Sample records for lambda gt11 expression

  1. Discovery of a protein phosphatase activity encoded in the genome of bacteriophage lambda. Probable identity with open reading frame 221.

    PubMed

    Cohen, P T; Cohen, P

    1989-06-15

    Infection of Escherichia coli with phage lambda gt10 resulted in the appearance of a protein phosphatase with activity towards 32P-labelled casein. Activity reached a maximum near the point of cell lysis and declined thereafter. The phosphatase was stimulated 30-fold by Mn2+, while Mg2+ and Ca2+ were much less effective. Activity was unaffected by inhibitors 1 and 2, okadaic acid, calmodulin and trifluoperazine, distinguishing it from the major serine/threonine-specific protein phosphatases of eukaryotic cells. The lambda phosphatase was also capable of dephosphorylating other substrates in the presence of Mn2+, although activity towards 32P-labelled phosphorylase was 10-fold lower, and activity towards phosphorylase kinase and glycogen synthase 25 50-fold lower than with casein. No casein phosphatase activity was present in either uninfected cells, or in E. coli infected with phage lambda gt11. Since lambda gt11 lacks part of the open reading frame (orf) 221, previously shown to encode a protein with sequence similarity to protein phosphatase-1 and protein phosphatase-2A of mammalian cells [Cohen, Collins, Coulson, Berndt & da Cruz e Silva (1988) Gene 69, 131-134], the results indicate that ORF221 is the protein phosphatase detected in cells infected with lambda gt10. Comparison of the sequence of ORF221 with other mammalian protein phosphatases defines three highly conserved regions which are likely to be essential for function. The first of these is deleted in lambda gt11.

  2. Safety and Efficacy of Pegylated Interferon Lambda, Ribavirin, and Daclatasvir in HCV and HIV-Coinfected Patients.

    PubMed

    Nelson, Mark; Rubio, Rafael; Lazzarin, Adriano; Romanova, Svetlana; Luetkemeyer, Annie; Conway, Brian; Molina, Jean-Michel; Xu, Dong; Srinivasan, Subasree; Portsmouth, Simon

    2017-03-01

    To evaluate the efficacy and safety of pegylated interferon-lambda-1a (Lambda)/ribavirin (RBV)/daclatasvir (DCV) for treatment of patients coinfected with chronic hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Treatment-naive patients were assigned to cohort A [HCV genotype (GT)-2 or -3] or cohort B [HCV GT-1(a or b) or -4]. All patients received Lambda/RBV/DCV for the first 12 weeks; cohort A received Lambda/RBV for an additional 12 weeks, followed by 24 weeks of follow-up, and cohort B received response-guided therapy. The primary endpoint was the proportion of patients who achieved a sustained virologic response at post-treatment week 12 (SVR12). In cohort A (n = 104), 84.6% achieved SVR12 (95.0% in GT-2; 83.1% in GT-3). In cohort B (n = 196), 76.0% achieved SVR12 (71.7% in GT-1a; 86.0% in GT-1b; 70.7% in GT-4). Rates of discontinuation due to adverse events (AEs) (3.8% and 6.1%) and serious AEs (5.8% and 6.1%) were low in cohorts A and B, respectively. In addition, treatment with Lambda/RBV/DCV had little impact on CD4 counts. SVR12 rates with Lambda/RBV/DCV in an HCV/HIV-coinfected population ranged from 71.7% to 95.0%. Treatment was generally well tolerated, with a low proportion of patients discontinuing due to AEs. Clinical trial registration NCT01866930.

  3. Characterization of a 29.4-kilodalton structural protein of Giardia lamblia and localization to the ventral disk [corrected

    PubMed Central

    Aggarwal, A; Adam, R D; Nash, T E

    1989-01-01

    The amino acid sequence of a 29.4-kilodalton [corrected] structural protein located in the ventral disk and axostyle of Giardia lamblia was determined. Clone lambda M16 from a mung bean expression library in lambda gt11 expressed a fusion protein recognized by three different isolate-specific antisera and sera from G. lamblia-infected gerbils. One of the three EcoRI fragments (M16; 1.26 kilobases) encoded the recognized protein. Sequence analysis revealed a single open reading frame of 813 base pairs. Two areas showed conservation of the positions of some amino acids. The abundance of arginine, glutamic acid, and threonine was increased. Two potential alpha-helical regions were deduced in the regions of repeats. Antisera to the M16 fusion protein reacted specifically with internal components of the ventral disk and axostyle, as well as Giardia fractions enriched for ventral disk structural proteins. An identical protein was recognized in different isolates by anti-M16, and a single identical band was recognized in Southern blots using the M16 1.26-kilobase fragment as a probe. Therefore, the 29.4-kilodaltion [corrected] protein appears to be highly conserved compared with variant surface proteins. Images PMID:2925253

  4. Molecular cloning of a small prostate protein, known as beta-microsemenoprotein, PSP94 or beta-inhibin, and demonstration of transcripts in non-genital tissues.

    PubMed

    Ulvsbäck, M; Lindström, C; Weiber, H; Abrahamsson, P A; Lilja, H; Lundwall, A

    1989-11-15

    In order to study the gene expression of the seminal plasma protein beta-microseminoprotein, also known as PSP94 and beta-inhibin, clones encoding this protein were isolated from a cDNA library constructed in lambda gt11. Nucleotide sequencing confirmed the structure of a previously cloned cDNA. By northern blot analysis identical sized transcripts were demonstrated in the prostate, the respiratory (tracheal, bronchial and lung) tissues and the antrum part of the gastric mucosa. Thus, the protein is not primarily associated with male reproductive function. Although probably of no physiological significance, a slight structural similarity to the ovarian inhibin beta-chains was identified in the C-terminal half of the molecule.

  5. Purification, cDNA cloning, and regulation of lysophospholipase from rat liver.

    PubMed

    Sugimoto, H; Hayashi, H; Yamashita, S

    1996-03-29

    A lysophospholipase was purified 506-fold from rat liver supernatant. The preparation gave a single 24-kDa protein band on SDS-polyacrylamide gel electrophoresis. The enzyme hydrolyzed lysophosphatidylcholine, lysophosphatidylethanolamine, lysophosphatidylinositol, lysophosphatidylserine, and 1-oleoyl-2-acetyl-sn-glycero-3-phosphocholine at pH 6-8. The purified enzyme was used for the preparation of antibody and peptide sequencing. A cDNA clone was isolated by screening a rat liver lambda gt11 cDNA library with the antibody, followed by the selection of further extended clones from a lambda gt10 library. The isolated cDNA was 2,362 base pairs in length and contained an open reading frame encoding 230 amino acids with a Mr of 24,708. The peptide sequences determined were found in the reading frame. When the cDNA was expressed in Escherichia coli cells as the beta-galactosidase fusion, lysophosphatidylcholine-hydrolyzing activity was markedly increased. The deduced amino acid sequence showed significant similarity to Pseudomonas fluorescence esterase A and Spirulina platensis esterase. The three sequences contained the GXSXG consensus at similar positions. The transcript was found in various tissues with the following order of abundance: spleen, heart, kidney, brain, lung, stomach, and testis = liver. In contrast, the enzyme protein was abundant in the following order: testis, liver, kidney, heart, stomach, lung, brain, and spleen. Thus the mRNA abundance disagreed with the level of the enzyme protein in liver, testis, and spleen. When HL-60 cells were induced to differentiate into granulocytes with dimethyl sulfoxide, the 24-kDa lysophospholipase protein increased significantly, but the mRNA abundance remained essentially unchanged. Thus a posttranscriptional control mechanism is present for the regulation of 24-kDa lysophospholipase.

  6. Characterization of embryo-specific genes

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

    Sung, Z.R.

    1988-01-01

    The objective of the proposed research is to characterize the structure and function of a set of genes whose expression is regulated in embryo development, and that are not expressed in mature tissues -- the embryogenic genes. In order to isolate these genes, we immunized a rabbit with total extracts of somatic embryos of carrot, and enriched the anti-embryo antiserum for antibodies reacting with extracts of carrot somatic embryos. Using this enriched antiserum, we screened a lambda gt11 cDNA library constructed from embryo poly A{sup +} RNA, and isolated 10 cDNA clones that detect embryogenic mRNAs. Monospecific antibodies have beenmore » purified for proteins corresponding to each cDNA sequence. Four cDNA clones were further characterized in terms of the expression of their corresponding mRNA and protein in somatic embryos of carrot. In some cases, comparable gene sequences or products have been detected in somatic and zygotic embryos of other plant species. The characteristics of these 4 cDNA clones -- clone Nos. 8, 59, and 66 -- are described in this report. 3 figs.« less

  7. Molecular and Physiological Analysis of a Heat-Shock Response in Wheat 1

    PubMed Central

    McElwain, Elizabeth F.; Spiker, Steven

    1992-01-01

    We have isolated two cDNA clones from wheat (Triticum aestivum L. var Stephens), designated WHSP16.8 and WHSP16.9, that are highly similar in sequence to the low molecular weight heat-shock protein genes previously isolated from soybean. RNA blot analysis confirms that these sequences are present in heat-shocked wheat seedlings, but not in control tissues. The WHSP16.8 and WHSP16.9 cDNAs were isolated by screening a lambda gt11 expression library with antibodies to HMGc (a chromosomal protein of wheat). Immunoblot analysis has demonstrated that the antibodies raised against HMGc also recognize a group of proteins that are induced by heat shock and have molecular weights (estimated by sodium dodecyl sulfate electrophoresis) consistent with the molecular weights of the proteins deduced from the sequences of the cDNAs. ImagesFigure 3Figure 4Figure 5 PMID:16669058

  8. Expression profiles of gonadotropins and their receptors during 17α-methyltestosterone implantation-induced sex change in the orange-spotted grouper (Epinephelus coioides).

    PubMed

    Hu, Xuesong; Liu, Xiaochun; Zhang, Haifa; Zhang, Yong; Li, Shuisheng; Sang, Qing; Wang, Qian; Luo, Wenna; Liu, Qizhi; Lu, Danqi; Meng, Zining; Lin, Haoran

    2011-06-01

    It is known that the hypothalamic-pituitary-gonadal axis participates in the sex change of hermaphrodite teleosts, and gonadal steroid hormones mediate this physiological process. The secretion of gonadal steroids is directly regulated by signaling pathways involving gonadotropins (GtHs) and gonadotropin receptors (GtHRs) in teleosts. To gain insight into the involvement of GtH/GtHR systems in the sex change process, cDNAs encoding follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) were firstly isolated from gonads of orange-spotted grouper (Epinephelus coioides), a protogynous hermaphrodite fish. Reverse transcription-PCR (RT-PCR) analysis demonstrated that the expression of the FSHR was confined to the brain, pituitary gland, ovary, and testis, while the LHR was expressed only in the brain, ovary, and testis. Furthermore, the expression profiles of GtH subunits (FSHβ and LHβ) and their receptors were analyzed in parallel with the serum levels of estradiol-17β (E(2) ), testosterone (T), and 11-ketotestosterone (11-KT) during 17α-methyltestosterone (MT)-induced sex change. Quantitative real-time PCR determined that the abundances of FSHβ and FSHR were significantly inhibited after MT treatment for 2 and 4 weeks, but subsequently returned to the control level after 6 weeks. In contrast, the mRNA levels of LHβ and LHR were significantly elevated throughout the sex change process. During MT-induced sex change, serum concentrations of E(2) remained constant while T and 11-KT levels were significantly increased. Taken together, our results suggest that GtH/GtHR systems are involved in MT-induced sex change, and two signaling pathways may have distinct roles in modulating the variations of the corresponding steroid hormones in the orange-spotted grouper. Copyright © 2011 Wiley-Liss, Inc.

  9. O-acetylserine(thiol)lyase from spinach (Spinacia oleracea L.) leaf: cDNA cloning, characterization, and overexpression in Escherichia coli of the chloroplast isoform.

    PubMed

    Rolland, N; Droux, M; Lebrun, M; Douce, R

    1993-01-01

    The last enzymatic step for L-cysteine biosynthesis is catalyzed by O-acetylserine(thiol)lyase (OASTL, EC 4.2.99.8) which synthesizes L-cysteine from O-acetylserine and "sulfide." We have isolated and characterized a full-length cDNA (1432 bp) from a lambda gt11 library of spinach leaf encoding the complete precursor of the chloroplast isoform. The 1149-nucleotide open reading frame coding for O-acetylserine(thiol)lyase was in the direction opposite that of the lambda gt11 beta-galactosidase gene. The derived amino acid sequence indicates that the protein precursor consists of 383 amino acid residues including a N-terminal presequence peptide of 52 residues. The amino acid sequence of mature spinach chloroplast O-acetylserine(thiol)lyase shows 40 and 57% homology with its bacterial counterparts. Sequence comparison with several pyridoxal 5'-phosphate-containing proteins reveals the presence of a lysine residue assumed to be involved in cofactor binding. A synthetic cDNA was constructed, coding for the entire 331-amino-acid mature O-acetylserine(thiol)lyase and for an initiating methionine. A high level of expression of the active mature chloroplast isoform was achieved in an Escherichia coli strain carrying the T7 RNA polymerase system (F. W. Studier, A. H. Rosenberg, J. J. Dunn, and J. W. Dubendorff, 1990, in Methods in Enzymology, D. V. Goeddel, Ed., Vol. 185, pp. 60-89, Academic Press, San Diego, CA). Addition of pyridoxine to the bacterial growth medium enhanced the enzyme activity due to the recombinant protein. The extent of production is 25-fold higher than in chloroplast from spinach leaves and the recombinant protein presents the relative molecular mass and immunological properties of the natural enzyme from spinach leaf chloroplast. This work, together with our previous biochemical studies, are in accordance with a prokaryotic type enzyme for L-cysteine biosynthesis in higher plant chloroplasts. Southern blot analysis indicated that O-acetylserine(thiol)lyase is encoded by multiple genes in the spinach leaf genomic DNA.

  10. A Randomized Study of Peginterferon Lambda-1a Compared to Peginterferon Alfa-2a in Combination with Ribavirin and Telaprevir in Patients with Genotype-1 Chronic Hepatitis C.

    PubMed

    Flisiak, Robert; Shiffman, Mitchell; Arenas, Juan; Cheinquer, Hugo; Nikitin, Igor; Dong, Yuping; Rana, Khurram; Srinivasan, Subasree

    2016-01-01

    A randomized, double-blind, multinational, phase 3 study was conducted comparing the efficacy and safety of peginterferon lambda-1a (Lambda)/ribavirin (RBV)/telaprevir (TVR) vs. peginterferon alfa-2a (Alfa)/RBV/TVR in patients with chronic hepatitis C virus (HCV) genotype-1 (GT-1) infection. Patients (treatment-naïve or relapsers on prior Alfa/RBV treatment) were randomly assigned in a 2:1 ratio to receive Lambda/RBV/TVR or Alfa/RBV/TVR. Total duration of treatment was either 24 or 48 weeks (response-guided treatment), with TVR administered for the first 12 weeks. The primary endpoint was the proportion of patients who achieved a sustained virologic response at post treatment week 12 (SVR12), which was tested for noninferiority of Lambda/RBV/TVR. A total of 838 patients were enrolled, and 617 were treated; 411 and 206 patients received Lambda/RBV/TVR and Alfa/RBV/TVR, respectively. The majority of patients were treatment-naïve, with HCV GT-1b and a high baseline viral load (≥800,000 IU/mL). Less than 10% of patients had cirrhosis (Lambda, 7.5%; Alfa, 6.8%). Lambda/RBV/TVR did not meet the criterion for noninferiority (lower bound of the treatment difference interval was -12.3%); the SVR12 in all patients (modified intent-to-treat) was 76.2% in the Lambda arm and 82.0% in the Alfa arm. Overall, the frequency of adverse events in each arm was comparable (Lambda, 91.7%; Alfa, 97.1%). As expected based on the safety profile of the 2 interferons, there were more hepatobiliary events observed in the Lambda arm and more hematologic events in the Alfa arm. In this comparison of Lambda/RBV/TVR and Alfa/RBV/TVR in patients who were treatment-naïve or had relapsed on prior Alfa/RBV treatment, Lambda failed to demonstrate noninferiority based on SVR12 results. Treatment with Lambda/RBV/TVR was associated with a higher incidence of relapse. More patients discontinued Lambda/RBV/TVR treatment during the first 4 weeks of study treatment, mainly due to hepatobiliary-related events, and more Lambda patients were lost to follow-up.

  11. Concise expression of a classical radiation spectrum

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

    Wang, C.

    1993-06-01

    In this paper we present a concise expression of the classical electromagnetic radiation spectrum of a moving charge. It is shown to be equivalent to the often used and much more complicated form derived from the Lienard-Wiechert potentials when the observation distance [ital R] satisfies the condition [ital R][much gt][gamma][lambda]. The expression reveals a relationship between the radiation spectrum and the motion of the radiation source. It also forms the basis of an efficient computing approach, which is of practical value in numerical calculations of the spectral output of accelerated charges. The advantages of this approach for analytical and numericalmore » applications are discussed and the bending-magnet synchrotron radiation spectrum is calculated according to the approach.« less

  12. A pilot study of randomized clinical controlled trial of gait training in subacute stroke patients with partial body-weight support electromechanical gait trainer and functional electrical stimulation: six-month follow-up.

    PubMed

    Ng, Maple F W; Tong, Raymond K Y; Li, Leonard S W

    2008-01-01

    This study aimed to assess the effectiveness of gait training using an electromechanical gait trainer with or without functional electrical stimulation for people with subacute stroke. This was a nonblinded randomized controlled trial with a 6-month follow-up. Fifty-four subjects were recruited within 6 weeks after stroke onset and were randomly assigned to 1 of 3 gait intervention groups: conventional overground gait training treatment (CT, n=21), electromechanical gait trainer (GT, n=17) and, electromechanical gait trainer with functional electrical stimulation (GT-FES, n=16). All subjects were to undergo an assigned intervention program comprising a 20-minute session every weekday for 4 weeks. The outcome measures were Functional Independence Measure, Barthel Index, Motricity Index leg subscale, Elderly Mobility Scale (EMS), Berg Balance Scale, Functional Ambulatory Category (FAC), and 5-meter walking speed test. Assessments were made at baseline, at the end of the 4-week intervention program, and 6 months after the program ended. By intention-to-treat and multivariate analysis, statistically significant differences showed up in EMS (Wilks' lambda=0.743, P=0.005), FAC (Wilks' lambda=0.744, P=0.005) and gait speed (Wilks' lambda=0.658, P<0.0001). Post hoc analysis (univariate 2-way ANCOVA) revealed that the GT and GT-FES groups showed significantly better improvement in comparison with the CT group at the end of the 4 weeks of training and in the 6-month follow-up. For the early stage after stroke, this study indicated a higher effectiveness in poststroke gait training that used an electromechanical gait trainer compared with conventional overground gait training. The training effect was sustained through to the 6-month follow-up after the intervention.

  13. Daclatasvir/peginterferon lambda-1a/ribavirin in patients with chronic HCV infection and haemophilia who are treatment naïve or prior relapsers to peginterferon alfa-2a/ribavirin.

    PubMed

    Santagostino, E; Pol, S; Olveira, A; Reesink, H W; van Erpecum, K; Bogomolov, P; Xu, D; Critelli, L; Srinivasan, S; Cooney, E

    2016-09-01

    This study explores the potential role of a novel interferon-containing regimen for treatment of patients with chronic hepatitis C (CHC) and underlying haemophilia. This trial (NCT01741545) was an open-label, non-randomized phase 3 study, which included adult haemophiliacs with hepatitis C virus (HCV). Patients with HCV genotypes (GT)-2 or -3 were treated with Lambda-IFN/ribavirin (RBV)/daclatasvir (DCV) for 12 weeks (cohort A). Patients with HCV GT-1b or -4 were treated with Lambda-IFN/RBV/DCV for 12 weeks, followed by Lambda-IFN/RBV for an additional 12 weeks (cohort B). The primary endpoint was the proportion of patients with a sustained virologic response at post-treatment follow-up week 12 (SVR12). Clinical development of Lambda-IFN was discontinued during this trial leading to study termination before a 24-week post-treatment follow-up was obtained for all participants. Overall, 51 patients were treated (cohort A, n = 12; cohort B, n = 39). The proportion of patients achieving SVR12 was 92% in cohort A and 90% in cohort B. Therapy was generally well tolerated. The most common adverse events (AEs) were related to elevations in serum transaminases and/or bilirubin. Five serious AEs, four discontinuations due to AEs, and no deaths were reported. The rate of grade 3-4 bilirubin elevations was 17-18% across cohorts. Lambda-IFN/RBV/DCV treatment demonstrated a high SVR rate and was generally well tolerated with a safety profile consistent with expectations for this special patient population. This study supports use of DCV as part of a combination treatment regimen for haemophiliacs with CHC. © 2016 John Wiley & Sons Ltd.

