue, we (i) optimized a specifically developed conversion-extraction (CONVEX) method for P species quantification using standard additions, and (ii) simultaneously determined solubilities of Ca-P standards by measuring their pH-dependent contents in the sediment matrix. Ca-P minerals including various carbonate fluorapatite (CFAP) specimens from different localities, fluorapatite (FAP), fish bone apatite, synthetic hydroxylapatite (HAP) and octacalcium phosphate (OCP) were characterized by XRD, Raman, FTIR and elemental analysis. Sediment samples were incubated with and without these reference minerals and then sequentially extracted to quantify Ca-P species by their differential dissolution at pH values between 3 and 8. The quantification of solid-phase phosphates at varying pH revealed solubilities in the following order: OCP > HAP > CFAP (4.5% CO3) > CFAP (3.4% CO3) > CFAP (2.2% CO3) > FAP. Thus, CFAP was less soluble in sediment than HAP, and CFAP solubility increased with carbonate content. Unspiked sediment analyses together with standard addition analyses indicated consistent differential dissolution of natural sediment species vs. added reference species and therefore verified the applicability of the CONVEX method in separately determining the most prevalent Ca-P minerals. We found surprisingly high OCP contents in the coastal sediments analyzed, which supports the hypothesis of apatite formation by an OCP precursor mechanism.

Quantification of octacalcium phosphate, authigenic apatite and detrital apatite in coastal sediments using differential dissolution and standard addition

NASA Astrophysics Data System (ADS)

Oxmann, J. F.; Schwendenmann, L.

2014-01-01

Knowledge of calcium phosphate (Ca-P) solubility is crucial for understanding temporal and spatial variations of phosphorus (P) concentrations in water bodies and sedimentary reservoirs. In-situ relationships between liquid and solid-phase levels cannot be fully explained by dissolved analytes alone and need to be verified by determination of particular sediment P species. Lack of quantification methods for these species limits the knowledge of the P cycle. To address this issue, we (i) optimized a specifically developed conversion-extraction (CONVEX) method for P species quantification using standard additions; and (ii) simultaneously determined solubilities of Ca-P standards by measuring their pH-dependent contents in the sediment matrix. Ca-P minerals including various carbonate fluorapatite (CFAP) specimens from different localities, fluorapatite (FAP), fish bone apatite, synthetic hydroxylapatite (HAP) and octacalcium phosphate (OCP) were characterized by XRD, Raman, FTIR and elemental analysis. Sediment samples were incubated with and without these reference minerals and then sequentially extracted to quantify Ca-P species by their differential dissolution at pH values between 3 and 8. The quantification of solid-phase phosphates at varying pH revealed solubilities in the following order: OCP > HAP > CFAP (4.5% CO3) > CFAP (3.4% CO3) > CFAP (2.2% CO3) > FAP. Thus, CFAP was less soluble in sediment than HAP, and CFAP solubility increased with carbonate content. Unspiked sediment analyses together with standard addition analyses indicated consistent differential dissolution of natural sediment species vs. added reference species and therefore verified the applicability of the CONVEX method in separately determining the most prevalent Ca-P minerals. We found surprisingly high OCP contents in the analyzed coastal sediments which supports the hypothesis of apatite formation by an OCP precursor.

Parental Depression and Pancreatic Enzymes Adherence in Children With Cystic Fibrosis.

PubMed

Barker, David H; Quittner, Alexandra L

2016-02-01

Treatment adherence in cystic fibrosis (CF) is often poor, however, less is known about adherence to pancreatic enzymes, a critical component of the CF treatment regimen. Parent caregivers often report elevations in depression, and parental depression may adversely affect children's adherence. This prospective study evaluated adherence to pancreatic enzymes in 83 patients (1-13 years) . Adherence was measured across 3 months with electronic pill-caps . Weight was measured at baseline and a 3-month follow-up. Parental depressive symptoms were evaluated by using the Center for Epidemiologic Studies Depression Scale (CES-D). Adherence to pancreatic enzymes was 49.4% ± 3.4%. Adherence was higher at school (94.4% ± 6.1%) than at home (42.3% ± 3.1%), and higher for toddlers (50.6% ± 5.2%) than for school-aged children (37.5% ± 3.7%). Parents reported high rates of depressive symptoms (30% in the clinical range, 18% with moderate symptoms). Children of parents with symptoms of depression versus those without were less adherent (34.8% ± 4.5% vs 48.5% ± 4.1%), and adherence to enzymes was significantly related to 3-month weight outcomes. Average gain in weight z scores across 3 months was 0.5 ± 0.2for children who were >50% adherent and -0.1 ± 6.1for children who were <33% adherent. Parental depression had a signifcant, indirect effect on weight via adherence (-0.005 ± 0.003 gain in weight z score per CES-D unit ). High rates of parental depressive symptoms, coupled with its negative effects on adherence, suggest that measuring and treating parental depression may improve children's adherence to therapy. Copyright © 2016 by the American Academy of Pediatrics.

The Impact of Business School Students' Psychological Capital on Academic Performance

ERIC Educational Resources Information Center

Luthans, Brett Carl; Luthans, Kyle William; Jensen, Susan M.

2012-01-01

Psychological capital (PsyCap) consisting of the psychological resources of hope, efficacy, resiliency, and optimism has been empirically demonstrated in the published literature to be related to manager and employee positive organizational outcomes and to be open to development. However, to date, little attention has been devoted to the impact of…

Suspected systemic calcinosis and calciphylaxis in 5 horses

PubMed Central

Tan, Jean-Yin; Valberg, Stephanie J.; Sebastian, Manu M.; Davis, Gordon D.; Kelly, Jenny R.; Goehring, Lutz S.; Harland, Malte M.; Kuebelbeck, K. Leann; Waldridge, Bryan M.; Newton, Joseph C.; Reimer, Johanna M.

2010-01-01

Five horses were presented with signs of myopathy along with systemic malaise, hyperfibrinogenemia, hyperphosphatemia, and an elevated calcium phosphorus product (Ca*P). Postmortem findings were consistent with systemic calcinosis, a syndrome of calcium deposition in the tissue of organs including lungs, kidneys, muscle, and heart that has not been previously described in horses. PMID:21119866

75 FR 76280 - Regulated Navigation Area; Thea Foss and Wheeler-Osgood Waterways EPA Superfund Cleanup Site...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-08

.../ Tideflats superfund cleanup remediation efforts. This RNA will prohibit activities that would disturb the.../Tideflats superfund cleanup remediation process in those waters. These caps consist of approximately three... remediation efforts of the U.S. Environmental Protection Agency (EPA) and others in the Thea Foss and Wheeler...

Incipient Crack Detection in Composite Wind Turbine Blades

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

Taylor, Stuart G.; Choi, Mijin; Jeong, Hyomi

2012-08-28

This paper presents some analysis results for incipient crack detection in a 9-meter CX-100 wind turbine blade that underwent fatigue loading to failure. The blade was manufactured to standard specifications, and it underwent harmonic excitation at its first resonance using a hydraulically-actuated excitation system until reaching catastrophic failure. This work investigates the ability of an ultrasonic guided wave approach to detect incipient damage prior to the surfacing of a visible, catastrophic crack. The blade was instrumented with piezoelectric transducers, which were used in an active, pitchcatch mode with guided waves over a range of excitation frequencies. The performance results inmore » detecting incipient crack formation in the fiberglass skin of the blade is assessed over the range of frequencies in order to determine the point at which the incipient crack became detectable. Higher excitation frequencies provide consistent results for paths along the rotor blade's carbon fiber spar cap, but performance falls off with increasing excitation frequencies for paths off of the spar cap. Lower excitation frequencies provide more consistent performance across all sensor paths.« less

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

Popp, R.A.; Lalley, P.A.; Whitney, J.B.

A genetic polymorphism for a Bgl I endonuclease site near the ..cap alpha..-globin-like pseudogene ..cap alpha..-4 of C57BL/6 and C3H/HeN mice was used to show that ..cap alpha..-4 was not affected by three independent mutations in which the adult globin genes ..cap alpha..-1 and ..cap alpha..-2 were deleted. These results indicated that ..cap alpha..-4 might not be located adjacent to the adult ..cap alpha..-globin genes on chromosome 11. Restriction endonuclease analysis of DNA of a primary clone of a Chinese hamster-mouse somatic cell hybrid that had lost mouse chromosomes 11 and 18 showed that this clone lacked the adult murinemore » globin genes ..cap alpha..-1 and ..cap alpha..-2 but it did contain the ..cap alpha..-globin-like pseudogenes ..cap alpha..-3 and ..cap alpha..-4. These results indicated that the adult ..cap alpha..-globin genes and ..cap alpha..-globin-like pseudogenes are not located on the same chromosome. Similar analyses of several other Chinese hamster-mouse somatic cell hybrids that had segregated other mouse chromosomes indicated that the ..cap alpha..-globin-like pseudogenes ..cap alpha..-3 and ..cap alpha..-4 are located on mouse chromosomes 15 and 17, respectively. These data explain why ..cap alpha..-3 and ..cap alpha..-4 were not affected by the three independently induced deletion-type mutations that cause ..cap alpha..-thalassemia in the mouse.« less

78 FR 18335 - Central Arizona Project-Rate Order No. WAPA-158

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-26

... Project, reflected in Transmission Service Rate Schedules CAP-FT2, CAP-NFT2, and CAP-NITS2, from January 1... existing Rate Schedules CAP-FT2, CAP-NFT2, CAP-NITS2 under Rate Order No. WAPA-124,\\1\\ were approved for a... Transmission Service Rate Schedules CAP-FT2, CAP-NFT2, and CAP-NITS2 on an interim basis effective as of...

Effects of dietary addition of capsicum extract on intake, water consumption, and rumen fermentation of fattening heifers fed a high-concentrate diet.

PubMed

Rodríguez-Prado, M; Ferret, A; Zwieten, J; Gonzalez, L; Bravo, D; Calsamiglia, S

2012-06-01

Four beef Holstein heifers (BW = 438 ± 71 kg) fitted with a 1-cm i.d. plastic ruminal trocars were used in a 4 × 4 Latin square design to evaluate the effect of 3 doses of capsicum extract (CAP) on intake, water consumption, and ruminal fermentation in heifers fed a high-concentrate diet. Animals were fed (DM basis) 10% barley straw and 90% concentrate (32.2% barley grain, 27.9% ground corn, 7.5% wheat bran, 10.7% soybean meal, 10.7% soybean hulls, 7.2% corn gluten feed, 3.1% mineral-vitamin mix; 16.6% CP, 18.3% NDF). Treatments were no additive (CTR), 125 (CAP125), 250 (CAP250), and 500 (CAP500) mg/d of capsicum oleoresin standardized with 6% of capsaicin and dihydrocapsaicin (XTract 6933, Pancosma, Geneva, Switzerland). Each experimental period consisted of 25 d (15 d for adaptation, 5 d of continuous measurement of DMI, and 3 d for rumen sample collection). Animals had ad libitum access to water and feed offered once daily at 0800 h. Data were analyzed by the MIXED procedure of SAS. The model included the fixed effects of period and treatment, the random effect of heifer, and the residual error. The effects were tested for linear and quadratic effects. A linear response was observed (CTR, CAP125, CAP250, and CAP500, respectively) for DMI (8.56, 9.84, 8.68, and 9.40 kg/d; P < 0.04), ruminal pH (6.03, 5.84, 5.96, and 5.86; P < 0.08) and total VFA (134.3, 144.8, 140.1, and 142.8 mM; P < 0.08). There was a strong correlation between water consumption and DMI (R(2) = 0.98). Dry matter intake in the first 2 h after feeding was reduced (P < 0.05) in all CAP treatments compared with control. The molar proportion of acetate tended to decrease linearly (from 59.6 to 55.5 mol/100 mol; P < 0.06), and ammonia N concentration tended to increase linearly (from 14.4 to 16.0 mg N/dL; P < 0.08). In contrast, the molar proportion of propionate (23.8 mol/100 mol), butyrate (14.2 mol/100 mol), and lactate (0.28 mol/100 mol) were not affected by treatments. Results indicate that capsicum extract stimulated DMI and modified the pattern of DMI in beef cattle fed high concentrate diets.