  14. A DNA fragment of Leptospira interrogans encodes a protein which shares epitopes with equine cornea.

    PubMed

    Lucchesi, P M; Parma, A E

    1999-11-30

    Horses infected with Leptospira interrogans present several clinical disorders, one of them being recurrent uveitis. An antigenic relationship between this bacterium and equine cornea has been described in previous studies. With the aim to make progress on defining the molecular basis and pathogenesis of equine recurrent uveitis, here we describe the cloning of one DNA fragment from a Leptospira interrogans serovar pomona genomic lambda gt11 library. Although there are references of transcription of leptospiral genes in E. coli from their own leptospiral promoters, in this recombinant construction the leptospiral DNA was located under the control of lacZ promoter since no expression could be detected in the absence of IPTG. This clone, isolated by expression screening with polyclonal serum raised against equine corneal proteins, encodes a 90 kDa protein of L. interrogans which crossreacts with equine cornea as proved Western-blotting. Antibodies directed against this leptospiral protein strongly recognised a 66 kDa equine corneal protein, one of those recognised by an anti-equine cornea serum. Our findings suggest that an immune response to 90 kDa protein participates in pathogenesis of equine uveitis.

  15. A protein that interacts with members of the nuclear hormone receptor family: identification and cDNA cloning.

    PubMed Central

    Zeiner, M; Gehring, U

    1995-01-01

    In search of proteins which interact with activated steroid hormone receptors, we screened a human liver lambda gt11 expression library with the glucocorticoid receptor. We identified and cloned a cDNA sequence of 1322 bp that encodes a protein of 274 aa. This protein consists predominantly of hydrophilic amino acids and contains a putative bipartite nuclear localization signal. The in vitro translated receptor-associating protein runs in SDS/polyacrylamide gels with an apparent molecular mass of 46 kDa. By use of the bacterially expressed fusion protein with glutathione S-transferase we have found that interaction is not limited to the glucocorticoid receptor but included other nuclear receptors--most notably, the estrogen and thyroid receptors. Binding also occurs with the glucocorticoid receptor complexed with the antiglucocorticoid RU 38486, with the estrogen receptor complexed with the antiestrogen 4-hydroxytamoxifen or ICI 164,384, and even with receptors not complexed with ligand. Association with steroid hormone receptors depends on prior receptor activation--i.e., release from heat shock proteins. The sequence identified here appears to be a general partner protein for nuclear hormone receptors, with the gene being expressed in a variety of mammalian tissues. Images Fig. 2 Fig. 3 Fig. 4 PMID:8524784

  16. Refractive index and birefringence of 2H silicon carbide.

    NASA Technical Reports Server (NTRS)

    Powell, J. A.

    1972-01-01

    Measurement of the refractive indices of 2H SiC over the wavelength range from 435.8 to 650.9 nm by the method of minimum deviation. A curve fit of the experimental data to the Cauchy dispersion equation yielded, for the ordinary index, n sub zero = 2.5513 + 25,850/lambda squared + 8.928 x 10 to the 8th power/lambda to the 4th power and, for the extraordinary index, n sub e = 2.6161 + 28,230/lambda squared + 11.490 x 10 to the 8th power/lambda to the 4th power when lambda is expressed in nm. The estimated error (standard deviation) in these values is plus or minus 0.0006 for n sub zero and plus or minus 0.0009 for n sub e. The birefringence calculated from these expressions is about 20% less than previously published values.

  17. Performance and Value of IFN-Lambda3 and IFN-Lambda4 Genotyping in Patients with Chronic Hepatitis C (CHC) Genotype 2/3 in a Real World Setting

    PubMed Central

    Susser, Simone; Rogalska-Taranta, Magdalena; Petersen, Jörg; Böker, Klaus H. W.; Grigorian, Natalia; Link, Ralph; Naumann, Uwe; John, Christine; Lueth, Stefan; Malfertheiner, Peter; Manns, Michael P.; Wedemeyer, Heiner; Sarrazin, Christoph; Cornberg, Markus

    2015-01-01

    Background SNPs near the interferon lambda (IFNL) 3 gene are predictors for sustained virological response (SVR) in patients with chronic hepatitis C genotype (GT) 1. In addition, a dinucleotide frame shift in ss469415590 was described, which generates IFNL4. In this study, we compared the role of IFNL4 variants with IFNL3-(rs12979860) and IFNL3-(rs8099917) on response to pegylated (PEG)-IFN and Ribavirin (RBV) in patients with chronic hepatitis C GT2/3. Methods We recruited 1006 patients with chronic hepatitis C and GT2/3 in a large German registry. A treatment with PEG-IFN and Ribavirin was started by 959 patients. We performed genotyping of IFNL3 (rs12979860, n = 726; rs8099917, n = 687) and of IFNL4 (ss469415590; n = 631). Results Both preferable IFNL3 genotypes were associated with RVR (both p<0.0001) rather than with SVR (rs12979860: p = 0.251; rs8099917: p = 0.447). Only RVR was linked to SVR in univariate and multivariate analyzes (both p<0.001). Concordance of genotyping in patients with available serum samples and EDTA blood samples (n = 259) was more than 96% for both IFNL3 SNPs. IFNL3-(rs12979860) correlated with IFNL4: 99.2% of patients with IFNL3-(rs12979860)-CC were IFNL4-(ss469415590)-TT/TT. IFNL3-(rs12979860)-CT was linked with IFNL4-(ss469415590)-TT/ΔG (98.0%) and IFNL3-(rs12979860)-TT was associated with IFNL4-(ss469415590)-ΔG/ΔG (97.6%). Conclusion IFNL3 genotyping from serum was highly efficient and can be used as an alternative if EDTA whole blood is not available. In Caucasian GT2/3 patients genotyping for INFL4-(ss469415590) does not lead to additional information for the decision-making process. Importantly, IFNL3 SNPs were not associated with SVR but with RVR. Even in the era of new direct acting antiviral (DAA) therapies, IFNL3 testing may therefore still be considered for naïve GT2/3 patients to decide if dual Peg-IFN/RBV therapy is an option in resource limited regions. PMID:26699619

  18. Performance and Value of IFN-Lambda3 and IFN-Lambda4 Genotyping in Patients with Chronic Hepatitis C (CHC) Genotype 2/3 in a Real World Setting.

    PubMed

    Wiegand, Steffen B; Heidrich, Benjamin; Susser, Simone; Rogalska-Taranta, Magdalena; Petersen, Jörg; Böker, Klaus H W; Grigorian, Natalia; Link, Ralph; Naumann, Uwe; John, Christine; Lueth, Stefan; Malfertheiner, Peter; Manns, Michael P; Wedemeyer, Heiner; Sarrazin, Christoph; Cornberg, Markus

    2015-01-01

    SNPs near the interferon lambda (IFNL) 3 gene are predictors for sustained virological response (SVR) in patients with chronic hepatitis C genotype (GT) 1. In addition, a dinucleotide frame shift in ss469415590 was described, which generates IFNL4. In this study, we compared the role of IFNL4 variants with IFNL3-(rs12979860) and IFNL3-(rs8099917) on response to pegylated (PEG)-IFN and Ribavirin (RBV) in patients with chronic hepatitis C GT2/3. We recruited 1006 patients with chronic hepatitis C and GT2/3 in a large German registry. A treatment with PEG-IFN and Ribavirin was started by 959 patients. We performed genotyping of IFNL3 (rs12979860, n = 726; rs8099917, n = 687) and of IFNL4 (ss469415590; n = 631). Both preferable IFNL3 genotypes were associated with RVR (both p<0.0001) rather than with SVR (rs12979860: p = 0.251; rs8099917: p = 0.447). Only RVR was linked to SVR in univariate and multivariate analyzes (both p<0.001). Concordance of genotyping in patients with available serum samples and EDTA blood samples (n = 259) was more than 96% for both IFNL3 SNPs. IFNL3-(rs12979860) correlated with IFNL4: 99.2% of patients with IFNL3-(rs12979860)-CC were IFNL4-(ss469415590)-TT/TT. IFNL3-(rs12979860)-CT was linked with IFNL4-(ss469415590)-TT/ΔG (98.0%) and IFNL3-(rs12979860)-TT was associated with IFNL4-(ss469415590)-ΔG/ΔG (97.6%). IFNL3 genotyping from serum was highly efficient and can be used as an alternative if EDTA whole blood is not available. In Caucasian GT2/3 patients genotyping for INFL4-(ss469415590) does not lead to additional information for the decision-making process. Importantly, IFNL3 SNPs were not associated with SVR but with RVR. Even in the era of new direct acting antiviral (DAA) therapies, IFNL3 testing may therefore still be considered for naïve GT2/3 patients to decide if dual Peg-IFN/RBV therapy is an option in resource limited regions.

  19. [The expression of interferon-lambda1 in CHO cell].

    PubMed

    Yuan, Wu-Mei; Ma, Fen-Lian; Zhang, Qian; Zheng, Wen-Zhi; Zheng, Li-Shu

    2013-06-01

    To construct the eukaryotic expression vector PCI-dhfr-lambda1 and PCI-dhfr-SP163-lambda1 which linked the enhancer SP163 with interferon lambda1. Then express the interferon lambda1 in CHO (dhfr-) cells. Using PCR method to introduce the restriction enzyme sites and through the fusion PCR binding the enhancer with the interferon Lambda1. After sequenced, lambda1 and SP163-lambda1 was inserted into PCI-dhfr forming the expression vector PCI-dhfr-lambda1 and PCI-dhfr-SP163-lambda1 which was constructed successfully confirming by sequencing. Then the expressing vectors were transfected into CHO (dhfr-) cells using liposome transfection method and interferon lambda1 protein was assayed with indirect immunofluorescence and Western Blot. Using cytopathic effect inhibition evaluated the antiviral activity of interferon lambda1. Successfully constructing the eukaryotic expression vectors of interferon lambda and the vectors could express interferon lambda1. The result of immunofluorescence showed the enhancer developed the expression of interferon lambda1. Detecting the interferon lambda1 in CHO (dhfr-) cells after transfecting 48 hour using Western Blot. The cytopathic effect inhibition showed the expressed interferon lambda1 has the antiviral activity. Successfully expressed the interferon lambda1 in CHO (dhfr-) cells and the protein possesses antiviral activity, which may supply a valuable basis for building the stable cell line of interferon lambda1.

  20. Five-Body Cluster Structure of the Double-{Lambda} Hypernucleus {sub {Lambda}{Lambda}}{sup 11}Be

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

    Hiyama, E.; Kamimura, M.; Yamamoto, Y.

    2010-05-28

    Energy levels of the double {Lambda} hypernucleus, {sub {Lambda}{Lambda}}{sup 11}Be are calculated within the framework of a {alpha}{alpha}n{Lambda}{Lambda} five-body model. Interactions between constituent particles are determined so as to reproduce reasonably the observed low-energy properties of the {alpha}{alpha}, {alpha}{alpha}n nuclei and the existing data for {Lambda}-binding energies of the {alpha}{Lambda}, {alpha}{alpha}{Lambda}, {alpha}n{Lambda}, and {alpha}{alpha}n{Lambda} systems. An effective {Lambda}{Lambda} interaction is constructed so as to reproduce, within the {alpha}{Lambda}{Lambda} three-body model, the B{sub {Lambda}{Lambda}}of {sub {Lambda}{Lambda}}{sup 6}He, which was extracted from the emulsion experiment, the NAGARA event. With no adjustable parameters for the {alpha}{alpha}n{Lambda}{Lambda} system, B{sub {Lambda}{Lambda}}of the ground and boundmore » excited states of {sub {Lambda}{Lambda}}{sup 11}Be are calculated with the Gaussian expansion method. The Hida event, recently observed at KEK-E373 experiment, is interpreted as an observation of the ground state of the {sub {Lambda}{Lambda}}{sup 11}Be.« less

  1. Rearrangement and expression of the human {Psi}C{lambda}6 gene segment results in a surface Ig receptor with a truncated light chain constant region

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

    Stiernholm, N.B.J.; Verkoczy, L.K.; Berinstein, N.L.

    1995-05-01

    The constant region of the human Ig{lambda} locus consists of seven tandemly organized J-C gene segments. Although it has been established that the J-C{lambda}1, J-C{lambda}2, J-C{lambda}3, and J-C{lambda}7 gene segments are functional, and code for the four distinct Ig{lambda} isotypes found in human serum, the J-C{lambda}4, J-C{lambda}5, and J-C{lambda}6 gene segments are generally considered to be pseudogenes. Although one example of a functional J-C{lambda}6 gene segment has been documented, in the majority of cases, J-C{lambda}6 is rendered nonfunctional by virtue of a single duplication of four nucleotides, creating a premature translational arrest. We show here that rearrangements to the J-C{lambda}6more » gene segment do occur, and that such a rearrangement encodes an Ig{lambda} protein that lacks the terminal end of the constant region. We also show that this truncated protein is expressed on the surface with the IgH chain, creating an unusual surface Ig (sIg) receptor (sIg{triangle}CL). Cells that express this receptor on the surface do so at significantly reduced levels compared with clonally related variants, which express sIg receptors with conventional Ig{lambda} L chains. However, the effects of sIg cross-linking on tyrosine phosphorylation and surface expression of the CD25 and CD71 Ags are similar in cells that express conventional sIg receptors and in those that express sIg{triangle}CL receptors, suggesting that the latter could possibly function as an Ag receptor. 35 refs., 7 figs.« less

  2. The hit problem for symmetric polynomials over the Steenrod algebra

    NASA Astrophysics Data System (ADS)

    Janfada, A. S.; Wood, R. M. W.

    2002-09-01

    We cite [18] for references to work on the hit problem for the polynomial algebra P(n) = [open face F]2[x1, ;…, xn] = [oplus B: plus sign in circle]d[gt-or-equal, slanted]0 Pd(n), viewed as a graded left module over the Steenrod algebra [script A] at the prime 2. The grading is by the homogeneous polynomials Pd(n) of degree d in the n variables x1, …, xn of grading 1. The present article investigates the hit problem for the [script A]-submodule of symmetric polynomials B(n) = P(n)[sum L: summation operator]n , where [sum L: summation operator]n denotes the symmetric group on n letters acting on the right of P(n). Among the main results is the symmetric version of the well-known Peterson conjecture. For a positive integer d, let [mu](d) denote the smallest value of k for which d = [sum L: summation operator]ki=1(2[lambda]i[minus sign]1), where [lambda]i [gt-or-equal, slanted] 0.

  3. [Cloning of Chinese Banna minipig inbred-line alpha1,3-galactosyltransferase gene and construction of its recombinant eukaryotic expression vector].

    PubMed

    Zhu, Shengming; Wang, Yanping; Zheng, Hong; Cheng, Jingqiu; Lu, Yanrong; Zeng, Yangzhi; Wang, Yu; Wang, Zhu

    2009-04-01

    This study sought to clone Chinese Banna minipig inbred-line (BMI) alpha1,3-galactosyltransferase (alpha1,3-GT) gene and construct its recombinant eukaryotic expression vector. Total RNA was isolated from BMI liver. Full length cDNA of alpha1,3-GT gene was amplified by RT-PCR and cloned into pMD18-T vector to sequence. Subsequently, alpha1,3-GT gene was inserted into pEGFP-N1 to construct eukaryotic expression vector pEGFP-N1-GT. Then the reconstructed plasmid pEGFP-N1-GT was transiently transfected into human lung cancer cell line A549. The expression of alpha1,3-GT mRNA in transfected cells was detected by RT-PCR. FITC-BS-IB4 lectin was used in the direct immunofluorescence method, which was performed to observe the alpha-Gal synthesis function of BMI alpha1,3-GT in transfected cells. The results showed that full length of BMI alpha1,3-GT cDNA was 1116 bp. BMI alpha1,3-GT cDNA sequence was highly homogenous with those of mouse and bovine, and was exactly the same as the complete sequence of those of swine, pEGFP-N1-GT was confirmed by enzyme digestion and PCR. The expression of alpha1,3-GT mRNA was detected in A549 cells transfected by pEGFP-N1-GT. The expression of alpha-Gal was observed on the membrane of A549 cells transfected by pEGFP-N1-GT. Successful cloning of BMI alpha1,3-GT cDNA and construction of its eukaryotic expression vector have established a foundation for further research and application of BMI alpha1,3-GT in the fields of xenotransplantation and immunological therapy of cancer.

  4. The 87-kD A gamma-globin enhancer-binding protein is a product of the HOXB2(HOX2H) locus.

    PubMed

    Sengupta, P K; Lavelle, D E; DeSimone, J

    1994-03-01

    Developmental regulation of globin gene expression may be controlled by developmental stage-specific nuclear proteins that influence interactions between the locus control region and local regulatory sequences near individual globin genes. We previously isolated an 87-kD nuclear protein from K562 cells that bound to DNA sequences in the beta-globin locus control region, gamma-globin promoter, and A gamma-globin enhancer. The presence of this protein in fetal globin-expressing cells and its absence in adult globin-expressing cells suggested that it may be a developmental stage-specific factor. A lambda gt11 K562 cDNA clone encoding a portion of the HOXB2 (formerly HOX2H) homeobox gene was isolated on the basis of the ability of its beta-galactosidase fusion protein to bind to the same DNA sequences as the 87-kD K562 protein. Because no other relationship had been established between the 87-kD K562 protein and the HOXB2 protein other than their ability to bind ot the same DNA sequences, we have investigated whether the two proteins are related antigenically. Our data show that antisera produced against the HOXB2-beta-gal fusion protein and a synthetic HOXB2 decapeptide react specifically with an 87-kD protein from K562 nuclear extract, showing that the 87-kD K562 nuclear protein is a product of the HOXB2 locus, and is the first demonstration of cellular HOXB2 protein.

  5. Gibberellin (GA3) enhances cell wall invertase activity and mRNA levels in elongating dwarf pea (Pisum sativum) shoots

    NASA Technical Reports Server (NTRS)

    Wu, L. L.; Mitchell, J. P.; Cohn, N. S.; Kaufman, P. B.

    1993-01-01

    The invertase (EC 3.2.1.26) purified from cell walls of dwarf pea stems to homogeneity has a molecular mass of 64 kilodaltons (kD). Poly(A)+RNA was isolated from shoots of dwarf pea plants, and a cDNA library was constructed using lambda gt11 as an expression vector. The expression cDNA library was screened with polyclonal antibodies against pea cell wall invertase. One invertase cDNA clone was characterized as a full-length cDNA with 1,863 base pairs. Compared with other known invertases, one homologous region in the amino acid sequence was found. The conserved motif, Asn-Asp-Pro-Asn-Gly, is located near the N-terminal end of invertase. Northern blot analysis showed that the amount of invertase mRNA (1.86 kb) was rapidly induced to a maximal level 4 h after GA3 treatment, then gradually decreased to the control level. The mRNA level at 4 h in GA3-treated peas was fivefold higher than that of the control group. The maximal increase in activity of pea cell wall invertase elicited by GA3 occcured at 8 h after GA3 treatment. This invertase isoform was shown immunocytochemically to be localized in the cell walls, where a 10-fold higher accumulation occurred in GA3-treated tissue compared with control tissue. This study indicates that the expression of the pea shoot cell-wall invertase gene could be regulated by GA3 at transcriptional and/or translational levels.

  6. The VBP and a1/EBP leucine zipper factors bind overlapping subsets of avian retroviral long terminal repeat CCAAT/enhancer elements.