Cryogenian cap carbonates - what do laminar scale investigations reveal about formation?

NASA Astrophysics Data System (ADS)

Miller, N. R.; Maupin, C. R.; Partin, J. W.; Quinn, T.; Giddings, J.

2009-12-01

Mid- to Late-Neoproterozoic “Cryogenian” cap carbonates are generally regarded as marine chemical sediments rapidly deposited during climatic recoveries from some of Earth’s most extreme glacial intervals, but there is little consensus regarding formation. Many cap successions initiate abruptly above glacigenic strata as finely laminated carbonate (typically dolostone), even in otherwise siliciclastic dominated marine continua, suggesting water mass control and widespread deposition below storm wave base. Cap carbonate units often culminate intervals of ongoing negative δ13C, transitioning to positive δ13C in the higher succession. Considering that fine lamination is a common characteristic among many cap carbonate units in space and time, laminar scale chemostratigraphic investigations may offer insights to modes of formation. Toward this end, we integrate bedding-normal LA-ICP-MS scans and high-resolution C and O isotope stratigraphy, for an array of cap carbonate units spanning “Kaigas”, “Sturtian”, and “Marinoan” post-glacial intervals; namely: Assem Limestone, N. Ethiopia (Nubia); Beck Spring Dolomite and Noonday Dolomite, Death Valley Area (W. Laurentia); Scout Mountain Member of the Pocatello Formation, S. Idaho (W. Laurentia); Tindelpina Shale Member, S. Australia (Adelaide Geosyncline); Rasthof and Keilberg Formations, N. Namibia (Congo Craton); and Mirrasol O’est, Brazil (Sao Francisco Craton). Whole-rock assessments for basal cap samples have δ13C between -4.8 to -1.4‰ and δ18O between -15.5 to -3.1‰. Corresponding PASS-normalized REE patterns show moderate LREE depletion, minor MREE enrichment, and slight HREE depletion. Cap samples from the higher positive δ13C succession (Noonday/Rasthof) display flatter patterns. Laser ablation scans for the Rasthof Fm (basal rhythmite and middle sublittoral microbialite) and Noonday Dolomite show that lamina couplets consist of alternations of comparatively darker organic/terrigenous (Si, Al, Ba, Rb) and lighter carbonate (Ca, Mg, Sr, Ce) end-members. For the middle Rasthof Formation, alternating dark-light couplets show sympathetic patterns of enrichment and depletion in both δ13C and δ18O, not easily reconciled by meteoric diagenetic processes. The presence of roll-up structures and internal cements (Rasthof) argues that the locus of carbonatogenesis was at or below the sediment-water interface. Within couplet δ18O variation is ~1‰, analogous to ~5°C temperature variation in modern oceans. Distinct alternation of δ18O between couplets may thus indicate moderate changes in bottom water temperatures or that carbonatogenesis was linked to contrasting water masses.

Condensin II Resolves Chromosomal Associations to Enable Anaphase I Segregation in Drosophila Male Meiosis

PubMed Central

Hartl, Tom A.; Sweeney, Sarah J.; Knepler, Peter J.; Bosco, Giovanni

2008-01-01

Several meiotic processes ensure faithful chromosome segregation to create haploid gametes. Errors to any one of these processes can lead to zygotic aneuploidy with the potential for developmental abnormalities. During prophase I of Drosophila male meiosis, each bivalent condenses and becomes sequestered into discrete chromosome territories. Here, we demonstrate that two predicted condensin II subunits, Cap-H2 and Cap-D3, are required to promote territory formation. In mutants of either subunit, territory formation fails and chromatin is dispersed throughout the nucleus. Anaphase I is also abnormal in Cap-H2 mutants as chromatin bridges are found between segregating heterologous and homologous chromosomes. Aneuploid sperm may be generated from these defects as they occur at an elevated frequency and are genotypically consistent with anaphase I segregation defects. We propose that condensin II–mediated prophase I territory formation prevents and/or resolves heterologous chromosomal associations to alleviate their potential interference in anaphase I segregation. Furthermore, condensin II–catalyzed prophase I chromosome condensation may be necessary to resolve associations between paired homologous chromosomes of each bivalent. These persistent chromosome associations likely consist of DNA entanglements, but may be more specific as anaphase I bridging was rescued by mutations in the homolog conjunction factor teflon. We propose that the consequence of condensin II mutations is a failure to resolve heterologous and homologous associations mediated by entangled DNA and/or homolog conjunction factors. Furthermore, persistence of homologous and heterologous interchromosomal associations lead to anaphase I chromatin bridging and the generation of aneuploid gametes. PMID:18927632

Host-pathogen interactions. XXIX. Oligogalacturonides released from sodium polypectate by endopolygalacturonic acid lyase are elicitors of phytoalexins in soybean. [Glycine max L

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

Davis, K.R.; Darvill, A.G.; Albersheim, P.

1986-02-01

Recent studies have demonstrated that an apparently homogeneous preparation of an ..cap alpha..-1,4-D-endopolygalacturonic acid lyase (EC 4.2,2.2) isolated from the phytopathogenic bacterium Erwinia carotovora induced phytoalexin accumulation in cotyledons of soybean (Glycine max (L.) Merr. cv Wayne) and that this pectin-degrading enzyme released heat-stable elicitors of phytoalexins from soybean cell walls, citrus pectin, and sodium polypectate. The present paper reports the purification, by anion-exchange chromatography on QAE-Sephadex columns followed by gel-permeation chromatography on a Bio-Gel P-6 column, of the two fractions with highest specific elicitor activity present in a crude elicitor-preparation obtained by lyase treatment of sodium polypectate. Structural analysismore » of the fraction with highest specific elicitor activity indicated that the major, if not only, component was a decasaccharide of ..cap alpha..-1,4-D-galactosyluronic acid that contained the expected product of lyase cleavage, 4-deoxy-..beta..-L-5-threo-hexopyranos-4-enyluronic acid (4,5-unsaturated galactosyluronic acid), at the nonreducing terminus. This modified decagalacturonide fraction exhibited half-maximum and maximum elicitor activity at 1 microgram/cotyledon (6 micromolar) and 5 micrograms/cotyledon (32 micromolar) galactosyluronic acid equivalents, respectively. Reducing 90 to 95% of the carboxyl groups of the galactosyluronic acid residues abolished the elicitor activity of the decagalacturonide fraction. The second most elicitor-active fraction contained mostly undeca-..cap alpha..-1,4-D-galactosyluronic acid that contained 4,5-unsaturated galactosyluronic acid at the nonreducing termini. This fraction exhibited half-maximum and maximum elicitor activity at approximately 3 micrograms/cotyledon (17 micromolar) and 6 micrograms/cotyledon (34 micromolar) galactosyluronic acid equivalents, respectively.« less

Inhibition of metabolism and DNA binding of polycyclic aromatic hydrocarbons (PAHs) by plant phenols in epidermis of SENCAR mice

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

Das, M.; Bik, D.P.; Bickers, D.R.

1986-03-05

Naturally occurring plant phenols such as tannic acid (TA), quercetin (QT), myricetin (MY) and anthraflavic acid (AA) have been shown to inhibit the mutagenicity of several bay-region diolepoxides of PAHs. Since skin is a target for PAH carcinogenesis, they investigated the effect of these plant phenols on epidermal aryl hydrocarbon hydroxylase (AHH) activity and the binding of PAHs to DNA in SENCAR mice. Each of the plant phenols tested was found to be an in vitro and in vivo inhibitor of epidermal AHH activity with I/sub 50/ values ranging from 4.4 x 10/sup -5/ - 12.4 x 10/sup -5/M inmore » control and 3-methylcholanthrene (MCA) pretreated skin. On an equimolar basis TA was the most potent inhibitor with a Ki of 81 ..mu..M. Incubation of TA, QT, MY and AA with epidermal microsomes resulted in varying degrees of inhibition of enzyme mediated covalent binding of benzo(a)pyrene (BP) to calf thymus DNA. TA (25 ..mu..M) showed maximum inhibition (64%). A single topical application (12 ..mu..mol) of TA, QT, MY and AA resulted in significant decrease in the binding of BP, BP-7,8-diol and 7,12-dimethylbenz(a)anthracene to epidermal DNA. The formation of (+)-7..beta..,8..cap alpha..-dihydroxy-9..cap alpha..,10..cap alpha..-epoxy-7,8,9,10-tetrahydro-BP-deoxyguanine adduct in epidermis was significantly reduced (62-86%) following topical application of the plant phenols. Their results suggest that some of these plant phenols have substantial though variable potential to modify the risk of PAHs induced skin carcinogenicity.« less

Some Biochemical Properties of an Acido-Thermophilic Archae-Bacterium Sulfolobus Acidocaldarius

NASA Astrophysics Data System (ADS)

Oshima, Tairo; Ohba, Masayuki; Wagaki, Takayoshi

1984-12-01

To elucidate the phylogenic status of archaebacteria, some basic cellular components of an acido-thermophilic archaebacterium,Sulfolobus acidocaldarius, were studied. Poly(A) containing RNA was present in the cells, and performed the role of mRNA in a cell-free extract of reticulocyte or the archaebacteria. Poly(A) containing RNA was also found in other archaebacterial cells. The absence of cap structure was suggested in these RNAs. The cell-free protein synthesis using the archaebacterial extract was inhibited by anisomycin, a specific inhibitor for eukaryotic ribosomes. Two unique membrane-bound ATPases were detected. Based on resistance to H+-ATPase inhibitors, these enzymes seemed not to be F0F1-ATPase.

Investigating Viruses during the Transformation of Molecular Biology.

PubMed

Moss, Bernard

2017-03-10

This Reflections article describes my early work on viral enzymes and the discovery of mRNA capping, how my training in medicine and biochemistry merged as I evolved into a virologist, the development of viruses as vaccine vectors, and how scientific and technological developments during the 1970s and beyond set the stage for the interrogation of nearly every step in the reproductive cycle of vaccinia virus (VACV), a large DNA virus with about 200 genes. The reader may view this article as a work in progress, because I remain actively engaged in research at the National Institutes of Health (NIH) notwithstanding 50 memorable years there. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Three essays on utility regulation

NASA Astrophysics Data System (ADS)