    PubMed

    Smith, C D; Baglia, L A; Curristin, S M; Ruddell, A

    1994-10-01

    Two long terminal repeat (LTR) enhancer-binding proteins which may regulate high rates of avian leukosis virus (ALV) LTR-enhanced c-myc transcription during bursal lymphomagenesis have been identified (A. Ruddell, M. Linial, and M. Groudine, Mol. Cell. Biol. 9:5660-5668, 1989). The genes encoding the a1/EBP and a3/EBP binding factors were cloned by expression screening of a lambda gt11 cDNA library from chicken bursal lymphoma cells. The a1/EBP cDNA encodes a novel leucine zipper transcription factor (W. Bowers and A. Ruddell, J. Virol. 66:6578-6586, 1992). The partial a3/EBP cDNA clone encodes amino acids 84 to 313 of vitellogenin gene-binding protein (VBP), a leucine zipper factor that binds the avian vitellogenin II gene promoter (S. Iyer, D. Davis, and J. Burch, Mol. Cell. Biol. 11:4863-4875, 1991). Multiple VBP mRNAs are expressed in B cells in a pattern identical to that previously observed for VBP in other cell types. The LTR-binding activities of VBP, a1/EBP, and B-cell nuclear extract protein were compared and mapped by gel shift, DNase I footprinting, and methylation interference assays. The purified VBP and a1/EBP bacterial fusion proteins bind overlapping but distinct subsets of CCAAT/enhancer elements in the closely related ALV and Rous sarcoma virus (RSV) LTR enhancers. Protein binding to these CCAAT/enhancer elements accounts for most of the labile LTR enhancer-binding activity observed in B-cell nuclear extracts. VBP and a1/EBP could mediate the high rates of ALV and RSV LTR-enhanced transcription in bursal lymphoma cells and many other cell types.

  7. Anti-liver-kidney microsome antibody type 1 recognizes human cytochrome P450 db1.

    PubMed

    Gueguen, M; Yamamoto, A M; Bernard, O; Alvarez, F

    1989-03-15

    Anti-liver-kidney microsome antibody type 1 (LKM1), present in the sera of a group of children with autoimmune hepatitis, was recently shown to recognize a 50 kDa protein identified as rat liver cytochromes P450 db1 and db2. High homology between these two members of the rat P450 IID subfamily and human P450 db1 suggested that anti-LKM1 antibody is directed against this human protein. To test this hypothesis, a human liver cDNA expression library in phage lambda GT-11 was screened using rat P450 db1 cDNA as a probe. Two human cDNA clones were found to be identical to human P450 db1 by restriction mapping. Immunoblot analysis using as antigen, the purified fusion protein from one of the human cDNA clones showed that only anti-LKM1 with anti-50 kDa reactivity recognized the fusion protein. This fusion protein was further used to develop an ELISA test that was shown to be specific for sera of children with this disease. These results: 1) identify the human liver antigen recognized by anti-LKM1 auto-antibodies as cytochrome P450 db1, 2) allow to speculate that mutation on the human P450 db1 gene could alter its expression in the hepatocyte and make it auto-antigenic, 3) provide a simple and specific diagnostic test for this disease.

  8. Isolation of expressed sequences from the region commonly deleted in Velo-cardio-facial syndrome

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

    Sirotkin, H.; Morrow, B.; DasGupta, R.

    Velo-cardio-facial syndrome (VCFS) is a relatively common autosomal dominant genetic disorder characterized by cleft palate, cardiac abnormalities, learning disabilities and a characteristic facial dysmorphology. Most VCFS patients have interstitial deletions of 22q11 of 1-2 mb. In an effort to isolate the gene(s) responsible for VCFS we have utilized a hybrid selection protocol to recover expressed sequences from three non-overlapping YACs comprising almost 1 mb of the commonly deleted region. Total yeast genomic DNA or isolated YAC DNA was immobilized on Hybond-N filters, blocked with yeast and human ribosomal and human repetitive sequences and hybridized with a mixture of random primedmore » short fragment cDNA libraries. Six human short fragment libraries derived from total fetus, fetal brain, adult brain, testes, thymus and spleen have been used for the selections. Short fragment cDNAs retained on the filter were passed through a second round of selection and cloned into lambda gt10. cDNAs shown to originate from the YACs and from chromosome 22 are being used to isolate full length cDNAs. Three genes known to be present on these YACs, catechol-O-methyltransferase, tuple 1 and clathrin heavy chain have been recovered. Additionally, a gene related to the murine p120 gene and a number of novel short cDNAs have been isolated. The role of these genes in VCFS is being investigated.« less

  9. Itraconazole inhibits TNF-α-induced CXCL10 expression in oral fibroblasts.

    PubMed

    Ohta, K; Ishida, Y; Fukui, A; Nishi, H; Naruse, T; Takechi, M; Kamata, N

    2015-01-01

    Itraconazole (ICZ) has a broad spectrum of antifungal activity including a wide range of Candida spp. TNF-α, an inflammatory cytokine associated with Th1-mediated oral inflammatory disease, enhances inflammatory mediators, such as CXCR3-agonistic chemokines including CXCL10. We examined the anti-inflammatory potential of ICZ against TNF-α-induced chemokines in oral fibroblasts. We investigated the effects of ICZ on mRNA expressions of various TNF-α-induced chemokines in immortalized oral keratinocytes (RT7) and oral fibroblasts (GT1) using quantitative PCR analysis. Subsequently, the effects of ICZ and fluconazole (FLZ) on TNF-α-induced CXCL10 proteins in GT1 and primary fibroblasts were examined using enzyme-linked immunosorbent assays (ELISA). The effect of ICZ on signal transduction protein phosphorylation involved in CXCL10 production from TNF-α-stimulated GT1 was examined by western blotting. ICZ inhibited TNF-α-induced CXCL10 mRNA in GT1, but not RT7. Although ICZ did not affect TNF-α-induced IL-8 mRNA, the mRNAs of TNF-α-induced CXCR3-agonistic chemokines such as CXCL9 and CXCL11 were inhibited by ICZ in GT1. TNF-α-induced CXCL10 protein production in GT1 and primary fibroblasts was inhibited by ICZ, but not FLZ. Finally, ICZ inhibited TNF-α-induced phosphorylation of c-JUN, which is related to CXCL10 production by TNF-α-stimulated GT1. ICZ may be useful as therapy for Th1-mediated oral inflammatory disease. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Malignant pericytes expressing GT198 give rise to tumor cells through angiogenesis.

    PubMed

    Zhang, Liyong; Wang, Yan; Rashid, Mohammad H; Liu, Min; Angara, Kartik; Mivechi, Nahid F; Maihle, Nita J; Arbab, Ali S; Ko, Lan

    2017-08-01

    Angiogenesis promotes tumor development. Understanding the crucial factors regulating tumor angiogenesis may reveal new therapeutic targets. Human GT198 ( PSMC3IP or Hop2) is an oncoprotein encoded by a DNA repair gene that is overexpressed in tumor stromal vasculature to stimulate the expression of angiogenic factors. Here we show that pericytes expressing GT198 give rise to tumor cells through angiogenesis. GT198 + pericytes and perivascular cells are commonly present in the stromal compartment of various human solid tumors and rodent xenograft tumor models. In human oral cancer, GT198 + pericytes proliferate into GT198 + tumor cells, which migrate into lymph nodes. Increased GT198 expression is associated with increased lymph node metastasis and decreased progression-free survival in oral cancer patients. In rat brain U-251 glioblastoma xenografts, GT198 + pericytes of human tumor origin encase endothelial cells of rat origin to form mosaic angiogenic blood vessels, and differentiate into pericyte-derived tumor cells. The net effect is continued production of glioblastoma tumor cells from malignant pericytes via angiogenesis. In addition, activation of GT198 induces the expression of VEGF and promotes tube formation in cultured U251 cells. Furthermore, vaccination using GT198 protein as an antigen in mouse xenograft of GL261 glioma delayed tumor growth and prolonged mouse survival. Together, these findings suggest that GT198-expressing malignant pericytes can give rise to tumor cells through angiogenesis, and serve as a potential source of cells for distant metastasis. Hence, the oncoprotein GT198 has the potential to be a new target in anti-angiogenic therapies in human cancer.

  11. Pyrethroid insecticide lambda-cyhalothrin induces hepatic cytochrome P450 enzymes, oxidative stress and apoptosis in rats.

    PubMed

    Martínez, María-Aránzazu; Ares, Irma; Rodríguez, José-Luis; Martínez, Marta; Roura-Martínez, David; Castellano, Victor; Lopez-Torres, Bernardo; Martínez-Larrañaga, María-Rosa; Anadón, Arturo

    2018-08-01

    This study aimed to examine in rats the effects of the Type II pyrethroid lambda-cyhalothrin on hepatic microsomal cytochrome P450 (CYP) isoform activities, oxidative stress markers, gene expression of proinflammatory, oxidative stress and apoptosis mediators, and CYP isoform gene expression and metabolism phase I enzyme PCR array analysis. Lambda-cyhalothrin, at oral doses of 1, 2, 4 and 8mg/kg bw for 6days, increased, in a dose-dependent manner, hepatic activities of ethoxyresorufin O-deethylase (CYP1A1), methoxyresorufin O-demethylase (CYP1A2), pentoxyresorufin O-depentylase (CYP2B1/2), testosterone 7α- (CYP2A1), 16β- (CYP2B1), and 6β-hydroxylase (CYP3A1/2), and lauric acid 11- and 12-hydroxylase (CYP4A1/2). Similarly, lambda-cyhalothrin (4 and 8mg/kg bw, for 6days), in a dose-dependent manner, increased significantly hepatic CYP1A1, 1A2, 2A1, 2B1, 2B2, 2E1, 3A1, 3A2 and 4A1 mRNA levels and IL-1β, NFκB, Nrf2, p53, caspase-3 and Bax gene expressions. PCR array analysis showed from 84 genes examined (P<0.05; fold change>1.5), changes in mRNA levels in 18 genes: 13 up-regulated and 5 down-regulated. A greater fold change reversion than 3-fold was observed on the up-regulated ALDH1A1, CYP2B2, CYP2C80 and CYP2D4 genes. Ingenuity Pathway Analysis (IPA) groups the expressed genes into biological mechanisms that are mainly related to drug metabolism. In the top canonical pathways, Oxidative ethanol degradation III together with Fatty Acid α-oxidation may be significant pathways for lambda-cyhalothrin. Our results may provide further understanding of molecular aspects involved in lambda-cyhalothrin-induced liver injury. Copyright © 2018. Published by Elsevier B.V.

  12. Pegylated interferons Lambda-1a and alfa-2a display different gene induction and cytokine and chemokine release profiles in whole blood, human hepatocytes and peripheral blood mononuclear cells.

    PubMed

    Freeman, J; Baglino, S; Friborg, J; Kraft, Z; Gray, T; Hill, M; McPhee, F; Hillson, J; Lopez-Talavera, J C; Wind-Rotolo, M

    2014-06-01

    Pegylated interferon-lambda-1a (Lambda), a type III interferon (IFN) in clinical development for the treatment of chronic HCV infection, has shown comparable efficacy and an improved safety profile to a regimen based on pegylated IFN alfa-2a (alfa). To establish a mechanistic context for this improved profile, we investigated the ex vivo effects of Lambda and alfa on cytokine and chemokine release, and on expression of IFN-stimulated genes (ISGs) in primary human hepatocytes and peripheral blood mononuclear cells (PBMCs) from healthy subjects. Our findings were further compared with changes observed in blood analysed from HCV-infected patients treated with Lambda or alfa in clinical studies. mRNA transcript and protein expression of the IFN-λ-limiting receptor subunit was lower compared with IFN-α receptor subunits in all cell types. Upon stimulation, alfa and Lambda induced ISG expression in hepatocytes and PBMCs, although in PBMCs Lambda-induced ISG expression was modest. Furthermore, alfa and Lambda induced release of cytokines and chemokines from hepatocytes and PBMCs, although differences in their kinetics of induction were observed. In HCV-infected patients, alfa treatment induced ISG expression in whole blood after single and repeat dosing. Lambda treatment induced modest ISG expression after single dosing and showed no induction after repeat dosing. Alfa and Lambda treatment increased IP-10, iTAC, IL-6, MCP-1 and MIP-1β levels in serum, with alfa inducing higher levels of all mediators compared with Lambda. Overall, ex vivo and in vivo induction profiles reported in this analysis strongly correlate with clinical observations of fewer related adverse events for Lambda vs those typically associated with alfa. © 2014 John Wiley & Sons Ltd.

  13. Expression cloning of a gibberellin 20-oxidase, a multifunctional enzyme involved in gibberellin biosynthesis.

    PubMed Central

    Lange, T; Hedden, P; Graebe, J E

    1994-01-01

    In the biosynthetic pathway to the gibberellins (GAs), carbon-20 is removed by oxidation to give the C19-GAs, which include the biologically active plant hormones. We report the isolation of a cDNA clone encoding a GA 20-oxidase [gibberellin, 2-oxoglutarate:oxygen oxidoreductase (20-hydroxylating, oxidizing) EC 1.14.11.-] by screening a cDNA library from developing cotyledons of pumpkin (Cucurbita maxima L.) for expression of this enzyme. When mRNA from either the cotyledons or the endosperm was translated in vitro using rabbit reticulocyte lysates, the products contained GA12 20-oxidase activity. A polyclonal antiserum was raised against the amino acid sequence of a peptide released by tryptic digestion of purified GA 20-oxidase from the endosperm. A cDNA expression library in lambda gt11 was prepared from cotyledon mRNA and screened with the antiserum. The identity of positive clones was confirmed by the demonstration of GA12 20-oxidase activity in single bacteriophage plaques. Recombinant protein from a selected clone catalyzed the three-step conversions of GA12 to GA25 and of GA53 to GA17, as well as the formation of the C19-GAs, GA1, GA9, and GA20, from their respective aldehyde precursors, GA23, GA24, and GA19. The nucleotide sequence of the cDNA insert contains an open reading frame of 1158 nt encoding a protein of 386 amino acid residues. The predicted M(r) (43,321) and pI (5.3) are similar to those determined experimentally for the native GA 20-oxidase. Furthermore, the derived amino acid sequence includes sequences obtained from the N terminus and two tryptic peptides from the native enzyme. It also contains regions that are highly conserved in a group of non-heme Fe-containing dioxygenases. Images PMID:8078921

  14. Nucleotide sequence of a complementary DNA encoding pea cytosolic copper/zinc superoxide dismutase. [Pisum sativum L

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

    White, D.A.; Zilinskas, B.A.

    1991-08-01

    The authors now report the nucleotide sequence of the cytosolic Cu/Zn SOD cloned from a {lambda}gt11 cDNA library constructed from mRNA extracted from leaves of 7- to 10-d pea seedlings (Pisum sativum L.). The clone was isolated using a 22-base synthetic oligonucleotide complementary to the amino acid sequence CGIIGLQG. This sequence, found at the protein's carboxy terminus, is highly conserved among plant cytosolic Cu/Zn SODs but not chloroplastic Cu/Zn SODs. The 738-base pair sequence contains an open reading frame specifying 152 codons and a predicted M{sub r} of 18,024 D. The deduced amino acid sequence is highly homologous (79-82% identity)more » with the sequences of other known plant cytosolic Cu/Zn SODs but less highly conserved (63-65%) when compared with several chloroplastic Cu/Zn SODs including pea (10).« less

  15. A thermostable Gloeophyllum trabeum xylanase with potential for the brewing industry.

    PubMed

    Wang, Xiaoyu; Luo, Huiying; Yu, Wangning; Ma, Rui; You, Shuai; Liu, Weina; Hou, Lingyu; Zheng, Fei; Xie, Xiangming; Yao, Bin

    2016-05-15

    A xylanase gene of glycoside hydrolase family 10, GtXyn10, was cloned from Gloeophyllum trabeum CBS 900.73 and expressed in Pichia pastoris GS115. Purified recombinant GtXyn10 exhibited significant activities to xylan (100.0%), lichenan (11.2%), glucan (15.2%) and p-nitrophenol-β-cellobiose (18.6%), demonstrated the maximum xylanase and glucanase activities at pH 4.5-5.0 and 75°C, retained stability over the pH range of 2.0-7.5 and at 70°C, and was resistant to pepsin and trypsin, most metal ions and SDS. Multiple sequence alignment and modeled-structure analysis identified a unique Gly48 in GtXyn10, and site-directed mutagenesis of Gly48 to Lys improved the temperature optimum up to 80°C. Under simulated mashing conditions, GtXyn10 (80U) reduced the mash viscosity by 12.8% and improved the filtration rate by 31.3%. All these properties above make GtXyn10 attractive for potential applications in the feed and brewing industries. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. A Novel Glucosylation Reaction on Anthocyanins Catalyzed by Acyl-Glucose–Dependent Glucosyltransferase in the Petals of Carnation and Delphinium[C][W

    PubMed Central

    Matsuba, Yuki; Sasaki, Nobuhiro; Tera, Masayuki; Okamura, Masachika; Abe, Yutaka; Okamoto, Emi; Nakamura, Haruka; Funabashi, Hisakage; Takatsu, Makoto; Saito, Mikako; Matsuoka, Hideaki; Nagasawa, Kazuo; Ozeki, Yoshihiro

    2010-01-01

    Glucosylation of anthocyanin in carnations (Dianthus caryophyllus) and delphiniums (Delphinium grandiflorum) involves novel sugar donors, aromatic acyl-glucoses, in a reaction catalyzed by the enzymes acyl-glucose–dependent anthocyanin 5(7)-O-glucosyltransferase (AA5GT and AA7GT). The AA5GT enzyme was purified from carnation petals, and cDNAs encoding carnation Dc AA5GT and the delphinium homolog Dg AA7GT were isolated. Recombinant Dc AA5GT and Dg AA7GT proteins showed AA5GT and AA7GT activities in vitro. Although expression of Dc AA5GT in developing carnation petals was highest at early stages, AA5GT activity and anthocyanin accumulation continued to increase during later stages. Neither Dc AA5GT expression nor AA5GT activity was observed in the petals of mutant carnations; these petals accumulated anthocyanin lacking the glucosyl moiety at the 5 position. Transient expression of Dc AA5GT in petal cells of mutant carnations is expected to result in the transfer of a glucose moiety to the 5 position of anthocyanin. The amino acid sequences of Dc AA5GT and Dg AA7GT showed high similarity to glycoside hydrolase family 1 proteins, which typically act as β-glycosidases. A phylogenetic analysis of the amino acid sequences suggested that other plant species are likely to have similar acyl-glucose–dependent glucosyltransferases. PMID:20971893

  17. The VPH1 gene encodes a 95-kDa integral membrane polypeptide required for in vivo assembly and activity of the yeast vacuolar H(+)-ATPase.

    PubMed

    Manolson, M F; Proteau, D; Preston, R A; Stenbit, A; Roberts, B T; Hoyt, M A; Preuss, D; Mulholland, J; Botstein, D; Jones, E W

    1992-07-15

    Yeast vacuolar acidification-defective (vph) mutants were identified using the pH-sensitive fluorescence of 6-carboxyfluorescein diacetate (Preston, R. A., Murphy, R. F., and Jones, E. W. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 7027-7031). Vacuoles purified from yeast bearing the vph1-1 mutation had no detectable bafilomycin-sensitive ATPase activity or ATP-dependent proton pumping. The peripherally bound nucleotide-binding subunits of the vacuolar H(+)-ATPase (60 and 69 kDa) were no longer associated with vacuolar membranes yet were present in wild type levels in yeast whole cell extracts. The VPH1 gene was cloned by complementation of the vph1-1 mutation and independently cloned by screening a lambda gt11 expression library with antibodies directed against a 95-kDa vacuolar integral membrane protein. Deletion disruption of the VPH1 gene revealed that the VPH1 gene is not essential for viability but is required for vacuolar H(+)-ATPase assembly and vacuolar acidification. VPH1 encodes a predicted polypeptide of 840 amino acid residues (molecular mass 95.6 kDa) and contains six putative membrane-spanning regions. Cell fractionation and immunodetection demonstrate that Vph1p is a vacuolar integral membrane protein that co-purifies with vacuolar H(+)-ATPase activity. Multiple sequence alignments show extensive homology over the entire lengths of the following four polypeptides: Vph1p, the 116-kDa polypeptide of the rat clathrin-coated vesicles/synaptic vesicle proton pump, the predicted polypeptide encoded by the yeast gene STV1 (Similar To VPH1, identified as an open reading frame next to the BUB2 gene), and the TJ6 mouse immune suppressor factor.