Hlasny, Vladimir

To induce utilities in the gas distribution market to operate efficiently, US states have deployed consumer choice programs, price caps, and variations of sliding scale plans. My first essay studies the impact of these restructuring and deregulation efforts on consumer rates, using panel data from a custom survey of state commissions and the Department of Energy. I estimate the residential, small commercial and industrial price equations jointly, and use instrumental variables to control for the potentially endogenous demand and status of deregulation. Consumer choice programs lower the prices by 2.2-20.1% compared to the rate of return regulation, benefiting industrial consumers the most and households the least. These effects appear even one to two years prior to the programs' implementation, and become stronger over time. Price caps lower all prices by 0.0-20.0%, with the same ranking. The impacts of sliding scale plans are close to zero, between -2.6% and +4.0% The second paper evaluates health damages caused by air concentrations of SO2 under three alternative environmental policies leading to identical aggregate emissions: emission caps, a nationwide emission tax, and a system of tradable emission allowances such as the one currently used in the US. The numerical model of the industry finds generators' output, participation in energy trade and SO2 abatement effort under each policy. The resulting SO2 concentrations are used to derive the aggregate health damages using estimates in the medical literature. SO2 concentrations vary across policies even when the aggregate emissions are the same. These variations translate into substantially different losses for any individual state, and, nationwide, to hundreds of millions of dollars of difference in aggregate damages. Emission caps are found to lead to the lowest damages, outperforming the currently used system of allowances by 452 million. A uniform emission tax leads to very similar damages as the system of tradable allowances, in agreement with the theory. These results are consistent with prior academic studies, that emission allowances and uniform taxes may lead to higher damages than regulatory instruments that control regional emissions more closely. In terms of SO2 concentrations and health impacts, emission caps are shown to favor the southern and southeastern states, where they deliver 840 million lower damages than the system of allowances or an emission tax, while they deliver 390 million higher damages in the northern and northeastern states. In the third essay I compute health damages from SO2 under different assumptions on the relationship between the concentration levels and their marginal health impacts. I evaluate SO2 concentration profiles resulting under the three policies in the previous chapter. Using the ranges of marginal damage estimates in medical literature, emission caps are shown to lead to the lowest damages under all considered slopes, although their benefit over the system of tradable allowances falls as the slope of the marginal damage function increases. With the maxiμm slope consistent with current medical data, the savings in damages under the emission caps in the southern states fall to 670 million compared the system of allowances, while the excess in damages they cause in the north and the northeast rises to $600 million.

Purification and characterization of a hexanol-degrading enzyme extracted from apple

USDA-ARS?s Scientific Manuscript database

An enzyme having activity towards n-hexanol was purified from apple and its biochemical characteristics were analyzed. The purification steps consisted of sedimentation with ammonium sulfate, DEAE Sepharose Fast Flow ion exchange chromatography and Sephadex G-100 column. The obtained enzyme had a yi...

Structural features of the exocellular polysaccharides of Mycobacterium tuberculosis.

PubMed Central

Lemassu, A; Daffé, M

1994-01-01

The cell envelope which surrounds pathogenic mycobacteria is postulated to be a defence barrier against phagocytic cells and its outermost constituents have a tendency to accumulate in the culture medium. The present work demonstrates that the exocellular material of Mycobacterium tuberculosis contains large amounts of polysaccharides with only traces, if any at all, of lipids. Three types of polysaccharides were purified by anion-exchange and gel-filtration chromatography; all were found to be neutral compounds devoid of acyl substituents. They consisted of D-glucan, D-arabino-D-mannan and D-mannan, which were eluted from gel-filtration columns in positions corresponding to molecular masses of 123, 13 and 4 kDa respectively. Their predominant structural features were determined by the characterization of the per-O-methyl derivatives of enzymic, acetolysis and Smith-degradation products and by 1H- and 13C-n.m.r. spectroscopy of the purified polysaccharides, using mono- and two-dimensional homonuclear chemical-shift correlated spectroscopy and two-dimensional heteronuclear (1H/13C) spectroscopy. The glucan which represented up to 90% of the polysaccharides was composed of repeating units of five or six-->4-alpha-D-Glcp-1--> residues and a -->4-alpha-D-Glcp substituted at position 6 with an alpha-D-Glcp, indicating a glycogen-like highly branched structure not related to the so-called polysaccharide-II previously identified in tuberculin. The arabinomannan consisted of a mannan segment composed of a -->6-alpha-D-Man-1--> core substituted at some positions 2 with an alpha-D-Manp. The arabinan termini of the arabinomannan were found to be extensively capped with mannosyl residues. The possibility that these polysaccharides contribute to the persistence of the tubercle bacillus in the macrophage by molecular mimicry is discussed. PMID:8297342

Structural features of the exocellular polysaccharides of Mycobacterium tuberculosis.

PubMed

Lemassu, A; Daffé, M

1994-01-15

The cell envelope which surrounds pathogenic mycobacteria is postulated to be a defence barrier against phagocytic cells and its outermost constituents have a tendency to accumulate in the culture medium. The present work demonstrates that the exocellular material of Mycobacterium tuberculosis contains large amounts of polysaccharides with only traces, if any at all, of lipids. Three types of polysaccharides were purified by anion-exchange and gel-filtration chromatography; all were found to be neutral compounds devoid of acyl substituents. They consisted of D-glucan, D-arabino-D-mannan and D-mannan, which were eluted from gel-filtration columns in positions corresponding to molecular masses of 123, 13 and 4 kDa respectively. Their predominant structural features were determined by the characterization of the per-O-methyl derivatives of enzymic, acetolysis and Smith-degradation products and by 1H- and 13C-n.m.r. spectroscopy of the purified polysaccharides, using mono- and two-dimensional homonuclear chemical-shift correlated spectroscopy and two-dimensional heteronuclear (1H/13C) spectroscopy. The glucan which represented up to 90% of the polysaccharides was composed of repeating units of five or six-->4-alpha-D-Glcp-1--> residues and a -->4-alpha-D-Glcp substituted at position 6 with an alpha-D-Glcp, indicating a glycogen-like highly branched structure not related to the so-called polysaccharide-II previously identified in tuberculin. The arabinomannan consisted of a mannan segment composed of a -->6-alpha-D-Man-1--> core substituted at some positions 2 with an alpha-D-Manp. The arabinan termini of the arabinomannan were found to be extensively capped with mannosyl residues. The possibility that these polysaccharides contribute to the persistence of the tubercle bacillus in the macrophage by molecular mimicry is discussed.

Efficacy and safety of moxifloxacin in community acquired pneumonia: a prospective, multicenter, observational study (CAPRIVI).

PubMed

Kuzman, Ilija; Bezlepko, Alexandr; Kondova Topuzovska, Irena; Rókusz, László; Iudina, Liudmyla; Marschall, Hans-Peter; Petri, Thomas

2014-06-30

Community acquired pneumonia (CAP) is a major cause of morbidity, hospitalization, and mortality worldwide. Management of CAP for many patients requires rapid initiation of empirical antibiotic treatment, based on the spectrum of activity of available antimicrobial agents and evidence on local antibiotic resistance. Few data exist on the severity profile and treatment of hospitalized CAP patients in Eastern and Central Europe and the Middle East, in particular on use of moxifloxacin (Avelox®), which is approved in these regions. CAPRIVI (Community Acquired Pneumonia: tReatment wIth AVelox® in hospItalized patients) was a prospective observational study in 12 countries: Croatia, France, Hungary, Kazakhstan, Jordan, Kyrgyzstan, Lebanon, Republic of Moldova, Romania, Russia, Ukraine, and Macedonia. Patients aged >18 years were treated with moxifloxacin 400 mg daily following hospitalization with a CAP diagnosis. In addition to efficacy and safety outcomes, data were collected on patient history and disease severity measured by CRB-65 score. 2733 patients were enrolled. A low severity index (i.e., CRB-65 score <2) was reported in 87.5% of CAP patients assessed (n=1847), an unexpectedly high proportion for hospitalized patients. Moxifloxacin administered for a mean of 10.0 days (range: 2.0 to 39.0 days) was highly effective: 96.7% of patients in the efficacy population (n=2152) improved and 93.2% were cured of infection during the study. Severity of infection changed from "moderate" or "severe" in 91.8% of patients at baseline to "no infection" or "mild" in 95.5% at last visit. In the safety population (n=2595), 127 (4.9%) patients had treatment-emergent adverse events (TEAEs) and 40 (1.54%) patients had serious TEAEs; none of these 40 patients died. The safety results were consistent with the known profile of moxifloxacin. The efficacy and safety profiles of moxifloxacin at the recommended dose of 400 mg daily are characterized in this large observational study of hospitalized CAP patients from Eastern and Central Europe and the Middle East. The high response rate in this study, which included patients with a range of disease severities, suggests that treatment with broader-spectrum drugs such as moxifloxacin is appropriate for patients with CAP who are managed in hospital. ClinicalTrials.gov identifier: NCT00987792.

Volatile-rich Crater Interior Deposits in the Polar Regions of Mars: Evidence for Ice Cap Advance and Retreat

NASA Technical Reports Server (NTRS)

Russell, Patrick S.; Head, James W.; Hecht, Michael H.

2003-01-01

Many craters on Mars are partially filled by distinctive material emplaced by post-impact processes. This crater fill material is an interior mound which is generally separated from the walls of the crater by a trough that may be continuous along the crater circumference (i.e. a ring-shaped trough), or which may only partially contact the crater walls (i.e. a crescent-shaped trough). The fill deposit is frequently offset from the crater center and may be asymmetric in plan view. Populations of such craters include those in the circum-south polar cap region, in Arabia Terra, associated with the Medusae Fossae Formation, and in the northern lowlands proximal to the north polar cap. We focus on those craters in circumpolar regions and assess their relationship to polar cap advance and retreat, especially the possibility that fill material represents remnants of a formerly larger contiguous cap. Volatile-rich deposits have the property of being modifiable by the local stability of the solid volatile, which is governed by local energy balance. Here we test the hypothesis that asymmetries in volatile fill shape, profile, and center-location within a crater result from asymmetries in local energy balance within the crater, due mainly to variation of solar insolation and radiative effects of the crater walls over the crater interior. Model profiles of crater fill are compared with MOLA topographic profiles to assess this hypothesis. If asymmetry in morphology and location of crater fill are consistent with radiative-dominated asymmetries in energy budget within the crater, then 1) the volatile-rich composition of the fill is supported (this process should not be effective at shaping volcanic or sedimentary deposits), and 2) the dominant factor determining the observed shape of volatile-rich crater fill is the local radiative energy budget (and erosive processes such as eolian deflation are secondary or unnecessary). We also use a geographic and energy model approach to specifically test the idea that material in partially filled craters around the south pole may once have been contiguous to the cap and may have been sustained and modified by radiative processes specific to the crater environment (as opposed to the surrounding plains) as the cap retreated.

Effect of high-latitude ionospheric convection on Sun-aligned polar caps

NASA Technical Reports Server (NTRS)

Sojka, J. J.; Zhu, L.; Crain, D. J.; Schunk, R. W.

1994-01-01

A coupled magnetospheric-ionospheric (M-I) magnetohydrodynamic (MHD) model has been used to simulate the formation of Sun-aligned polar cap arcs for a variety of interplanetary magnetic field (IMF) dependent polar cap convection fields. The formation process involves launching an Alfven shear wave from the magnetosphere to the ionosphere where the ionospheric conductance can react self-consistently to changes in the upward currents. We assume that the initial Alfven shear wave is the result of solar wind-magnetosphere interactions. The simulations show how the E region density is affected by the changes in the electron precipitation that are associated with the upward currents. These changes in conductance lead to both a modified Alfven wave reflection at the ionosphere and the generation of secondary Alfven waves in the ionosphere. The ensuing bouncing of the Alfven waves between the ionosphere and magnetosphere is followed until an asymptotic solution is obtained. At the magnetosphere the Alfven waves reflect at a fixed boundary. The coupled M-I Sun-aligned polar cap arc model of Zhu et al.(1993a) is used to carry out the simulations. This study focuses on the dependence of the polar cap arc formation on the background (global) convection pattern. Since the polar cap arcs occur for northward and strong B(sub y) IMF conditions, a variety of background convection patterns can exist when the arcs are present. The study shows that polar cap arcs can be formed for all these convection patterns; however, the arc features are dramatically different for the different patterns. For weak sunward convection a relatively confined single pair of current sheets is associated with the imposed Alfven shear wave structure. However, when the electric field exceeds a threshold, the arc structure intensifies, and the conductance increases as does the local Joule heating rate. These increases are faster than a linear dependence on the background electric field strength. Furthermore, above the threshold, the single current sheet pair splits into multiple current sheet pairs. For the fixed initial ionospheric and magnetospheric conditions used in this study, the separation distance between the current pairs was found to be almost independent of the background electric field strength. For either three-cell or distorted two-cell background convection patterns the arc formation favored the positive B(sub y) case in the northern hemisphere.