  18. Shell-model predictions for Lambda Lambda hypernuclei

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

    Gal, A.; Millener, D.

    2011-06-02

    It is shown how the recent shell-model determination of {Lambda}N spin-dependent interaction terms in {Lambda} hypernuclei allows for a reliable deduction of {Lambda}{Lambda} separation energies in {Lambda}{Lambda} hypernuclei across the nuclear p shell. Comparison is made with the available data, highlighting {sub {Lambda}{Lambda}}{sup 11}Be and {sub {Lambda}{Lambda}}{sup 12}Be which have been suggested as possible candidates for the KEK-E373 HIDA event.

  19. Characterization and expression analysis of a banana gene encoding 1-aminocyclopropane-1-carboxylate oxidase.

    PubMed

    Huang, P L; Do, Y Y; Huang, F C; Thay, T S; Chang, T W

    1997-04-01

    A cDNA encoding the banana 1-aminocyclopropane-1-carboxylate (ACC) oxidase has previously been isolated from a cDNA library that was constructed by extracting poly(A)+ RNA from peels of ripening banana. This cDNA, designated as pMAO2, has 1,199 bp and contains an open reading frame of 318 amino acids. In order to identify ripening-related promoters of the banana ACC oxidase gene, pMAO2 was used as a probe to screen a banana genomic library constructed in the lambda EMBL3 vector. The banana ACC oxidase MAO2 gene has four exons and three introns, with all of the boundaries between these introns and exons sharing a consensus dinucleotide sequence of GT-AG. The expression of MAO2 gene in banana begins after the onset of ripening (stage 2) and continuous into later stages of the ripening process. The accumulation of MAO2 mRNA can be induced by 1 microliter/l exogenous ethylene, and it reached steady state level when 100 microliters/l exogenous ethylene was present.

  20. {Lambda}K*{Lambda}(1116) photoproduction and nucleon resonances

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

    Kim, Sang-Ho; Kim, Hyun-Chul; Nam, Seung-il

    2011-10-21

    In this presentation, we report our recent studies on the {Lambda}K*{Lambda}(1116) photoproduction off the proton target, using the tree-level Born approximation, via the effective Lagrangian approach. In addition, we include the nine (three- or four-star confirmed) nucleon resonances below the threshold {radical}(s{sub th}){approx_equal}2008 MeV, to interpret the discrepancy between the experiment and previous theoretical studies, in the vicinity of the threshold region. From the numerical studies, we observe that the S{sub 11}(1535) and S11(1650) play an important role for the cross-section enhancement near the {radical}(s{sub th}). It also turns out that, in order to reproduce the data, we have themore » vector coupling constants gK*S{sub 11}(1535){Lambda} = (7.0{approx}9.0) and gK*S{sub 11}(1650){Lambda} (5.0{approx}6.0).« less

  1. Isolation of a complementary DNA clone for thyroid microsomal antigen. Homology with the gene for thyroid peroxidase.

    PubMed Central

    Seto, P; Hirayu, H; Magnusson, R P; Gestautas, J; Portmann, L; DeGroot, L J; Rapoport, B

    1987-01-01

    The thyroid microsomal antigen (MSA) in autoimmune thyroid disease is a protein of approximately 107 kD. We screened a human thyroid cDNA library constructed in the expression vector lambda gt11 with anti-107-kD monoclonal antibodies. Of five clones obtained, the recombinant beta-galactosidase fusion protein from one clone (PM-5) was confirmed to react with the monoclonal antiserum. The complementary DNA (cDNA) insert from PM-5 (0.8 kb) was used as a probe on Northern blot analysis to estimate the size of the mRNA coding for the MSA. The 2.9-kb messenger RNA (mRNA) species observed was the same size as that coding for human thyroid peroxidase (TPO). The probe did not bind to human liver mRNA, indicating the thyroid-specific nature of the PM-5-related mRNA. The nucleotide sequence of PM-5 (842 bp) was determined and consisted of a single open reading frame. Comparison of the nucleotide sequence of PM-5 with that presently available for pig TPO indicates 84% homology. In conclusion, a cDNA clone representing part of the microsomal antigen has been isolated. Sequence homology with porcine TPO, as well as identity in the size of the mRNA species for both the microsomal antigen and TPO, indicate that the microsomal antigen is, at least in part, TPO. Images PMID:3654979

  2. Expression of calmodulin mRNA in rat olfactory neuroepithelium.

    PubMed

    Biffo, S; Goren, T; Khew-Goodall, Y S; Miara, J; Margolis, F L

    1991-04-01

    A calmodulin (CaM) cDNA was isolated by differential hybridization screening of a lambda gt10 library prepared from rat olfactory mucosa. This cDNA fragment, containing most of the open reading frame of the rat CaMI gene, was subcloned and used to characterize steady-state expression of CaM mRNA in rat olfactory neuroepithelium and bulb. Within the bulb mitral cells are the primary neuronal population expressing CaM mRNA. The major CaM mRNA expressed in the olfactory mucosa is 1.7 kb with smaller contributions from mRNAs of 4.0 and 1.4 kb. CaM mRNA was primarily associated with the olfactory neurons and, despite the cellular complexity of the tissue and the known involvement of CaM in diverse cellular processes, was only minimally evident in sustentacular cells, gland cells or respiratory epithelium. Following bulbectomy CaM mRNA declines in the olfactory neuroepithelium as does olfactory marker protein (OMP) mRNA. In contrast to the latter, CaM mRNA makes a partial recovery by one month after surgery. These results, coupled with those from in situ hybridization, indicate that CaM mRNA is expressed in both mature and immature olfactory neurons. The program regulating CaM gene expression in olfactory neurons is distinct from those controlling expression of B50/GAP43 in immature, or OMP in mature, neurons respectively.

  3. Initiation au Lambda-Calcul (An Initiation into Lambda Calculus)

    DTIC Science & Technology

    1989-07-15

    un style do preuve par r~curronce, qui est ’analogue do la r6currence structurelle traditionnelle des structuros libros , mais tenant compte du fait quo...pas libro dans M. La th6orie do la OT-r6duction nWest pas aussi 6l6ganto quo cello do la 0-r6duction souls, A causo do I’ambiguil:6 dos expressions do...donne 16 typo des variables libros . Pour los variables lies, 11 est usuet do dclarer tour typo done un champ suppl6mentaire do lop6ratour

  4. Interferon lambda 1-3 expression in infants hospitalized for RSV or HRV associated bronchiolitis.

    PubMed

    Selvaggi, Carla; Pierangeli, Alessandra; Fabiani, Marco; Spano, Lucia; Nicolai, Ambra; Papoff, Paola; Moretti, Corrado; Midulla, Fabio; Antonelli, Guido; Scagnolari, Carolina

    2014-05-01

    The airway expression of type III interferons (IFNs) was evaluated in infants hospitalized for respiratory syncytial virus (RSV) or rhinovirus (HRV) bronchiolitis. As an additional objective we sought to determine whether a different expression of IFN lambda 1-3 was associated with different harboring viruses, the clinical course of bronchiolitis or with the levels of well established IFN stimulated genes (ISGs), such as mixovirus resistance A (MxA) and ISG56. The analysis was undertaken in 118 infants with RSV or HRV bronchiolitis. Nasopharyngeal washes were collected for virological studies and molecular analysis of type III IFN responses. RSV elicited higher levels of IFN lambda subtypes when compared with HRV. A similar expression of type III IFN was found in RSVA or RSVB infected infants and in those infected with HRVA or HRVC viruses. Results also indicate that IFN lambda 1 and IFN lambda 2-3 levels were correlated with each other and with MxA and ISG56-mRNAs. In addition, a positive correlation exists between the IFN lambda1 levels and the clinical score index during RSV infection. In particular, higher IFN lambda 1 levels are associated to an increase of respiratory rate. These findings show that differences in the IFN lambda 1-3 levels in infants with RSV or HRV infections are present and that the expression of IFN lambda 1 correlates with the severity of RSV bronchiolitis. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  5. Further improvements of a new model for turbulent convection in stars

    NASA Technical Reports Server (NTRS)

    Canuto, V. M.; Mazzitelli, I.

    1992-01-01

    The effects of including a variable molecular weight and of using the newest opacities of Rogers and Iglesias (1991) as inputs to a recent model by Canuto and Mazzitelli (1991) for stellar turbulent convection are studied. Solar evolutionary tracks are used to conclude that the the original model for turbulence with mixing length Lambda = z, Giuli's variable Q unequal to 1 and the new opacities yields a fit to solar T(eff) within 0.5 percent. A formulation of Lambda is proposed that extends the purely nonlocal Lambda = z expression to include local effects. A new expression for Lambda is obtained which generalizes both the mixing length theory (MLT) phenomenological expression for Lambda as well as the model Lambda = z. It is argued that the MLT should now be abandoned.

  6. Glycosyltransferase Gene Expression Profiles Classify Cancer Types and Propose Prognostic Subtypes

    NASA Astrophysics Data System (ADS)

    Ashkani, Jahanshah; Naidoo, Kevin J.

    2016-05-01

    Aberrant glycosylation in tumours stem from altered glycosyltransferase (GT) gene expression but can the expression profiles of these signature genes be used to classify cancer types and lead to cancer subtype discovery? The differential structural changes to cellular glycan structures are predominantly regulated by the expression patterns of GT genes and are a hallmark of neoplastic cell metamorphoses. We found that the expression of 210 GT genes taken from 1893 cancer patient samples in The Cancer Genome Atlas (TCGA) microarray data are able to classify six cancers; breast, ovarian, glioblastoma, kidney, colon and lung. The GT gene expression profiles are used to develop cancer classifiers and propose subtypes. The subclassification of breast cancer solid tumour samples illustrates the discovery of subgroups from GT genes that match well against basal-like and HER2-enriched subtypes and correlates to clinical, mutation and survival data. This cancer type glycosyltransferase gene signature finding provides foundational evidence for the centrality of glycosylation in cancer.

  7. Antitumor activity of type I and type III interferons in BNL hepatoma model.

    PubMed

    Abushahba, Walid; Balan, Murugabaskar; Castaneda, Ismael; Yuan, Yao; Reuhl, Kenneth; Raveche, Elizabeth; de la Torre, Andrew; Lasfar, Ahmed; Kotenko, Sergei V

    2010-07-01

    Hepatocellular carcinoma (HCC) occurs most commonly secondary to cirrhosis due to chronic hepatitis C or B virus (HCV/HBV) infections. Type I interferon (IFN-alpha) treatment of chronic HCV/HBV infections reduces the incidence of HCC in cirrhotic patients. However, IFN-alpha toxicity limits its tolerability and efficacy highlighting a need for better therapeutic treatments. A recently discovered type III IFN (IFN-lambda) has been shown to possess antiviral properties against HCV and HBV in vitro. In phase I clinical trials, IFN-lambda treatment did not cause significant adverse reactions. Using a gene therapy approach, we compared the antitumor properties of IFN-alpha and IFN-lambda in a transplantable hepatoma model of HCC. BALB/c mice were inoculated with syngeneic BNL hepatoma cells, or BNL cells expressing IFN-lambda (BNL.IFN-lambda cells) or IFN-alpha (BNL.IFN-alpha cells). Despite the lack of antiproliferative activity of IFNs on BNL cells, both BNL.IFN-lambda and BNL.IFN-alpha cells displayed retarded growth kinetics in vivo. Depletion of NK cells from splenocytes inhibited splenocyte-mediated cytotoxicity, demonstrating that NK cells play a role in IFN-induced antitumor responses. However, isolated NK cells did not respond directly to IFN-lambda. There was also a marked NK cell infiltration in IFN-lambda producing tumors. In addition, IFN-lambda and, to a lesser extent, IFN-alpha enhanced immunocytotoxicity of splenocytes primed with irradiated BNL cells. Splenocyte cytotoxicity against BNL cells was dependent on IL-12 and IFN-gamma, and mediated by dendritic cells. In contrast to NK cells, isolated from spleen CD11c+ and mPDCA+ dendritic cells responded directly to IFN-lambda. The antitumor activities of IFN-lambda against hepatoma, in combination with HCV and HBV antiviral activities warrant further investigation into the clinical use of IFN-lambda to prevent HCC in HCV/HBV-infected cirrhotic patients, as well as to treat liver cancer.

  8. Active Knowledge Structures for Natural Language Processing.

    DTIC Science & Technology

    1991-01-01

    specialist belief: Assume there is a lambda-expression "(LAMBDA L) immed-type-ofL" and Z = ((LAMBDA L) immed-type-of L) ( thalassemia ), we can describe...SPEC) -> ([AVG-PERSON] -> (VAL-FOR) -> CGREEK-PLCE)3 This expresses the various levels of specialized knowledge of thalassemia , depending on

  9. Measurement of the branching fraction $${\\mathcal{B}}(\\Lambda^0_b\\rightarrow \\Lambda^+_c\\pi^-\\pi^+\\pi^-)$$ at CDF

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

    Aaltonen, T.; /Helsinki Inst. of Phys.; Alvarez Gonzalez, B.

    We report an analysis of the {Lambda}{sub b}{sup 0} {yields} {Lambda}{sub c}{sup +}{pi}{sup -}{pi}{sup +}{pi}{sup -} decay in a data sample collected by the CDF II detector at the Fermilab Tevatron corresponding to 2.4 fb{sup -1} of integrated luminosity. We reconstruct the currently largest samples of the decay modes {Lambda}{sub b}{sup 0} {yields} {Lambda}{sub c}(2595){sup +}{pi}{sup -} (with {Lambda}{sub c}(2595){sup +} {yields} {Lambda}{sub c}{sup +}{pi}{sup +}{pi}{sup -}), {Lambda}{sub b}{sup 0} {yields} {Lambda}{sub c}(2625){sup +}{pi}{sup -} (with {Lambda}{sub c}(2625){sup +} {yields} {Lambda}{sub c}{sup +}{pi}{sup +}{pi}{sup -}), {Lambda}{sub b}{sup 0} {yields} {Sigma}{sub c}(2455){sup ++}{pi}{sup -}{pi}{sup -} (with {Sigma}{sub c}(2455){sup ++} {yields} {Lambda}{submore » c}{sup +}{pi}{sup +}), and {Lambda}{sub b}{sup 0} {yields} {Sigma}{sub c}(2455)0{pi}{sup +}{pi}{sup -} (with {Sigma}{sub c}(2455)0 {yields} {Lambda}{sub c}{sup +}{pi}{sup -}) and measure the branching fractions relative to the {Lambda}{sub b}{sup 0} {yields} {Lambda}{sub c}{sup +}{pi}{sup -} branching fraction. We measure the ratio {Beta}({Lambda}{sub b}{sup 0} {yields} {Lambda}{sub c}{sup +}{pi}{sup -}{pi}{sup +}{pi}{sup -})/ {Beta}({Lambda}{sub b}{sup 0} {yields} {Lambda}{sub c}{sup +}{pi}{sup -})=3.04 {+-} 0.33(stat){sub -0.55}{sup +0.70}(syst) which is used to derive {Beta}({Lambda}{sub b}{sup 0} {yields} {Lambda}{sub c}{sup +}{pi}{sup -}{pi}{sup +}{pi}{sup -})=(26.8{sub -11.2}{sup +11.9}) x 10{sup -3}.« less

  10. In vitro evidence of glucose-induced toxicity in GnRH secreting neurons: high glucose concentrations influence GnRH secretion, impair cell viability, and induce apoptosis in the GT1-1 neuronal cell line.

    PubMed

    Pal, Lubna; Chu, Hsiao-Pai; Shu, Jun; Topalli, Ilir; Santoro, Nanette; Karkanias, George

    2007-10-01

    To evaluate for direct toxic effects of high glucose concentrations on cellular physiology in GnRH secreting immortalized GT1-1 neurons. Prospective experimental design. In vitro experimental model using a cell culture system. GT1-1 cells were cultured in replicates in media with two different glucose concentrations (450 mg/dL and 100 mg/dL, respectively) for varying time intervals (24, 48, and 72 hours). Effects of glucose concentrations on GnRH secretion by the GT1-1 neurons were evaluated using a static culture model. Cell viability, cellular apoptosis, and cell cycle events in GT1-1 neurons maintained in two different glucose concentrations were assessed by flow cytometry (fluorescence-activated cell sorter) using Annexin V-PI staining. Adverse influences of high glucose concentrations on GnRH secretion and cell viability were noted in cultures maintained in high glucose concentration (450 mg/dL) culture medium for varying time intervals. A significantly higher percentage of cells maintained in high glucose concentration medium demonstrated evidence of apoptosis by a fluorescence-activated cell sorter. We provide in vitro evidence of glucose-induced cellular toxicity in GnRH secreting GT1-1 neurons. Significant alterations in GnRH secretion, reduced cell viability, and a higher percentage of apoptotic cells were observed in GT1-1 cells maintained in high (450 mg/dL) compared with low (100 mg/dL) glucose concentration culture medium.

  11. Multi-substrate flavonol O-glucosyltransferases from strawberry (Fragaria×ananassa) achene and receptacle

    PubMed Central

    Griesser, Markus; Vitzthum, Florian; Fink, Barbara; Bellido, Mari Luz; Raasch, Constanze; Munoz-Blanco, Juan; Schwab, Wilfried

    2008-01-01

    In an effort to characterize fruit ripening-related genes functionally, two glucosyltransferases, FaGT6 and FaGT7, were cloned from a strawberry (Fragaria×ananassa) cDNA library and the full-length open reading frames were amplified by rapid amplification of cDNA ends. FaGT6 and FaGT7 were expressed heterologously as fusion proteins in Escherichia coli and target protein was purified using affinity chromatography. Both recombinant enzymes exhibited a broad substrate tolerance in vitro, accepting numerous flavonoids, hydroxycoumarins, and naphthols. FaGT6 formed 3-O-glucosides and minor amounts of 7-O-, 4′-O-, and 3′-O-monoglucosides and one diglucoside from flavonols such as quercetin. FaGT7 converted quercetin to the 3-O-glucoside and 4′-O-glucoside and minor levels of the 7- and 3′-isomers but formed no diglucoside. Gene expression studies showed that both genes are strongly expressed in achenes of small-sized green fruits, while the expression levels were generally lower in the receptacle. Significant levels of quercetin 3-O-, 7-O-, and 4′-O-glucosides, kaempferol 3-O- and 7-O-glucosides, as well as isorhamnetin 7-O-glucoside, were identified in achenes and the receptacle. In the receptacle, the expression of both genes is negatively controlled by auxin which correlates with the ripening-related gene expression in this tissue. Salicylic acid, a known signal molecule in plant defence, induces the expression of both genes. Thus, it appears that FaGT6 and FaGT7 are involved in the glucosylation of flavonols and may also participate in xenobiotic metabolism. The latter function is supported by the proven ability of strawberries to glucosylate selected unnatural substrates injected in ripe fruits. This report presents the first biochemical characterization of enzymes mainly expressed in strawberry achenes and provides the foundation of flavonoid metabolism in the seeds. PMID:18487633

  12. The Poplar GT8E and GT8F Glycosyltransferases are Functional Orthologs of Arabidopsis PARVUS Involved in Gulcuronoxylan Biosynthesis

    EPA Science Inventory

    The poplar GT8E and GT8F glycosyltransferases have previously been shown to be associated with wood formation, but their roles in the biosynthesis of wood components are not known. Here, we show that PoGT8E and PoGT8F are expressed in vessels and fibers during wood formation and ...

  13. The gap gene giant of Rhodnius prolixus is maternally expressed and required for proper head and abdomen formation.

    PubMed

    Lavore, Andrés; Pagola, Lucía; Esponda-Behrens, Natalia; Rivera-Pomar, Rolando

    2012-01-01

    The segmentation process in insects depends on a hierarchical cascade of gene activity. The first effectors downstream of the maternal activation are the gap genes, which divide the embryo in broad fields. We discovered a sequence corresponding to the leucine-zipper domain of the orthologue of the gene giant (Rp-gt) in traces from the genome of Rhodnius prolixus, a hemipteran with intermediate germ-band development. We cloned the Rp-gt gene from a normalized cDNA library and characterized its expression and function. Bioinformatic analysis of 12.5 kbp of genomic sequence containing the Rp-gt transcriptional unit shows a cluster of bona fide regulatory binding sites, which is similar in location and structure to the predicted posterior expression domain of the Drosophila orthologue. Rp-gt is expressed in ovaries and maternally supplied in the early embryo. The maternal contribution forms a gradient of scattered patches of mRNA in the preblastoderm embryo. Zygotic Rp-gt is expressed in two domains that after germ band extension are restricted to the head and the posterior growth zone. Parental RNAi shows that Rp-gt is required for proper head and abdomen formation. The head lacks mandibulary and maxillary appendages and shows reduced clypeus-labrum, while the abdomen lacks anterior segments. We conclude that Rp-gt is a gap gene on the head and abdomen and, in addition, has a function in patterning the anterior head capsule suggesting that the function of gt in hemipterans is more similar to dipterans than expected. Copyright © 2011. Published by Elsevier Inc.

  14. Fine tangled pili expressed by Haemophilus ducreyi are a novel class of pili.

    PubMed Central

    Brentjens, R J; Ketterer, M; Apicella, M A; Spinola, S M

    1996-01-01

    Haemophilus ducreyi synthesizes fine, tangled pili composed predominantly of a protein whose apparent molecular weight is 24,000 (24K). A hybridoma, 2D8, produced a monoclonal antibody (MAb) that bound to a 24K protein in H. ducreyi strains isolated from diverse geographic locations. A lambda gt11 H. ducreyi library was screened with MAb 2D8. A 3.5-kb chromosomal insert from one reactive plaque was amplified and ligated into the pCRII vector. The recombinant plasmid, designated pHD24, expressed a 24K protein in Escherichia coli INV alpha F that bound MAb 2D8. The coding sequence of the 24K gene was localized by exonuclease III digestion. The insert contained a 570-bp open reading frame, designated ftpA (fine, tangled pili). Translation of ftpA predicted a polypeptide with a molecular weight of 21.1K. The predicted N-terminal amino acid sequence of the polypeptide encoded by ftpA was identical to the N-terminal amino acid sequence of purified pilin and lacked a cleavable signal sequence. Primer extension analysis of ftpA confirmed the lack of a leader peptide. The predicted amino acid sequence lacked homology to known pilin sequences but shared homology with the sequences of E. coli Dps and Treponema pallidum antigen TpF1 or 4D, proteins which associate to form ordered rings. An isogenic pilin mutant, H. ducreyi 35000ftpA::mTn3(Cm), was constructed by shuttle mutagenesis and did not contain pili when examined by electron microscopy. We conclude that H. ducreyi synthesizes fine, tangled pili that are composed of a unique major subunit, which may be exported by a signal sequence independent mechanism. PMID:8550517

  15. Mapping of IgE-binding regions on recombinant Cyn d 1, a major allergen from Bermuda Grass Pollen (BGP).

    PubMed

    Tiwari, Ruby; Bhalla, Prem L; Singh, Mohan B

    2009-02-02

    Bermuda grass (Cynodon dactylon; subfamily Chloridoideae) is an important source of seasonal aeroallergens in warm tropical and sub-tropical areas worldwide. Improved approaches to diagnosis and therapy of allergic diseases require a thorough understanding of the structure and epitopes on the allergen molecule that are crucial for the antigen-antibody interaction. This study describes the localization of the human IgE-binding regions of the major group 1 pollen allergen Cyn d 1 from Bermuda grass. A cDNA library was constructed from Bermuda grass pollen (BGP) using a Lambda gt11 expression vector. The gene encoding the Cyn d 1 allergen was isolated by screening the library with a mouse monoclonal antibody raised against grass group 1 allergen. In order to characterize the IgE epitopes on Cyn d 1, seven overlapping fragments and three deletion mutants were cloned and over-expressed in E. coli. The recombinant fragments and deletion mutants were evaluated for their comparative IgE reactivity with sera of non atopic individuals and grass pollen allergic patients by ELISA and a dot-blot assay. Analysis of IgE binding regions by overlapping fragments and deletion mutants identified two major allergenic regions corresponding to amino acids 120-170 and 224-244. Deletion of either or both regions led to a significant reduction in IgE binding, emphasizing the importance of the C-terminal region on Cyn d 1 in epitope-IgE interaction. Anti-Cyn d 1 IgE antibodies from allergic human sera recognize two epitopes located at the C-terminal end of the molecule. These data will enable the design of improved diagnostic and therapeutic approaches for BGP hypersensitivity.

  16. A quantitative validated model reveals two phases of transcriptional regulation for the gap gene giant in Drosophila.

    PubMed

    Hoermann, Astrid; Cicin-Sain, Damjan; Jaeger, Johannes

    2016-03-15

    Understanding eukaryotic transcriptional regulation and its role in development and pattern formation is one of the big challenges in biology today. Most attempts at tackling this problem either focus on the molecular details of transcription factor binding, or aim at genome-wide prediction of expression patterns from sequence through bioinformatics and mathematical modelling. Here we bridge the gap between these two complementary approaches by providing an integrative model of cis-regulatory elements governing the expression of the gap gene giant (gt) in the blastoderm embryo of Drosophila melanogaster. We use a reverse-engineering method, where mathematical models are fit to quantitative spatio-temporal reporter gene expression data to infer the regulatory mechanisms underlying gt expression in its anterior and posterior domains. These models are validated through prediction of gene expression in mutant backgrounds. A detailed analysis of our data and models reveals that gt is regulated by domain-specific CREs at early stages, while a late element drives expression in both the anterior and the posterior domains. Initial gt expression depends exclusively on inputs from maternal factors. Later, gap gene cross-repression and gt auto-activation become increasingly important. We show that auto-regulation creates a positive feedback, which mediates the transition from early to late stages of regulation. We confirm the existence and role of gt auto-activation through targeted mutagenesis of Gt transcription factor binding sites. In summary, our analysis provides a comprehensive picture of spatio-temporal gene regulation by different interacting enhancer elements for an important developmental regulator. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  17. UVB-induced mutagenesis in hairless {lambda}lacZ-transgenic mice

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

    Frijhoff, A.F.W.; Rebel, H.; Mientjes, E.J.

    UVB-induced mutagenesis was studied in hairless 40.6 transgenic mice (Muta{trademark}Mouse), which contain the {lambda}gt1OlacZ shuttle vector as a target for mutagenesis. Mice were exposed at the dorsal side to either single doses of 200, 500, 800, or 1000 J/m{sup 2} UVB or to two successive irradiations of either 200 and 800 J/m{sup 2} UVB, with intervals of 1,3, or 5 days, or to 800 and 200 J/m{sup 2} UVB with a 5-day interval. At 23 days after the last exposure, lacZ mutant frequencies (MF) were determined in the epidermis. The lacZ MF increased linearly with increasing dose of UVB. Themore » mutagenic effect of two successive irradiations appeared to be additive. The UV-induced mutation spectrum was dominated by G:C{r_arrow}A:T transitions at dipyrimidine sites. DNA-sequence analysis of spontaneously mutated phages showed a diverse spectrum consisting of insertions, deletions and G:C {r_arrow} A:T transitions at CpG sites. the results indicate that the hairless {lambda}lacZ-transgenic mouse is a suitable in vivo model for studying UVB-induced mutations. 29 refs., 5 tabs.« less

  18. Role of the BK channel (KCa1.1) during activation of electrogenic K+ secretion in guinea pig distal colon

    PubMed Central

    Zhang, Jin; Halm, Susan T.

    2012-01-01

    Secretagogues acting at a variety of receptor types activate electrogenic K+ secretion in guinea pig distal colon, often accompanied by Cl− secretion. Distinct blockers of KCa1.1 (BK, Kcnma1), iberiotoxin (IbTx), and paxilline inhibited the negative short-circuit current (Isc) associated with K+ secretion. Mucosal addition of IbTx inhibited epinephrine-activated Isc (epiIsc) and transepithelial conductance (epiGt) consistent with K+ secretion occurring via apical membrane KCa1.1. The concentration dependence of IbTx inhibition of epiIsc yielded an IC50 of 193 nM, with a maximal inhibition of 51%. Similarly, IbTx inhibited epiGt with an IC50 of 220 nM and maximal inhibition of 48%. Mucosally added paxilline (10 μM) inhibited epiIsc and epiGt by ∼50%. IbTx and paxilline also inhibited Isc activated by mucosal ATP, supporting apical KCa1.1 as a requirement for this K+ secretagogue. Responses to IbTx and paxilline indicated that a component of K+ secretion occurred during activation of Cl− secretion by prostaglandin-E2 and cholinergic stimulation. Analysis of KCa1.1α mRNA expression in distal colonic epithelial cells indicated the presence of the ZERO splice variant and three splice variants for the COOH terminus. The presence of the regulatory β-subunits KCaβ1 and KCaβ4 also was demonstrated. Immunolocalization supported the presence of KCa1.1α in apical and basolateral membranes of surface and crypt cells. Together these results support a cellular mechanism for electrogenic K+ secretion involving apical membrane KCa1.1 during activation by several secretagogue types, but the observed K+ secretion likely required the activity of additional K+ channel types in the apical membrane. PMID:23064759

  19. Cloning and tissue distribution of rat hear fatty acid binding protein mRNA: identical forms in heart and skeletal muscle

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

    Claffey, K.P.; Herrera, V.L.; Brecher, P.

    1987-12-01

    A fatty acid binding protein (FABP) as been identified and characterized in rat heart, but the function and regulation of this protein are unclear. In this study the cDNA for rat heart FABP was cloned from a lambda gt11 library. Sequencing of the cDNA showed an open reading frame coding for a protein with 133 amino acids and a calculated size of 14,776 daltons. Several differences were found between the sequence determined from the cDNA and that reported previously by protein sequencing techniques. Northern blot analysis using rat heart FABP cDNA as a probe established the presence of an abundantmore » mRNA in rat heart about 0.85 kilobases in length. This mRNA was detected, but was not abundant, in fetal heart tissue. Tissue distribution studies showed a similar mRNA species in red, but not white, skeletal muscle. In general, the mRNA tissue distribution was similar to that of the protein detected by Western immunoblot analysis, suggesting that heart FABP expression may be regulated at the transcriptional level. S1 nuclease mapping studies confirmed that the mRNA hybridized to rat heart FABP cDNA was identical in heart and red skeletal muscle throughout the entire open reading frame. The structural differences between heart FABP and other members of this multigene family may be related to the functional requirements of oxidative muscle for fatty acids as a fuel source.« less

  20. The characterisation of hepatic mitochondrial function in patients with non-alcoholic fatty liver disease (NAFLD) using the 13C-ketoisocaproate breath test.

    PubMed

    Afolabi, Paul R; Scorletti, Eleonora; Smith, Debbie E; Almehmadi, Amal A; Calder, Philip C; Byrne, Christopher D

    2018-06-26

    Hepatic mitochondrial function (HMF) assessed by the <sup>13</sup>C-ketoisocaproate breath test (<sup>13</sup>C-KICA BT) has been previously shown to be significantly associated with the severity of biopsy proven non-alcoholic fatty liver disease (NAFLD). However, it is uncertain whether any perturbation in HMF relates specifically to severity of liver disease or factors associated with metabolic syndrome within non-alcoholic fatty liver disease (NAFLD). Our aim was to investigate whether there was any change in HMF assessed by <sup>13</sup>C-KICA BT in patients with NAFLD compared to control subjects, and to assess the factors that are independently associated with HMF. 77 patients with NAFLD and 11 healthy control subjects were studied. HMF was assessed using <sup>13</sup>C-KICA BT and expressed as cumulative % <sup>13</sup>C-dose recovered on breath over 1hr (cPDR over 1hr). Liver fat and fibrosis was assessed by transient elastography. Multi-variable linear regression modelling was undertaken to test the independence of associations with HMF. HMF (cPDR over 1hr) was lower in NAFLD compared to controls [13.4% (4.8) v. 21.0% (6.3); p< 0.0001)]. In NAFLD, HMF was lower in patients with diabetes versus no diabetes [12.7% (3.4) v. 14.3% (6.1); p=0.003)]. Regression modelling showed age (β= -0.08; p=0.01), waist circumference (β= -0.08; p=0.01), hip circumference (β= -0.04; p=0.01), aspartate aminotransferase (AST) (β= -0.05; p=0.01) and diabetes status (β= -1.81; p=0.01) were independently associated with HMF (R<sup>2</sup>= 41.5%; p<0.0001). In patients with NAFLD (compared to healthy subjects), there was a reduction in HMF assessed by the <sup>13</sup>C-KICA BT. Furthermore, in patients with NAFLD, HMF is independent and inversely associated with age, waist and hip circumference, AST and diabetes status. © 2018 IOP Publishing Ltd.

  1. Molecular Cloning and Ethylene Induction of mRNA Encoding a Phytoalexin Elicitor-Releasing Factor, beta-1,3-Endoglucanase, in Soybean.

    PubMed

    Takeuchi, Y; Yoshikawa, M; Takeba, G; Tanaka, K; Shibata, D; Horino, O

    1990-06-01

    Soybean (Glycine max) beta-1,3-endoglucanase (EC 3.2. 1.39) is involved in one of the earliest plant-pathogen interactions that may lead to active disease resistance by releasing elicitor-active carbohydrates from the cell walls of fungal pathogens. Ethylene induced beta-1,3-endoglucanase activity to 2- to 3-fold higher levels in cotyledons of soybean seedlings. A specific polyclonal antiserum raised against purified soybean beta-1,3-endoglucanase was used to immunoprecipitate in vitro translation products, demonstrating that ethylene induction increased translatable beta-1,3-endoglucanase mRNA. Several cDNA clones for the endoglucanase gene were obtained by antibody screening of a lambda-gt11 expression library prepared from soybean cotyledons. Hybrid-select translation experiments indicated that the cloned cDNA encoded a 36-kilodalton precursor protein product that was specifically immunoprecipitated with beta-1,3-endoglucanase antiserum. Escherichia coli cells expressing the cloned cDNA also synthesized an immunologically positive protein. Nucleotide sequence of three independent clones revealed a single uninterrupted open reading frame of 1041 nucleotides, corresponding to a polypeptide of 347 residue long. The primary amino acid sequence of beta-1,3-endoglucanase as deduced from the nucleotide sequence was confirmed by direct amino acid sequencing of trypsin digests of the glucanase. The soybean beta-1,3-endoglucanase exhibited 53% amino acid homology to a beta-1,3-glucanase cloned from cultured tobacco cells and 48% homology to a beta-(1,3-1,4)-glucanase from barley. Utilizing the largest cloned cDNA (pEG488) as a hybridization probe, it was found that the increase in translatable beta-1,3-endoglucanase mRNA seen upon ethylene treatment of soybean seedlings was due to 50- to 100-fold increase in steady state mRNA levels, indicating that ethylene regulates gene expression of this enzyme important in disease resistance at the level of gene transcription.

  2. Real-World Study on Sofosbuvir-based Therapies in Asian Americans With Chronic Hepatitis C.

    PubMed

    Pan, Calvin Q; Tiongson, Benjamin C; Hu, Ke-Qin; Han, Steven-Huy B; Tong, Myron; Chu, Danny; Park, James; Lee, Tai Ping; Bhamidimarri, Kalyan Ram; Ma, Xiaoli; Xiao, Pei Ying; Mohanty, Smruti R; Wang, Dan

    2018-06-16

    Limited data exist with regard to treatment outcomes in Asian Americans with chronic hepatitis C (CHC). We evaluated sofosbuvir (SOF)-based regimens in a national cohort of Asian Americans. Eligible Asian Americans patients with CHC who had posttreatment follow-up of 24 weeks for SOF -based therapies from December 2013 to June 2017 were enrolled from 11 sites across the United States. The primary endpoint was sustained virologic response (SVR) rates at posttreatment weeks 12 and 24. Secondary endpoints were to evaluate safety by tolerability and adverse events (AEs). Among 231 patients screened, 186 were enrolled. At baseline, 31% (57/186) patients were cirrhotic, 34% (63/186) were treatment experienced. Most of the subjects (42%, 79/186) received ledispavir/SOF therapy. The overall SVR12 was 95%, ranging from 86% in genotype (GT) 1b on SOF+ribavirin to 100% in GT 1b patients on ledipasvir/SOF at subgroup analyses. SVR12 was significantly lower in cirrhotic than in noncirrhotic patients [88% (50/57) vs. 98% (126/129), P<0.01]. Stratified by GT, SVR12 were: 96% (43/45) in GT 1a; 93% (67/72) in GT 1b; 100% (23/23) in GT 2; 90% (19/21) in GT 3; 100% (1/1) in GT 4; 83% (5/6) in GT 5; and 100% (16/16) in GT 6. Cirrhotic patients with treatment failure were primarily GT 1, (GT 1a, n=2; GT 1b, n=4) with 1 GT 5 (n=1). Patients tolerated the treatment without serious AEs. Late relapse occurred in 1 patient after achieving SVR12. In Asian Americans with CHC, SOF-based regimens were well tolerated without serious AEs and could achieve high SVR12 regardless of hepatitis C viral infection GT.

  3. Effect of atmospheric extinction on laser rangefinder performance at 1.54 and 0.6 microns

    NASA Technical Reports Server (NTRS)

    Hutt, D. L.; Theriault, J.-M.; Larochelle, V.; Bonnier, D.

    1992-01-01

    Extinction of laser rangefinder (LRF) pulses by the atmosphere depends on the wavelength, weather conditions, and aerosol concentration along the optical path. In the IR, extinction is due to absorption by molecular constituents and scattering and absorption by aerosols. The total atmospheric extinction alpha(lambda) is the sum of the molecular and aerosol contributions, alpha(sub m)(lambda)and Alpha(sub a)(lambda). We present simple expressions for alpha(sub m)(lambda) and alpha(sub a)(lambda) for two LRF sources: Er:glass and CO2 which operate at 1.54 and 10.6 microns, respectively. The expressions are based on accepted models of atmospheric aerosols and molecular extinction and give an estimate of alpha(lambda) as a function of standard meteorological parameters, assuming horizontal beam propagation. Signal-to-noise ratios of LRF returns, measured from a reference target under different weather conditions are compared to predictions based on the estimate of alpha(lambda).

  4. Spectroscopy of the neutron-rich hypernucleus He Λ 7 from electron scattering

    DOE PAGES

    Gogami, T.; Chen, C.; Kawama, D.; ...

    2016-08-12

    Here, the missing mass spectroscopy of themore » $$^{7}_{\\Lambda}$$He hypernucleus was performed, using the $$^{7}$$Li$$(e,e^{\\prime}K^{+})^{7}_{\\Lambda}$$He reaction at the Thomas Jefferson National Accelerator Facility Hall C. The $$\\Lambda$$ binding energy of the ground state (1/2$$^{+}$$) was determined with a smaller error than that of the previous measurement, being $$B_{\\Lambda}$$ = 5.55 $$\\pm$$ 0.10(stat.) $$\\pm$$ 0.11(sys.) MeV. The experiment also provided new insight into charge symmetry breaking in p-shell hypernuclear systems. Finally, a peak at $$B_{\\Lambda}$$ = 3.65 $$\\pm$$ 0.20(stat.) $$\\pm$$ 0.11(sys.) MeV was observed and assigned as a mixture of 3/2$$^{+}$$ and 5/2$$^{+}$$ states, confirming the "gluelike" behavior of $$\\Lambda$$, which makes an unstable state in $$^{6}$$He stable against neutron emission.« less

  5. Prolyl Endopeptidase (PREP) is Associated With Male Reproductive Functions and Gamete Physiology in Mice.

    PubMed

    Dotolo, Raffaele; Kim, Jung Dae; Pariante, Paolo; Minucci, Sergio; Diano, Sabrina

    2016-03-01

    Prolyl endopeptidase (PREP) is a serine protease which has been implicated in many biological processes, such as the maturation and degradation of peptide hormones and neuropeptides, learning and memory, cell proliferation and differentiation, and glucose metabolism. A small number of reports have also suggested PREP participation in both male and female reproduction-associated processes. In the present work, we examined PREP distribution in male germ cells and studied the effects of its knockdown (Prep(gt/gt)) on testis and sperm in adult mice. The protein is expressed and localized in elongating spermatids and luminal spermatozoa of wild type (wt) mice, as well as Sertoli, Leydig, and peritubular cells. PREP is also expressed in the head and midpiece of epididymal spermatozoa, whereas the remaining tail region shows a weaker signal. Furthermore, testis weight, histology of seminiferous tubules, and epididymal sperm parameters were assessed in wt and Prep(gt/gt) mice: wild type testes have larger average tubule and lumen diameter; in addition, lumenal composition of seminiferous tubules is dissimilar between wt and Prep(gt/gt), as the percentage of spermiated tubules is much higher in wt. Finally, total sperm count, sperm motility, and normal morphology are also higher in wt than in Prep(gt/gt). These results show for the first time that the expression of PREP could be necessary for a correct reproductive function, and suggest that the enzyme may play a role in mouse spermatogenesis and sperm physiology. © 2015 Wiley Periodicals, Inc.