Photo-Redox Activated Drug Delivery Systems Operating Under Two Photon Excitation in the Near-IR

PubMed Central

Guardado-Alvarez, Tania M.; Devi, Lekshmi Sudha; Vabre, Jean-Marie; Pecorelli, Travis; Schwartz, Benjamin J.; Durand, Jean-Olivier; Mongin, Olivier; Blanchard-Desce, Mireille; Zink, Jeffrey I.

2014-01-01

We report the design and synthesis of a nano-container consisting of mesoporous silica nanoparticles with the pore openings covered by “snap-top” caps that are opened by near-IR light. A photo transducer molecule that is a reducing agent in an excited electronic state is covalently attached to the system. Near IR two-photon excitation causes inter-molecular electron transfer that reduces a disulfide bond holding the cap in place, thus allowing the cargo molecules to escape. We describe the operation of the “snap-top” release mechanism by both one- and two-photon activation. This system presents a proof of concept of a near-IR photoredox-induced nanoparticle delivery system that may lead to a new type of photodynamic drug release therapy. PMID:24647752

Photo-redox activated drug delivery systems operating under two photon excitation in the near-IR.

PubMed

Guardado-Alvarez, Tania M; Devi, Lekshmi Sudha; Vabre, Jean-Marie; Pecorelli, Travis A; Schwartz, Benjamin J; Durand, Jean-Olivier; Mongin, Olivier; Blanchard-Desce, Mireille; Zink, Jeffrey I

2014-05-07

We report the design and synthesis of a nano-container consisting of mesoporous silica nanoparticles with the pore openings covered by "snap-top" caps that are opened by near-IR light. A photo transducer molecule that is a reducing agent in an excited electronic state is covalently attached to the system. Near IR two-photon excitation causes inter-molecular electron transfer that reduces a disulfide bond holding the cap in place, thus allowing the cargo molecules to escape. We describe the operation of the "snap-top" release mechanism by both one- and two-photon activation. This system presents a proof of concept of a near-IR photoredox-induced nanoparticle delivery system that may lead to a new type of photodynamic drug release therapy.

A study of the electric field in an open magnetospheric model

NASA Technical Reports Server (NTRS)

Stern, D. P.

1973-01-01

Recently, Svalgaard and Heppner reported two separate features of the polar electromagnetic field that correlate with the dawn-dusk component of the interplanetary magnetic field. This work attempts to explain these findings in terms of properties of the open magnetosphere. The topology and qualitative properties of the open magnetosphere are first studied by means of a simple model, consisting of a dipole in a constant field. Many such properties are found to depend on the separation line, a curve connecting neutral points and separating different field line regimes. In the simple model it turns out that the electric field in the central polar cap tends to point from dawn to dusk for a wide variety of external fields, but, near the boundary of the polar cap, electric equipotentials are deformed into crescents.

Design of an optimised readout architecture for phase-change probe memory using Ge2Sb2Te5 media

NASA Astrophysics Data System (ADS)

Wang, Lei; Wright, C. David; Aziz, Mustafa M.; Yang, Ci-Hui; Yang, Guo-Wei

2014-02-01

Phase-change probe memory has recently received considerable attention on its writing performance, while its readout performance is rarely evaluated. Therefore, a three-dimensional readout model has been developed for the first time to calculate the reading contrast by varying the electrical conductivities and the thickness of the capping and under layers as well as the thickness of the Ge2Sb2Te5 layer. It is found that a phase-change probe architecture, consisting of a 10 nm Ge2Sb2Te5 layer sandwiched by a 2 nm, 50 Ω-1 m-1 capping layer and a 40 nm, 5 × 106 Ω-1 m-1 under layer, has the capability of providing the optimal readout performance.

Block Copolymer Adhesion Measured by Contact Mechanics Methods

NASA Astrophysics Data System (ADS)

Falsafi, A.; Bates, S.; Tirrell, M.; Pocius, A. V.

1997-03-01

Adhesion measurements for a series of polyolefin diblocks and triblocks are presented. These materials have poly(ethylene-propylene) or poly(ethyl-ethylene) rubbery block, and semicrystalline polyethylene block as physical crosslinker. The experiments consist of compression and decompression profiles of contact area between the samples as a function of normal load, analyzed by the JKR Theory. The samples are prepared either by formation of caps from the bulk material in melting and subsequent cooling, and/or coating them in thin films on surface modified elastic foundations of polydimethylsiloxane caps. The latter minimizes the viscoelastic losses which are dominant in the bulk of material. The effect of molecular architecture and microstructure on adhesion energy and dynamics of separation, obtained from decompression experiments, is discussed in view of their influence on molecular arrangements at the contacting surfaces.

Regulators of Androgen Action Resource: a one-stop shop for the comprehensive study of androgen receptor action.