  6. Mass Balance of the West Antarctic Ice-Sheet from ICESat Measurements

    NASA Technical Reports Server (NTRS)

    Zwally, H. Jay; Li, Jun; Robins, John; Saba, Jack L.; Yi, Donghui

    2011-01-01

    Mass balance estimates for 2003-2008 are derived from ICESat laser altimetry and compared with estimates for 1992-2002 derived from ERS radar altimetry. The net mass balance of 3 drainage systems (Pine Island, Thwaites/Smith, and the coast of Marie Bryd) for 2003-2008 is a loss of 100 Gt/yr, which increased from a loss of 70 Gt/yr for the earlier period. The DS including the Bindschadler and MacAyeal ice streams draining into the Ross Ice Shelf has a mass gain of 11 Gt/yr for 2003-2008, compared to an earlier loss of 70 Gt/yr. The DS including the Whillans and Kamb ice streams has a mass gain of 12 Gt/yr, including a significant thickening on the upper part of the Kamb DS, compared to a earlier gain of 6 Gt/yr (includes interpolation for a large portion of the DS). The other two DS discharging into the Ronne Ice Shelf and the northern Ellsworth Coast have a mass gain of 39 Gt/yr, compared to a gain of 4 Gt/yr for the earlier period. Overall, the increased losses of 30 Gt/yr in the Pine Island, Thwaites/Smith, and the coast of Marie Bryd DSs are exceeded by increased gains of 59 Gt/yr in the other 4 DS. Overall, the mass loss from the West Antarctic ice sheet has decreased to 38 Gt/yr from the earlier loss of 67 Gt/yr, reducing the contribution to sea level rise to 0.11 mm/yr from 0.19 mm/yr

  7. The risk of renal disease is increased in lambda myeloma with bone marrow amyloid deposits.

    PubMed

    Kozlowski, Piotr; Montgomery, Scott; Befekadu, Rahel; Hahn-Strömberg, Victoria

    2017-01-01

    Light chain amyloidosis (AL) is a rare deposition disease and is present in 10-15% of patients with myeloma (MM). In contrast to symptomatic AL in MM, presence of bone marrow (BM) amyloid deposits (AD) in MM is not connected to kidney damage. Renal AD but not BM-AD occur mostly in MM with lambda paraprotein (lambda MM). We investigated amyloid presence in BM clots taken at diagnosis in 84 patients with symptomatic MM and compared disease characteristics in MM with kappa paraprotein (kappa MM)/lambda MM with and without BM-AD. Lambda MM with BM-AD was compared with kappa MM without BM-AD, kappa MM with BM-AD, and lambda MM without BM-AD: lambda MM with BM-AD patients had a significantly higher mean creatinine level (4.23 mg/dL vs 1.69, 1.14, and 1.28 mg/dL, respectively) and a higher proportion presented with severe kidney failure (6/11 [55%] vs 6/32 [19%], 1/22 [5%], and 3/19 [16%], respectively). Proteinuria was more common in lambda MM with BM-AD patients compared with kappa MM without BM-AD patients (8/11 [73%] vs 5/32 [16%], respectively). Kidney damage was more common in lambda MM with BM-AD indicating presence of renal AD.

  8. Expression of a Dianthus flavonoid glucosyltransferase in Saccharomyces cerevisiae for whole-cell biocatalysis.

    PubMed

    Werner, Sean R; Morgan, John A

    2009-07-15

    Glycosyltransferases are promising biocatalysts for the synthesis of small molecule glycosides. In this study, Saccharomyces cerevisiae expressing a flavonoid glucosyltransferase (GT) from Dianthus caryophyllus (carnation) was investigated as a whole-cell biocatalyst. Two yeast expression systems were compared using the flavonoid naringenin as a model substrate. Under in vitro conditions, naringenin-7-O-glucoside was formed and a higher specific glucosyl transfer activity was found using a galactose inducible expression system compared to a constitutive expression system. However, S. cerevisiae expressing the GT constitutively was significantly more productive than the galactose inducible system under in vivo conditions. Interestingly, the glycosides were recovered directly from the culture broth and did not accumulate intracellularly. A previously uncharacterized naringenin glycoside formed using the D. caryophyllus GT was identified as naringenin-4'-O-glucoside. It was found that S. cerevisiae cells hydrolyze naringenin-7-O-glucoside during whole-cell biocatalysis, resulting in a low final glycoside titer. When phloretin was added as a substrate to the yeast strain expressing the GT constitutively, the natural product phlorizin was formed. This study demonstrates S. cerevisiae is a promising whole-cell biocatalyst host for the production of valuable glycosides.

  9. The Correlation Between Interferon Lambda 3 Gene Polymorphisms and Susceptibility to Hepatitis B Virus Infection

    PubMed Central

    Heidari, Zahra; Moudi, Bita; Mahmoudzadeh-Sagheb, Hamidreza; Hashemi, Mohammad

    2016-01-01

    Background Cytokines are proteins that mediate innate and adaptive immunity responses. It is hypothesized that interferon lambda 3 (IFNL3) levels can influence the outcome of chronic hepatitis B virus (HBV) infection. Polymorphisms in IFN genes have been associated with response to infection. Objectives This study was carried-out to investigate the association of IFNL3 gene polymorphisms (rs12979860 and rs8099917) with HBV susceptibility, in chronic HBV-infected patients. Patients and Methods In this case-control study, we determined IFNL3 single nucleotide polymorphisms (SNPs) (rs12979860 and rs8099917) in 221 individuals, with chronic HBV infection, and 200 healthy individuals, who were voluntary blood donors, with negative test for HBV. Alleles and genotypes analyses were performed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Results The frequencies of the rs12979860 and rs8099917 genotypes were not significantly different between the HBV-infected and the control groups (CC:CT:TT of 30.3%:48.0%:21.7% vs. 33.0%:49.0%:18.0%, P > 0.05, and GG:GT:TT of 5.8%:39.4%:54.8% vs. 5.0%:41.0%:54.0%, P > 0.05, respectively). Also, the frequencies of the alleles were not significantly different between both groups (C:T of 54.3%:45.7% vs. 57.5%:42.5%, P > 0.05, and G:T of 25.6%:74.4% vs. 25.5%:74.5%, P > 0.05, respectively) and the chronic HBV infection. There were no significant differences between patients, with at least one rs12979860C and or rs8099917T alleles compared to the healthy controls (rs12979860: CT + CC:TT, OR = 1.26, 95%CI = 0.78 - 2.04, P = 0.341 and rs8099917: GT + TT:GG, OR = 1.03, 95%CI = 0.70 - 1.51, P = 0.877, respectively). Conclusions Our study showed no correlation between rs12979860 and rs8099917 SNPs and chronic HBV infection. Further studies, with larger sample sizes and different ethnicities, are necessary to validate our findings. PMID:27226800

  10. A Categorification of the Crystal Isomorphism B 1,1 B + B(Lambda i) = B(Lambdasigma (i) and a Graphical Calculus for the Shifted Symmetric Functions

    NASA Astrophysics Data System (ADS)

    Kvinge, Henry

    We prove two results at the intersection of Lie theory and the representation theory of symmetric groups, Hecke algebras, and their generalizations. The first is a categorification of the crystal isomorphism B. (1,1) tensor B1,1 ⊕ B(Lambdai ) ≅ B(Lambdasigma (i)). Here B(Lambdai and B(Lambda sigma(i)) are two affine type highest weight crystals of weight Lambdai and Lambdasigma (i) respectively, sigma is a specific map from the Dynkin indexing set I to itself, and B1,1 is a Kirillov-Reshetikhin crystal. We show that this crystal isomorphism is in fact the shadow of a richer module-theoretic phenomenon in the representation theory of Khovanov-Lauda-Rouquier algebras of classical affine type. Our second result identifies the center EndH'( 1) of Khovanov's Heisenberg category H', as the algebra of shifted symmetric functions Lambda* of Okounkov and Olshanski, i.e. End H'(1) ≅ Lambda*. This isomorphism provides us with a graphical calculus for Lambda*. It also allows us to describe EndH'(1) in terms of the transition and co-transition measure of Kerov and the noncommutative probability spaces of Biane.

  11. On the variability of LSI+61 deg 303 (identical with GT 0236)

    NASA Technical Reports Server (NTRS)

    Tanzi, E. G.; Bignami, G. F.; Caraveo, P. A.; Maraschi, L.; Sormani, F.; Treves, A.

    1982-01-01

    Out of six long and six short wavelength observations, one spectrum exhibits a significant photometric variation: or approximately 20%. Interpreting the continuum as due to superposition of an early B main sequence star plus a gaseous component contributing at lambda 2000 A, the wavelength dependence of the variation suggests that it derives from the latter component. The data indicate that if the observed variation is phase dependent, a minimum should occur between phases 0.8 and 0.2. However, since the variation is observed in only one spectrum, it may well be erratic.

  12. Genomic organization of the human gene (CA5) and pseudogene for mitochondrial carbonic anhydrase V and their localization to chromosomes 16q and 16p

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

    Nagao, Yoshiro; Sly, W.S.; Batanian, J.R.

    1995-08-10

    Carbonic anhydrase V (CA V) is expressed in mitochondrial matrix in liver and several other tissues. It is of interest for its putative roles in providing bicarbonate to carbamoyl phosphate synthetase for ureagenesis and to pyruvate carboxylase for gluconeogenesis and its possible importance in explaining certain inherited metabolic disorders with hyperammonemia and hypoglycemia. Following the recent characterization of the cDNA for human CA V, we report the isolation of the human gene from two {lambda} genomic libraries and its characterization. The CA V gene (CA5) is approximately 50 kb long and contains 7 exons and 6 introns. The exon-intron boundariesmore » are found in positions identical to those determined for the previously described CA II, CA III, and CA VII genes. Like the CA VII gene, CA5 does not contain typical TATA and CAAT promoter elements in the 5{prime} flanking region but does contain a TTTAA sequence 147 nucleotides upstream of the initiation codon. CA5 also contains a 12-bp GT-rich segment beginning 13 bp downstream of the polyadenylation signal in the 3{prime} untranslated region of exon 7. FISH analysis allowed CA5 to be assigned to chromosome 16q24.3. An unprocessed pseudogene containing sequence homologous to exons 3-7 and introns 3-6 was also isolated and was assigned by FISH analysis to chromosome 16p11.2-p12. 22 refs., 4 figs., 1 tab.« less

  13. Patterns of accelerometer-derived sedentary time across the lifespan.

    PubMed

    Santos, Diana A; Júdice, Pedro B; Magalhães, João P; Correia, Inês R; Silva, Analiza M; Baptista, Fátima; Sardinha, Luís B

    2018-05-10

    We aimed to describe ST and its patterns on a national level. A hip-worn accelerometer (ActiGraph GT1M) was used to collect data during waking hours from 4575 Portuguese' participants from 2007-2009 (2683 females) aged 10-102 years old. Data was presented by sex, in 5-years age intervals, and by adolescents (n=2833), adults (n=1122), and older adults (n=620). Lambda-mu-sigma (LMS) smoothed percentile curves were estimated. Girls, women, and older women spent 61, 57, and 64% of wear time in ST, respectively. In males, ST represented 57, 60, and 62% of wear time respectively for boys, men, and older men. Comparing to other age groups, older adults spent a larger amount of ST in bouts ≥30-min (women: 33%, men: 39% of total ST). The number of breaks/ST hour were: 10.6 in girls, 11.7 in women, and 9.6 in older women. In males, the number of breaks/ST hour were: 11.2, 10.5, and 8.5 for boys, men, and older men. In conclusion, ST was not consistently higher at older ages. Instead, we found that the potential critical moments in which ST may be higher are during adolescence and in the transition from adulthood into older adulthood, which represents critical periods for interventions.

  14. cDNA cloning and characterization of UDP-glucose: anthocyanidin 3-O-glucosyltransferase in Freesia hybrida.

    PubMed

    Sui, Xin; Gao, Xiang; Ao, Man; Wang, Qinmei; Yang, Dan; Wang, Meng; Fu, Yang; Wang, Li

    2011-07-01

    The enzyme that catalyzes the formation of the first stable anthocyanin in the biosynthesis of natural compounds is UDP-glucose: anthocyanidin 3-O-glucosyltransferase (UF3GT). A cDNA clone (Fh3GT1) encoding UF3GT was isolated from Freesia hybrida. Phylogenetic tree analysis indicated that Fh3GT1 was a novel member of glycosyltransferase, which was classified into monocot subgroups. Semi-quantitative RT-PCR analysis detected transcripts of Fh3GT1 in different organs of F. hybrida and in petals of Freesia cultivars of different colors, and the expression level reached the maximum at the fully opened stage of petals. Characterization of the enzymatic assays indicated that Fh3GT1 had a role in anthocyanin glycoside biosyntheses in vitro. To elucidate the function of Fh3GT1, RNA interference vector (pART-Fh3GT1i) was constructed, and introduced into Petunia grandiflora by Agrobacterium-mediated transformation. Integration of the Fh3GT1 in petunia genome was confirmed by PCR and Southern blotting. SqRT-PCR revealed that the endogenous Ph3GT1 mRNA expression levels decreased in transgenic lines compared with the wild-type. The content of total anthocyanin pigments also decreased with the reduction of mRNA transcript levels, and the transgenic petunia plants had significant changes on their flower colors. In summary, this work identified a UF3GT gene from Freesia hybrida and demonstrated a method to modify plant flower color by redirecting the anthocyanin biosynthesis.

  15. The modelled surface mass balance of the Antarctic Peninsula at 5.5 km horizontal resolution

    NASA Astrophysics Data System (ADS)

    van Wessem, J. M.; Ligtenberg, S. R. M.; Reijmer, C. H.; van de Berg, W. J.; van den Broeke, M. R.; Barrand, N. E.; Thomas, E. R.; Turner, J.; Wuite, J.; Scambos, T. A.; van Meijgaard, E.

    2016-02-01

    This study presents a high-resolution (˜ 5.5 km) estimate of surface mass balance (SMB) over the period 1979-2014 for the Antarctic Peninsula (AP), generated by the regional atmospheric climate model RACMO2.3 and a firn densification model (FDM). RACMO2.3 is used to force the FDM, which calculates processes in the snowpack, such as meltwater percolation, refreezing and runoff. We evaluate model output with 132 in situ SMB observations and discharge rates from six glacier drainage basins, and find that the model realistically simulates the strong spatial variability in precipitation, but that significant biases remain as a result of the highly complex topography of the AP. It is also clear that the observations significantly underrepresent the high-accumulation regimes, complicating a full model evaluation. The SMB map reveals large accumulation gradients, with precipitation values above 3000 mm we yr-1 in the western AP (WAP) and below 500 mm we yr-1 in the eastern AP (EAP), not resolved by coarser data sets such as ERA-Interim. The average AP ice-sheet-integrated SMB, including ice shelves (an area of 4.1 × 105 km2), is estimated at 351 Gt yr-1 with an interannual variability of 58 Gt yr-1, which is dominated by precipitation (PR) (365 ± 57 Gt yr-1). The WAP (2.4 × 105 km2) SMB (276 ± 47 Gt yr-1), where PR is large (276 ± 47 Gt yr-1), dominates over the EAP (1.7 × 105 km2) SMB (75 ± 11 Gt yr-1) and PR (84 ± 11 Gt yr-1). Total sublimation is 11 ± 2 Gt yr-1 and meltwater runoff into the ocean is 4 ± 4 Gt yr-1. There are no significant trends in any of the modelled AP SMB components, except for snowmelt that shows a significant decrease over the last 36 years (-0.36 Gt yr-2).

  16. Construction of heat-inducible expression vector of Corynebacterium glutamicum and C. ammoniagenes: fusion of lambda operator with promoters isolated from C. ammoniagenes.

    PubMed

    Park, Jong-Uk; Jo, Jae-Hyung; Kim, Young-Ji; Chung, So-Sun; Lee, Jin-Ho; Lee, Hyune Hwan

    2008-04-01

    The heat-inducible expression vectors for Corynebacterium glutamicum and C. ammoniagenes were constructed by using the lambdaOL1 and the cryptic promoters, CJ1 and CJ4 that express genes constitutively in C. ammoniagenes.. Although the promoters were isolated from C. ammoniagenes, CJ1 and CJ4 were also active in C. glutamicum. To construct vectors, the OL1 from the lambdaPL promoter was isolated and fused to the CJ1 and CJ4 promoters by recombinant PCR. The resulting artificial promoters, CJ1O and CJ4O, which have one lambdaOL1, and CJ1OX2, which has two successive lambdaOL1, were fused to the green fluorescent protein (GFP) gene followed by subcloning into pCES208. The expression of GFP in the corynebacteria harboring the vectors was regulated successfully by the temperature sensitive cI857 repressor. Among them, C. ammoniagenes harboring plasmid pCJ1OX2G containing GFP fused to CJ1OX2 showed more GFP than the other ones and the expression was tightly regulated by the repressor. To construct the generally applicable expression vector using the plasmid pCJ1OX2G, the His-tag, enterokinase (EK) moiety, and the MCS were inserted in front of the GFP gene. Using the vector, the expression of pyrR from C. glutamicum was tried by temperature shift-up. The results indicated that the constructed vectors (pCeHEMG) can be successfully used in the expression and regulation of foreign genes in corynebacteria.

  17. A UDP-Glucose:Monoterpenol Glucosyltransferase Adds to the Chemical Diversity of the Grapevine Metabolome1[W

    PubMed Central

    Bönisch, Friedericke; Frotscher, Johanna; Stanitzek, Sarah; Rühl, Ernst; Wüst, Matthias; Bitz, Oliver; Schwab, Wilfried

    2014-01-01

    Terpenoids represent one of the major classes of natural products and serve different biological functions. In grape (Vitis vinifera), a large fraction of these compounds is present as nonvolatile terpene glycosides. We have extracted putative glycosyltransferase (GT) sequences from the grape genome database that show similarity to Arabidopsis (Arabidopsis thaliana) GTs whose encoded proteins glucosylate a diversity of terpenes. Spatial and temporal expression levels of the potential VvGT genes were determined in five different grapevine varieties. Heterologous expression and biochemical assays of candidate genes led to the identification of a UDP-glucose:monoterpenol β-d-glucosyltransferase (VvGT7). The VvGT7 gene was expressed in various tissues in accordance with monoterpenyl glucoside accumulation in grape cultivars. Twelve allelic VvGT7 genes were isolated from five cultivars, and their encoded proteins were biochemically analyzed. They varied in substrate preference and catalytic activity. Three amino acids, which corresponded to none of the determinants previously identified for other plant GTs, were found to be important for enzymatic catalysis. Site-specific mutagenesis along with the analysis of allelic proteins also revealed amino acids that impact catalytic activity and substrate tolerance. These results demonstrate that VvGT7 may contribute to the production of geranyl and neryl glucoside during grape ripening. PMID:24784757

  18. Elevated expression of esterase and cytochrome P450 are related with lambda-cyhalothrin resistance and lead to cross resistance in Aphis glycines Matsumura.

    PubMed

    Xi, Jinghui; Pan, Yiou; Bi, Rui; Gao, Xiwu; Chen, Xuewei; Peng, Tianfei; Zhang, Min; Zhang, Hua; Hu, Xiaoyue; Shang, Qingli

    2015-02-01

    A resistant strain of the Aphis glycines Matsumura (CRR) has developed 76.67-fold resistance to lambda-cyhalothrin compared with the susceptible (CSS) strain. Synergists piperonyl butoxide (PBO), S,S,S-Tributyltrithiophosphate (DEF) and triphenyl phosphate (TPP) dramatically increased the toxicity of lambda-cyhalothrin to the resistant strain. Bioassay results indicated that the CRR strain had developed high levels of cross-resistance to chlorpyrifos (11.66-fold), acephate (8.20-fold), cypermethrin (53.24-fold), esfenvalerate (13.83-fold), cyfluthrin (9.64-fold), carbofuran (14.60-fold), methomyl (9.32-fold) and bifenthrin (4.81-fold), but did not have cross-resistance to chlorfenapyr, imidacloprid, diafenthiuron, abamectin. The transcriptional levels of CYP6A2-like, CYP6A14-like and cytochrome b-c1 complex subunit 9-like increased significantly in the resistant strain than that in the susceptible. Similar trend were observed in the transcripts and DNA copy number of CarE and E4 esterase. Overall, these results demonstrate that increased esterase hydrolysis activity, combined with elevated cytochrome P450 monooxygenase detoxicatication, plays an important role in the high levels of lambda-cyhalothrin resistance and can cause cross-resistance to other insecticides in the CRR strain. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Large subunit of the ribonucleotide reductase gene is a virulent factor and plays a critical role in Marek's disease virus pathogenesis

    USDA-ARS?s Scientific Manuscript database

    Marek’s disease virus (MDV) encodes a ribonucleotide reductase (RR) gene consisting of two subunits UL39 (RR1) and UL40 (RR2). Both RR1 and RR2 form an active holoenzyme and are necessary for enzyme activity. This gene was indentified by monoclonal antibody T81 in a gt11 MDV expression library and f...

  20. Implementation of Universal Microsatellite Instability and Immunohistochemistry Screening for Diagnosing Lynch Syndrome in a Large Academic Medical Center

    PubMed Central

    Heald, Brandie; Plesec, Thomas; Liu, Xiuli; Pai, Rish; Patil, Deepa; Moline, Jessica; Sharp, Richard R.; Burke, Carol A.; Kalady, Matthew F.; Church, James; Eng, Charis

    2013-01-01

    Purpose In 2009, the Evaluation of Genomic Applications in Practice and Prevention recommended that all colorectal cancers (CRCs) be screened for Lynch syndrome (LS) through microsatellite instability (MSI) or immunohistochemistry (IHC). No studies report how this process is implemented on a health system–wide basis. Methods Since 2004, Cleveland Clinic has screened CRC specimens with MSI/IHC. Between January 2004 and July 2007, MSI/IHC results went only to the colorectal surgeon (approach 1). Between August 2007 and June 2008, colorectal surgeons and a genetic counselor received the MSI/IHC results, and the counselor e-mailed the colorectal surgeon regarding appropriate patients for genetic counseling (GC) referral (approach 2). After July 2008, the colorectal surgeon and counselor received MSI/IHC results, but the counselor contacted the patient to facilitate referral (approach 3). In approaches 2 and 3, patients were presumed to have sporadic CRC if the tumor lacked MLH1 expression and was also BRAF mutated or if the patient was diagnosed at age greater than 72 years and had no cancer family history. Results Abnormal MSI/IHC results occurred in 178 (16%) of 1,108 patients. In approach 1, 21 (55%) of 38 patients with abnormal MSI/IHC were referred for GC, 12 (32%) of 38 underwent GC, and 10 (26%) of 38 underwent genetic testing (GT). In approach 2, nine (82%) of 11 patients were referred for GC, seven (64%) of 11 underwent GC, and five (45%) of 11 underwent GT. In approach 3, 56 (100%) of 56 patients were referred for GC, 40 (71%) of 56 underwent GC, and 37 (66%) of 56 underwent GT. Time from referral to GC was 10-fold quicker in approach 3 than approach 1. Conclusion Implementation of universal MSI/IHC with GC/GT, along with effective multidisciplinary communication and plans of responsibility for patient contact, resulted in increased identification of patients with LS. PMID:23401454

  1. Expression of feeding-related peptide receptors mRNA in GT1-7 cell line and roles of leptin and orexins in control of GnRH secretion.

    PubMed

    Yang, Ying; Zhou, Li-bin; Liu, Shang-quan; Tang, Jing-feng; Li, Feng-yin; Li, Rong-ying; Song, Huai-dong; Chen, Ming-dao

    2005-08-01

    To investigate the expression of feeding-related peptide receptors mRNA in GT1-7 cell line and roles of leptin and orexins in the control of GnRH secretion. Receptors of bombesin3, cholecystokinin (CCK)-A, CCK-B, glucagon-like peptide (GLP)1, melanin-concentrating hormone (MCH)1, orexin1, orexin2, neuromedin-B, neuropeptide Y (NPY)1 and NPY5, neurotensin (NT)1, NT2, NT3, and leptin receptor long form mRNA in GT1-7 cells were detected by reversed transcriptase-polymerase chain reaction. GT1-7 cells were treated with leptin, orexin A and orexin B at a cohort of concentrations for different lengths of time, and GnRH in medium was determined by radioimmunoassay (RIA). Receptors of bombesin 3, CCK-B, GLP1, MCH1, orexin1, neuromedin-B, NPY1, NPY5, NT1, NT3, and leptin receptor long form mRNA were expressed in GT1-7 cells, of which, receptors of GLP1, neuromedin-B, NPY1, and NT3 were highly expressed. No amplified fragments of orexin2, NT2, and CCK-A receptor cDNA were generated with GT1-7 RNA, indicating that the GT1-7 cells did not express mRNA of them. Leptin induced a significant stimulation of GnRH release, the results being most significant at 0.1 nmol/L for 15 min. In contrast to other studies in hypothalamic explants, neither orexin A nor orexin B affected basal GnRH secretion over a wide range of concentrations ranging from 1 nmol/L to 500 nmol/Lat 15, 30, and 60 min. Feeding and reproductive function are closely linked. Many orexigenic and anorexigenic signals may control feeding behavior as well as alter GnRH secretion through their receptors on GnRH neurons.

  2. Measurement of sigma Lambda b0/sigma B0 x B(Lambda b0-->Lambda c+pi-)/B(B0-->D+pi-) in pp collisions at square root s=1.96 TeV.

    PubMed

    Abulencia, A; Adelman, J; Affolder, T; Akimoto, T; Albrow, M G; Ambrose, D; Amerio, S; Amidei, D; Anastassov, A; Anikeev, K; Annovi, A; Antos, J; Aoki, M; Apollinari, G; Arguin, J-F; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Azfar, F; Azzi-Bacchetta, P; Azzurri, P; Bacchetta, N; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Baroiant, S; Bartsch, V; Bauer, G; Bedeschi, F; Behari, S; Belforte, S; Bellettini, G; Bellinger, J; Belloni, A; Benjamin, D; Beretvas, A; Beringer, J; Berry, T; Bhatti, A; Binkley, M; Bisello, D; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bolshov, A; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Budroni, S; Burkett, K; Busetto, G; Bussey, P; Byrum, K L; Cabrera, S; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carillo, S; Carlsmith, D; Carosi, R; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, I; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Ciljak, M; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Coca, M; Compostella, G; Convery, M E; Conway, J; Cooper, B; Copic, K; Cordelli, M; Cortiana, G; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; Cyr, D; DaRonco, S; D'Auria, S; Davies, T; D'Onofrio, M; Dagenhart, D; de Barbaro, P; De Cecco, S; Deisher, A; De Lentdecker, G; Dell'Orso, M; Delli Paoli, F; Demortier, L; Deng, J; Deninno, M; De Pedis, D; Derwent, P F; Di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; DiTuro, P; Dörr, C; Donati, S; Donega, M; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, I; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Field, R; Flanagan, G; Foland, A; Forrester, S; Foster, G W; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garcia, J E; Garberson, F; Garfinkel, A F; Gay, C; Gerberich, H; Gerdes, D; Giagu, S; Giannetti, P; Gibson, A; Gibson, K; Gimmell, J L; Ginsburg, C; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Goldstein, J; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Griffiths, M; Grinstein, S; Grosso-Pilcher, C; Group, R C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Hamilton, A; Han, B-Y; Han, J Y; Handler, R; Happacher, F; Hara, K; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hauser, J; Heijboer, A; Heinemann, B; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Holloway, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ishizawa, Y; Ivanov, A; Iyutin, B; James, E; Jang, D; Jayatilaka, B; Jeans, D; Jensen, H; Jeon, E J; Jindariani, S; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Karchin, P E; Kato, Y; Kemp, Y; Kephart, R; Kerzel, U; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Klute, M; Knuteson, B; Ko, B R; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kovalev, A; Kraan, A C; Kraus, J; Kravchenko, I; Kreps, M; Kroll, J; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhlmann, S E; Kuhr, T; Kusakabe, Y; Kwang, S; Laasanen, A T; Lai, S; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; Le, Y; LeCompte, T; Lee, J; Lee, J; Lee, Y J; Lee, S W; Lefèvre, R; Leonardo, N; Leone, S; Levy, S; Lewis, J D; Lin, C; Lin, C S; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Loverre, P; Lu, R-S; Lucchesi, D; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Lytken, E; Mack, P; MacQueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Manca, G; Margaroli, F; Marginean, R; Marino, C; Marino, C P; Martin, A; Martin, M; Martin, V; Martínez, M; Maruyama, T; Mastrandrea, P; Masubuchi, T; Matsunaga, H; Mattson, M E; Mazini, R; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzemer, S; Menzione, A; Merkel, P; Mesropian, C; Messina, A; Miao, T; Miladinovic, N; Miles, J; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyamoto, A; Moed, S; Moggi, N; Mohr, B; Moore, R; Morello, M; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Nachtman, J; Nagano, A; Naganoma, J; Nakano, I; Napier, A; Necula, V; Neu, C; Neubauer, M S; Nielsen, J; Nigmanov, T; Nodulman, L; Norniella, O; Nurse, E; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Oldeman, R; Orava, R; Osterberg, K; Pagliarone, C; Palencia, E; Papadimitriou, V; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Piedra, J; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Portell, X; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ranjan, N; Rappoccio, S; Reisert, B; Rekovic, V; Renton, P; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Ruiz, A; Russ, J; Rusu, V; Saarikko, H; Sabik, S; Safonov, A; Sakumoto, W K; Salamanna, G; Saltó, O; Saltzberg, D; Sánchez, C; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savard, P; Savoy-Navarro, A; Scheidle, T; Schlabach, P; Schmidt, E E; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scott, A L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sfyrla, A; Shapiro, M D; Shears, T; Shepard, P F; Sherman, D; Shimojima, M; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Sjolin, J; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soderberg, M; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spinella, F; Spreitzer, T; Squillacioti, P; Stanitzki, M; Staveris-Polykalas, A; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Stuart, D; Suh, J S; Sukhanov, A; Sun, H; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Takikawa, K; Tanaka, M; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Thom, J; Thompson, A S; Thomson, E; Tipton, P; Tiwari, V; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Tourneur, S; Trischuk, W; Tseng, J; Tsuchiya, R; Tsuno, S; Turini, N; Ukegawa, F; Unverhau, T; Uozumi, S; Usynin, D; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Veramendi, G; Veszpremi, V; Vidal, R; Vila, I; Vilar, R; Vine, T; Vollrath, I; Volobouev, I; Volpi, G; Würthwein, F; Wagner, P; Wagner, R G; Wagner, R L; Wagner, J; Wagner, W; Wallny, R; Wang, S M; Warburton, A; Waschke, S; Waters, D; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Wynne, S M; Yagil, A; Yamamoto, K; Yamaoka, J; Yamashita, T; Yang, C; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zaw, I; Zhang, X; Zhou, J; Zucchelli, S

    2007-03-23

    We present the first observation of the baryon decay Lambda b0-->Lambda c+pi- followed by Lambda c+-->pK-pi+ in 106 pb-1 pp collisions at square root s=1.96 TeV in the CDF experiment. In order to reduce systematic error, the measured rate for Lambda b0 decay is normalized to the kinematically similar meson decay B0-->D+pi- followed by D+-->pi+K-pi+. We report the ratio of production cross sections (sigma) times the ratio of branching fractions (B) for the momentum region integrated above pT>6 GeV/c and pseudorapidity range |eta|<1.3: sigma(pp-->Lambda b0X)/sigma(pp-->B0X)xB(Lambda b0-->Lambda c+pi-)/B(B0-->D+pi-)=0.82+/-0.08(stat)+/-0.11(syst)+/-0.22[B(Lambda c+-->pK-pi+)].

  3. In vitro expression of Escherichia coli ribosomal protein genes: autogenous inhibition of translation.

    PubMed Central

    Yates, J L; Arfsten, A E; Nomura, M

    1980-01-01

    Escherichia coli ribosomal protein L1 (0.5 micro M) was found to inhibit the synthesis of both proteins of the L11 operon, L11 and L1, but not the synthesis of other proteins directed by lambda rifd 18 DNA. Similarly, S4 (1 micro M) selectively inhibited the synthesis of three proteins of the alpha operon, S13, S11, and S4, directed by lambda spcI DNA or a restriction enzyme fragment obtained from this DNA. S8 (3.6 micro M) also showed preferential inhibitory effects on the synthesis of some proteins encoded in the spc operon, L24 and L5 (and probably S14 and S8), directed by lambda spcl DNA or a restriction enzyme fragment carrying the genes for these proteins. The inhibitory effect of L1 was observed only with L1 and not with other proteins examined, including S4 and S8. Similarly, the effect of S4 was not observed with L1 or S8, and that of S8 was not seen with L1 or S4. Inhibition was shown to take place at the level of translation rather than transcription. Thus, at least some ribosomal proteins (L1 S4, and S8) have the ability to cause selective translational inhibition of the synthesis of certain ribosomal proteins whose genes are in the same operon as their own. These results support the hypothesis that certain free ribosomal proteins not assembled into ribosomes act as "autogenous" feedback inhibitors to regulate the synthesis of ribosomal proteins. Images PMID:6445562

  4. Georgia Tech Vertical Lift Research Center of Excellence

    DTIC Science & Technology

    2017-12-14

    Technical Project Summaries Task 1.1 (GT-1): Next Generation VABS for More Realistic Modeling of Composite Blades ...Methodology for the Prediction of Rotor Blade Ice Formation and Shedding ..................................................................... 20...software disclosures and technology transfer efforts. Task 1.1 (GT-1): Next Generation VABS for More Realistic Modeling of Composite Blades PIs

  5. Effects of Ex Vivo y-Tocopherol on Airway Macrophage ...

    EPA Pesticide Factsheets

    Elevated inflammation and altered immune responses are features found in atopic asthmatic airways. Recent studies indicate y-tocopherol (GT) supplementation can suppress airway inflammation in allergic asthma. We studied the effects of in vitro GT supplementation on receptor-mediated phagocytosis and expression of cell surface molecules associated with innate and adaptive immunity on sputum-derived macrophages. Cells from nonsmoking healthy (n = 6)and mild house dust mite-sensitive allergic asthmatics (n =6) were treated ex vivo with GT (300 uM) or saline (control). Phagocytosis of opsonized zymosan A bioparticles (Saccharomyces cerevisiae) and expression of surface molecules associated with innate and adaptive immunity were assessed using flow cytometry. GT caused significantly decreased (p < 0.05) internalization of attached zymosan bioparticles and decreased (p < 0.05) macrophage expression of CD206,CD36 and CD86 in allergic asthmatics but not in corntrols. Overall, GT caused down regulation of both innate and adaptive immune response elements, and atopic status appears to be an important factor. Recent studies on the effects of the fat-soluble steriod hormone vitamins D and E suggest that dietary suplementation with these vitamins may be helpful for the prevention or in the treatment of inflammatory and immune-mediated diseases, including atopic asthma.

  6. Grewia tiliaefolia and its active compound vitexin regulate the expression of glutamate transporters and protect Neuro2a cells from glutamate toxicity.

    PubMed

    Malar, Dicson Sheeja; Prasanth, Mani Iyer; Shafreen, Rajamohamed Beema; Balamurugan, Krishnaswamy; Devi, Kasi Pandima

    2018-04-25

    Glutamate is a major neurotransmitter involved in several brain functions and glutamate excitotoxicity is involved in Alzheimer's disease (AD). In the current study, the neuroprotective effect of the Indian medicinal plant Grewia tiliaefolia (GT) and its active component vitexin was evaluated in Neuro-2a cells against glutamate toxicity. Neuro-2a cells were exposed to glutamate to cause excitotoxicity and the neuroprotective effect of GT and vitexin were evaluated using biochemical studies (estimation of reactive oxygen species, reactive nitrogen species, protein carbonyl content, lipid peroxidation level, mitochondrial membrane potential and caspase-3 activity), molecular docking studies, gene expression and western blot analysis. Glutamate exposure to Neuro-2a cells induced oxidative stress, loss of membrane potential, suppressed the expression of antioxidant response genes (Nrf-2, HO-1, NQO-1), glutamate transporters (GLAST-1, GLT-1) and induced the expression of NMDAR, Calpain. However, pre-treatment of cells with GT/vitexin inhibited oxidative stress mediated damage by augmenting the expression of Nrf-2/HO-1 pathway, inducing the expression of glutamate transporters and downregulating Calpain, NMDAR. Molecular docking showed that vitexin effectively binds to NMDAR and GSK-3β and thereby can inhibit their activation. GT/vitexin also inhibited glutamate induced Bax expression. Methanol extract of G. tiliaefolia and its active component vitexin can act in an antioxidant dependent mechanism as well as by regulating glutamate in mitigating the toxicity exerted by glutamate in Neuro-2a cells. Our results conclude that GT/vitexin can act as potential drug leads for the therapeutic intervention of AD. Copyright © 2017. Published by Elsevier Inc.

  7. Evidence for Conserved Function of γ–Glutamyltranspeptidase in Helicobacter Genus

    PubMed Central

    Revez, Joana; Javed, Sundus; El-Najjar, Nahed; Anderl, Florian; Hyytiäinen, Heidi; Vuorela, Pia; Gerhard, Markus; Hänninen, Marja-Liisa

    2012-01-01

    The confounding consequences of Helicobacter bilis infection in experimental mice populations are well recognized, but the role of this bacterium in human diseases is less known. Limited data are available on virulence determinants of this species. In Helicobacter pylori, γ-glutamyltranspeptidase (γGT) contributes to the colonization of the gastric mucosa and to the pathogenesis of peptic ulcer. The role of γGT in H. bilis infections remains unknown. The annotated genome sequence of H. bilis revealed two putative ggt genes and our aim was to characterize these H. bilis γGT paralogues. We performed a phylogenetic analysis to understand the evolution of Helicobacter γGTs and to predict functional activities of these two genes. In addition, both copies of H. bilis γGTs were expressed as recombinant proteins and their biochemical characteristics were analysed. Functional complementation of Esherichia coli deficient in γGT activity and deletion of γGT in H. bilis were performed. Finally, the inhibitory effect of T-cell and gastric cell proliferation by H. bilis γGT was assessed. Our results indicated that one gene is responsible for γGT activity, while the other showed no γGT activity due to lack of autoprocessing. Although both H. bilis and H. pylori γGTs exhibited a similar affinity to L-Glutamine and γ-Glutamyl-p-nitroanilide, the H. bilis γGT was significantly less active. Nevertheless, H. bilis γGT inhibited T-cell proliferation at a similar level to that observed for H. pylori. Finally, we showed a similar suppressive influence of both H. bilis and H. pylori γGTs on AGS cell proliferation mediated by an apoptosis-independent mechanism. Our data suggest a conserved function of γGT in the Helicobacter genus. Since γGT is present only in a few enterohepatic Helicobacter species, its expression appears not to be essential for colonization of the lower gastrointestinal tract, but it could provide metabolic advantages in colonization capability of different niches. PMID:22348013

  8. Lambda cyhalothrin toxicity induces alterations in lipogenic genes and inflammatory factors in rat liver.

    PubMed

    Moustafa, Gihan G; Hussein, Mohamed M A

    2016-02-01

    The present study aims to elucidate the molecular basis of lambda cyhalothrin (LCT) toxicity. Thirty-two mature male albino rats were randomly classified into four equal groups. The first group was orally administered normal saline, the second group was orally administered dimethylsulfoxide (DMSO). The third group was orally administered 1/100 LD50 (6.12 mg/kg b. wt) of a commercial formulation containing 2.5% LCT (i.e., a net dose LCT corresponding to 0.15 mg/kg b. wt). The fourth group was orally administered 1/100 LD50 (0.64 mg/kg b. wt) of a pure form of LCT. The results indicated that exposure to LCT is capable of inducing an up-regulation in the mRNA expression levels of peroxisome proliferative activated receptor α and γ (PPAR α and PPAR γ), tumor necrosis factor (TNF-α), fatty acid synthase (FAS) and sterol regulatory element binding protein-1c (SREBP-1c). Additionally, our study revealed a significant increase in serum levels of ALT, AST, ALP, γGT as well as the inflammatory cytokines TNF-α and monocyte chemoattractant protein-1 (MCP-1). A significant elevation in total lipids, total cholesterol, triacylglycerol, LDL-c and leptin with a corresponding significant decrease in HDL-c was also noted. Moreover, our results depicted that LCT treatment exhibits a significant increase in hepatic MDA levels concurrent with a significant decrease in GSH levels and the activities of CAT, SOD, and GPx. An immunohistochemical investigation also revealed a strong up-regulation of hepatic FAS in the LCT treated groups. The histopathological findings were marked by evidence in support of periportal fatty changes and interstitial aggregation of round cells.