PubMed

DePriest, Adam D; Fiandalo, Michael V; Schlanger, Simon; Heemers, Frederike; Mohler, James L; Liu, Song; Heemers, Hannelore V

2016-01-01

Androgen receptor (AR) is a ligand-activated transcription factor that is the main target for treatment of non-organ-confined prostate cancer (CaP). Failure of life-prolonging AR-targeting androgen deprivation therapy is due to flexibility in steroidogenic pathways that control intracrine androgen levels and variability in the AR transcriptional output. Androgen biosynthesis enzymes, androgen transporters and AR-associated coregulators are attractive novel CaP treatment targets. These proteins, however, are characterized by multiple transcript variants and isoforms, are subject to genomic alterations, and are differentially expressed among CaPs. Determining their therapeutic potential requires evaluation of extensive, diverse datasets that are dispersed over multiple databases, websites and literature reports. Mining and integrating these datasets are cumbersome, time-consuming tasks and provide only snapshots of relevant information. To overcome this impediment to effective, efficient study of AR and potential drug targets, we developed the Regulators of Androgen Action Resource (RAAR), a non-redundant, curated and user-friendly searchable web interface. RAAR centralizes information on gene function, clinical relevance, and resources for 55 genes that encode proteins involved in biosynthesis, metabolism and transport of androgens and for 274 AR-associated coregulator genes. Data in RAAR are organized in two levels: (i) Information pertaining to production of androgens is contained in a 'pre-receptor level' database, and coregulator gene information is provided in a 'post-receptor level' database, and (ii) an 'other resources' database contains links to additional databases that are complementary to and useful to pursue further the information provided in RAAR. For each of its 329 entries, RAAR provides access to more than 20 well-curated publicly available databases, and thus, access to thousands of data points. Hyperlinks provide direct access to gene-specific entries in the respective database(s). RAAR is a novel, freely available resource that provides fast, reliable and easy access to integrated information that is needed to develop alternative CaP therapies. Database URL: http://www.lerner.ccf.org/cancerbio/heemers/RAAR/search/. © The Author(s) 2016. Published by Oxford University Press.

High-pressure jet cutters improve capping operations

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

Abel, L.W.; Campbell, P.J.; Bowden, J.R. Sr.

1995-05-08

Advances in abrasive cutting technology have improved the methods for removing damaged equipment and preparing wellheads for capping. This technology, much of which was refined during well control operations in Kuwait in 1991, can improve the safety and efficiency of capping jobs by cutting wellheads or casing quickly and cleanly. The majority of well control jobs involve one of three types of capping operations: capping to a flange, capping by installing a wellhead, or capping to a casing stub. Capping operations are often the first major step in regaining control of the well during blowout intervention. Proper planning of amore » capping operation must take into account the mass flow rate, combustible nature of the flow, well bore geometry, and operations in the post-capping phase of the project. The paper discusses capping vehicles, tree removal, jet cutters, capping to a flange, capping to a stub, swallowing the stub, spin-on technique, capping on fire, stinging, offshore blowouts, firefighting, pollution control, intervention equipment, and rig removal.« less

Observations of the northern seasonal polar cap on Mars: I. Spring sublimation activity and processes

USGS Publications Warehouse

Hansen, C.J.; Byrne, S.; Portyankina, G.; Bourke, M.; Dundas, C.; McEwen, A.; Mellon, M.; Pommerol, A.; Thomas, N.

2013-01-01

Spring sublimation of the seasonal CO2 northern polar cap is a dynamic process in the current Mars climate. Phenomena include dark fans of dune material propelled out onto the seasonal ice layer, polygonal cracks in the seasonal ice, sand flow down slipfaces, and outbreaks of gas and sand around the dune margins. These phenomena are concentrated on the north polar erg that encircles the northern residual polar cap. The Mars Reconnaissance Orbiter has been in orbit for three Mars years, allowing us to observe three northern spring seasons. Activity is consistent with and well described by the Kieffer model of basal sublimation of the seasonal layer of ice applied originally in the southern hemisphere. Three typical weak spots have been identified on the dunes for escape of gas sublimed from the bottom of the seasonal ice layer: the crest of the dune, the interface of the dune with the interdune substrate, and through polygonal cracks in the ice. Pressurized gas flows through these vents and carries out material entrained from the dune. Furrows in the dunes channel gas to outbreak points and may be the northern equivalent of southern radially-organized channels (“araneiform” terrain), albeit not permanent. Properties of the seasonal CO2 ice layer are derived from timing of seasonal events such as when final sublimation occurs. Modification of dune morphology shows that landscape evolution is occurring on Mars today, driven by seasonal activity associated with sublimation of the seasonal CO2 polar cap.

Investigation of advanced pre- and post-equalization schemes in high-order CAP modulation based high-speed indoor VLC transmission system

NASA Astrophysics Data System (ADS)

Wang, Yiguang; Chi, Nan

2016-10-01

Light emitting diodes (LEDs) based visible light communication (VLC) has been considered as a promising technology for indoor high-speed wireless access, due to its unique advantages, such as low cost, license free and high security. To achieve high-speed VLC transmission, carrierless amplitude and phase (CAP) modulation has been utilized for its lower complexity and high spectral efficiency. Moreover, to compensate the linear and nonlinear distortions such as frequency attenuation, sampling time offset, LED nonlinearity etc., series of pre- and post-equalization schemes should be employed in high-speed VLC systems. In this paper, we make an investigation on several advanced pre- and postequalization schemes for high-order CAP modulation based VLC systems. We propose to use a weighted preequalization technique to compensate the LED frequency attenuation. In post-equalization, a hybrid post equalizer is proposed, which consists of a linear equalizer, a Volterra series based nonlinear equalizer, and a decision-directed least mean square (DD-LMS) equalizer. Modified cascaded multi-modulus algorithm (M-CMMA) is employed to update the weights of the linear and the nonlinear equalizer, while DD-LMS can further improve the performance after the preconvergence. Based on high-order CAP modulation and these equalization schemes, we have experimentally demonstrated a 1.35-Gb/s, a 4.5-Gb/s and a 8-Gb/s high-speed indoor VLC transmission systems. The results show the benefit and feasibility of the proposed equalization schemes for high-speed VLC systems.