  9. Gender role models in fictional novels for emerging adult lesbians.

    PubMed

    Cook, Jennifer R; Rostosky, Sharon S; Riggle, Ellen D B

    2013-01-01

    Novels provide role models for young adult lesbians and thus may influence their identity development. This study focused on 16 lesbian protagonists identified in 11 young adult novels that received 2011 Lambda Literary Award nominations. Content analyses revealed six themes. Three themes defied traditional gender stereotypes: Asserting Oneself, Pursuing Intimacy with Another Woman, and Breaking Free of Constraints to Authentic Self-Expression. Three themes reinforced gender stereotypes: Negative Emotional Experiences Associated with Lesbian Identity, Traditional Masculine Gender Expression, and Traditional Gender Role-Based Sexual Scripts. Each theme is discussed in light of its possible contribution to lesbian identity development.

  10. Anti-inflammatory and heme oxygenase-1 inducing activities of lanostane triterpenes isolated from mushroom Ganoderma lucidum in RAW264.7 cells

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

    Choi, Solip; Nguyen, Van Thu; Tae, Nara

    Ganoderma lucidum is a popular medicinal mushroom used in traditional medicine for preventing or treating a variety of diseases. In the present study, we investigated the anti-inflammatory and heme oxygenase (HO)-1 inducing effects of 12 lanostane triterpenes from G. lucidum in RAW264.7 cells. Of these, seven triterpenes, butyl lucidenateE{sub 2}, butyl lucidenateD{sub 2} (GT-2), butyl lucidenate P, butyl lucidenateQ, Ganoderiol F, methyl ganodenate J and butyl lucidenate N induced HO-1 expression and suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO) production. Inhibiting HO-1 activity abrogated the inhibitory effects of these triterpenes on the production of NO in LPS-stimulated RAW264.7 cells, suggesting themore » involvement of HO-1 in the anti-inflammatory effects of these triterpenes. We further studied the anti-inflammatory and HO-1 inducing effects of GT-2. Mitogen-activated protein kinase inhibitors or N-acetylcysteine, an antioxidant, did not suppress GT-2-mediated HO-1 induction; however, LY294002, a phosphoinositide 3-kinase (PI3K) inhibitor, blocked GT-2-induced HO-1 mRNA and protein expression. GT-2 increased nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and knockdown of Nrf2 by small interfering RNA blocked GT-2-mediated HO-1 induction, suggesting that GT-2 induced HO-1 expression via the PI3K/AKT-Nrf2 pathway. Consistent with the notion that HO-1 has anti-inflammatory properties, GT-2 inhibited the production of tumor necrosis factor-α and interleukin-6, as well as inducible nitric oxide synthase and cyclooxygenase-2 expression. These findings suggest that HO-1 inducing activities of these lanostane triterpenes may be important in the understanding of a novel mechanism for the anti-inflammatory activity of G. lucidum. - Highlights: • The anti-inflammatory effects of selected triterpenes from Ganoderma lucidum are demonstrated. • Heme oxygenase-1 induction is attributable to the anti-inflammatory properties of these triterpenes. • The triterpenes induce heme oxygenase-1 expression via the AKT-Nrf2 pathway. • The mechanism explains the anti-inflammatory effect of triterpenes from G. lucidum.« less

  11. Phosphorylated Protein Kinase C (Zeta/Lambda) Expression in Colorectal Adenocarcinoma and Its Correlation with Clinicopathologic Characteristics and Prognosis.

    PubMed

    Yeo, Min-Kyung; Kim, Ji Yeon; Seong, In-Ock; Kim, Jin-Man; Kim, Kyung-Hee

    2017-01-01

    Background: Protein kinase C zeta/lambda (PKCζ/λ) is a family of protein kinase enzymes that contributes to cell proliferation and regulation, which are important for cancer development. PKCζ/λ has been shown to be an important regulator of tumorigenesis in intestinal cancer. The phosphorylated form of PKCζ/λ, p-PKCζ/λ, is suggested as an active form of PKCζ/λ. However, p-PKCζ/λ expression and its clinicopathologic implication in colorectal adenocarcinoma (CRAC) are unclear. Methods: Seven whole-tissue sections of malignant polyps containing both non-neoplastic and neoplastic mucosa, 11 adenomas with low-grade dysplasia, and 173 CRACs were examined by immunohistochemistry and western blot assay for p-PKCζ/λ protein expression. The association of p-PKCζ/λ expression with clinicopathologic factors including patient survival was studied. Results: In non-neoplastic epithelia, p-PKCζ/λ showed a weak cytoplasmic immunostaining. Adenomas and CRACs demonstrated up-regulated p-PKCζ/λ detection. Cytoplasmic p-PKCζ/λ expression was higher in CRAC than in adenoma. In CRACs, p-PKCζ/λ expression was inversely correlated with pathologic TNM stage (I-II versus III-IV) and poor differentiation. Statistical correlations between low expression of p-PKCζ/λ with shortened overall survival and disease-free survival were seen (p=0.004 and p=0.034, respectively). Conclusions: P-PKCζ/λ overexpression is implicated in tumorigenesis but down-regulation was a poor prognostic factor in CRAC.

  12. The role of N1 domain on the activity, stability, substrate specificity and raw starch binding of amylopullulanase of the extreme thermophile Geobacillus thermoleovorans.

    PubMed

    Nisha, M; Satyanarayana, T

    2015-07-01

    In order to understand the role of N1 domain (1-257 aa) in the amylopullulanase (gt-apu) of the extremely thermophilic bacterium Geobacillus thermoleovorans NP33, N1 deletion construct (gt-apuΔN) has been generated and expressed in Escherichia coli. The truncated amylopullulanase (gt-apuΔN) exhibits similar pH and temperature optima like gt-apu, but enhanced thermostability. The gt-apuΔN has greater hydrolytic action and specific activity on pullulan than gt-apu. The k cat (starch and pullulan) and K m (starch) values of gt-apuΔN increased, while K m (pullulan) decreased. The enzyme upon N1 deletion hydrolyzed maltotetraose as the smallest substrate in contrast to maltopentaose of gt-apu. The role of N1 domain of gt-apu in raw starch binding has been confirmed, for the first time, based on deletion and Langmuir-Hinshelwood kinetics. Furthermore, N1 domain appears to exert a negative influence on the thermostability of gt-apu because N1 truncation significantly improves thermostability.

  13. GAPTrap: A Simple Expression System for Pluripotent Stem Cells and Their Derivatives.

    PubMed

    Kao, Tim; Labonne, Tanya; Niclis, Jonathan C; Chaurasia, Ritu; Lokmic, Zerina; Qian, Elizabeth; Bruveris, Freya F; Howden, Sara E; Motazedian, Ali; Schiesser, Jacqueline V; Costa, Magdaline; Sourris, Koula; Ng, Elizabeth; Anderson, David; Giudice, Antonietta; Farlie, Peter; Cheung, Michael; Lamande, Shireen R; Penington, Anthony J; Parish, Clare L; Thomson, Lachlan H; Rafii, Arash; Elliott, David A; Elefanty, Andrew G; Stanley, Edouard G

    2016-09-13

    The ability to reliably express fluorescent reporters or other genes of interest is important for using human pluripotent stem cells (hPSCs) as a platform for investigating cell fates and gene function. We describe a simple expression system, designated GAPTrap (GT), in which reporter genes, including GFP, mCherry, mTagBFP2, luc2, Gluc, and lacZ are inserted into the GAPDH locus in hPSCs. Independent clones harboring variations of the GT vectors expressed remarkably consistent levels of the reporter gene. Differentiation experiments showed that reporter expression was reliably maintained in hematopoietic cells, cardiac mesoderm, definitive endoderm, and ventral midbrain dopaminergic neurons. Similarly, analysis of teratomas derived from GT-lacZ hPSCs showed that β-galactosidase expression was maintained in a spectrum of cell types representing derivatives of the three germ layers. Thus, the GAPTrap vectors represent a robust and straightforward tagging system that enables indelible labeling of PSCs and their differentiated derivatives. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Cloning, sequencing, and expression of the gene coding for bile acid 7 alpha-hydroxysteroid dehydrogenase from Eubacterium sp. strain VPI 12708.

    PubMed Central

    Baron, S F; Franklund, C V; Hylemon, P B

    1991-01-01

    Southern blot analysis indicated that the gene encoding the constitutive, NADP-linked bile acid 7 alpha-hydroxysteroid dehydrogenase of Eubacterium sp. strain VPI 12708 was located on a 6.5-kb EcoRI fragment of the chromosomal DNA. This fragment was cloned into bacteriophage lambda gt11, and a 2.9-kb piece of this insert was subcloned into pUC19, yielding the recombinant plasmid pBH51. DNA sequence analysis of the 7 alpha-hydroxysteroid dehydrogenase gene in pBH51 revealed a 798-bp open reading frame, coding for a protein with a calculated molecular weight of 28,500. A putative promoter sequence and ribosome binding site were identified. The 7 alpha-hydroxysteroid dehydrogenase mRNA transcript in Eubacterium sp. strain VPI 12708 was about 0.94 kb in length, suggesting that it is monocistronic. An Escherichia coli DH5 alpha transformant harboring pBH51 had approximately 30-fold greater levels of 7 alpha-hydroxysteroid dehydrogenase mRNA, immunoreactive protein, and specific activity than Eubacterium sp. strain VPI 12708. The 7 alpha-hydroxysteroid dehydrogenase purified from the pBH51 transformant was similar in subunit molecular weight, specific activity, and kinetic properties to that from Eubacterium sp. strain VPI 12708, and it reached with antiserum raised against the authentic enzyme on Western immunoblots. Alignment of the amino acid sequence of the 7 alpha-hydroxysteroid dehydrogenase with those of 10 other pyridine nucleotide-linked alcohol/polyol dehydrogenases revealed six conserved amino acid residues in the N-terminal regions thought to function in coenzyme binding. Images PMID:1856160

  15. The cDNA sequence of mouse Pgp-1 and homology to human CD44 cell surface antigen and proteoglycan core/link proteins.

    PubMed

    Wolffe, E J; Gause, W C; Pelfrey, C M; Holland, S M; Steinberg, A D; August, J T

    1990-01-05

    We describe the isolation and sequencing of a cDNA encoding mouse Pgp-1. An oligonucleotide probe corresponding to the NH2-terminal sequence of the purified protein was synthesized by the polymerase chain reaction and used to screen a mouse macrophage lambda gt11 library. A cDNA clone with an insert of 1.2 kilobases was selected and sequenced. In Northern blot analysis, only cells expressing Pgp-1 contained mRNA species that hybridized with this Pgp-1 cDNA. The nucleotide sequence of the cDNA has a single open reading frame that yields a protein-coding sequence of 1076 base pairs followed by a 132-base pair 3'-untranslated sequence that includes a putative polyadenylation signal but no poly(A) tail. The translated sequence comprises a 13-amino acid signal peptide followed by a polypeptide core of 345 residues corresponding to an Mr of 37,800. Portions of the deduced amino acid sequence were identical to those obtained by amino acid sequence analysis from the purified glycoprotein, confirming that the cDNA encodes Pgp-1. The predicted structure of Pgp-1 includes an NH2-terminal extracellular domain (residues 14-265), a transmembrane domain (residues 266-286), and a cytoplasmic tail (residues 287-358). Portions of the mouse Pgp-1 sequence are highly similar to that of the human CD44 cell surface glycoprotein implicated in cell adhesion. The protein also shows sequence similarity to the proteoglycan tandem repeat sequences found in cartilage link protein and cartilage proteoglycan core protein which are thought to be involved in binding to hyaluronic acid.

  16. Major Trypanosoma cruzi antigenic determinant in Chagas' heart disease shares homology with the systemic lupus erythematosus ribosomal P protein epitope.

    PubMed Central

    Mesri, E A; Levitus, G; Hontebeyrie-Joskowicz, M; Dighiero, G; Van Regenmortel, M H; Levin, M J

    1990-01-01

    A Trypanosoma cruzi lambda gt11 cDNA clone, JL5, expressed a recombinant protein which was found to react predominantly with chronic Chagas' heart disease sera. The cloned 35-residue-long peptide was identified as the carboxyl-terminal portion of a T. cruzi ribosomal P protein. The JL5 13 carboxyl-terminal residues shared a high degree of homology with the systemic lupus erythematosus (SLE) ribosomal P protein epitope. Synthetic peptides comprising the 13 (R-13), 10 (R-10), and 7 (R-7) carboxyl-terminal residues of the JL5 protein were used to study, by enzyme-linked immunosorbent assay, the specificity of the Chagas' disease anti-JL5 and SLE anti-P antibodies. The R-13 peptide defined a linear antigenic determinant of the JL5 recombinant protein. As was proved for JL5, R-13 defined antibody specificities which were significantly increased in chronic Chagas' heart disease patients. Only SLE anti-P positive sera were found to react with JL5 and R-13. Fine epitope mapping showed that Chagas' disease anti-JL5 and SLE anti-P antibodies define similar epitopes within the R-13 peptide. The binding of the SLE sera to JL5 was completely blocked by the R-13 peptide, indicating that the shared specificity between anti-JL5 and anti-P autoantibodies was exclusively limited to the conserved linear epitope(s) within the R-13 peptide. The prevalence of high anti-R-13 antibody titers in Chagas' heart disease patients supports the hypothesis that postulates the existence of autoimmune disorders in Chagas' heart disease. PMID:1696282

  17. Altered Expression of Genes Implicated in Xylan Biosynthesis Affects Penetration Resistance against Powdery Mildew.

    PubMed

    Chowdhury, Jamil; Lück, Stefanie; Rajaraman, Jeyaraman; Douchkov, Dimitar; Shirley, Neil J; Schwerdt, Julian G; Schweizer, Patrick; Fincher, Geoffrey B; Burton, Rachel A; Little, Alan

    2017-01-01

    Heteroxylan has recently been identified as an important component of papillae, which are formed during powdery mildew infection of barley leaves. Deposition of heteroxylan near the sites of attempted fungal penetration in the epidermal cell wall is believed to enhance the physical resistance to the fungal penetration peg and hence to improve pre-invasion resistance. Several glycosyltransferase (GT) families are implicated in the assembly of heteroxylan in the plant cell wall, and are likely to work together in a multi-enzyme complex. Members of key GT families reported to be involved in heteroxylan biosynthesis are up-regulated in the epidermal layer of barley leaves during powdery mildew infection. Modulation of their expression leads to altered susceptibility levels, suggesting that these genes are important for penetration resistance. The highest level of resistance was achieved when a GT43 gene was co-expressed with a GT47 candidate gene, both of which have been predicted to be involved in xylan backbone biosynthesis. Altering the expression level of several candidate heteroxylan synthesis genes can significantly alter disease susceptibility. This is predicted to occur through changes in the amount and structure of heteroxylan in barley papillae.

  18. Liquid-air partition coefficients of 1,1-difluoroethane (HFC152a), 1,1,1-trifluoroethane (HFC143a), 1,1,1,2-tetrafluoroethane (HFC134a), 1,1,1,2,2-pentafluoroethane (HFC125) and 1,1,1,3,3-pentafluoropropane (HFC245fa).

    PubMed

    Ernstgård, Lena; Lind, Birger; Andersen, Melvin E; Johanson, Gunnar

    2010-01-01

    Blood-air and tissue-blood coefficients (lambda) are essential to characterize the uptake and disposition of volatile substances, e.g. by physiologically based pharmacokinetic (PBPK) modelling. Highly volatile chemicals, including many hydrofluorocarbons (HFC) have low solubility in liquid media. These characteristics pose challenges for determining lambda values. A modified head-space vial equilibrium method was used to determine lambda values for five widely used HFCs. The method is based on automated head-space gas chromatography and injection of equal amount of chemical in two head-space vials with identical air phase volumes but different volumes of the liquid phase. The liquids used were water (physiological saline), fresh human blood, and olive oil. The average lambda values (n = 8) were as follows: 1,1-difluoroethane (HFC152a) - 1.08 (blood-air), 1.11 (water-air) and 5.6 (oil-air); 1,1,1-trifluoroethane (HFC143a) - 0.15, 0.15 and 1.90; 1,1,1,2-tetrafluoroethane (HFC134a) - 0.36, 0.35 and 3.5; 1,1,1,2,2-pentafluoroethane (HFC125) - 0.083, 0.074 and 1.71; and 1,1,1,3,3-pentafluoropropane (HFC245fa) - 0.62, 0.58 and 12.1. The lambda values appeared to be concentration-independent in the investigated range (2-200 ppm). In spite of the low lambda values, the method errors were modest, with coefficients of variation of 9, 11 and 10% for water, blood and oil, respectively.

  19. Thrombomodulin Contributes to Gamma Tocotrienol-Mediated Lethality Protection and Hematopoietic Cell Recovery in Irradiated Mice

    PubMed Central

    Pathak, Rupak; Shao, Lijian; Ghosh, Sanchita P.; Zhou, Daohong; Boerma, Marjan; Weiler, Hartmut; Hauer-Jensen, Martin

    2015-01-01

    Systemic administration of recombinant thrombomodulin (TM) confers radiation protection partly by accelerating hematopoietic recovery. The uniquely potent radioprotector gamma tocotrienol (GT3), in addition to being a strong antioxidant, inhibits the enzyme hydroxy-methyl-glutaryl-coenzyme A reductase (HMGCR) and thereby likely modulates the expression of TM. We hypothesized that the mechanism underlying the exceptional radioprotective properties of GT3 partly depends on the presence of endothelial TM. In vitro studies confirmed that ionizing radiation suppresses endothelial TM (about 40% at 4 hr after 5 Gy γ-irradiation) and that GT3 induces TM expression (about 2 fold at the mRNA level after 5 μM GT3 treatment for 4 hr). In vivo survival studies showed that GT3 was significantly more effective as a radioprotector in TM wild type (TM+/+) mice than in mice with low TM function (TMPro/-). After exposure to 9 Gy TBI, GT3 pre-treatment conferred 85% survival in TM+/+ mice compared to only 50% in TMPro/-. Thus, GT3-mediated radiation lethality protection is partly dependent on endothelial TM. Significant post-TBI recovery of hematopoietic cells, particularly leukocytes, was observed in TM+/+ mice (p = 0.003), but not in TMPro/- mice, despite the fact that GT3 induced higher levels of granulocyte colony stimulating factor (G-CSF) in TMPro/- mice (p = 0.0001). These data demonstrate a critical, G-CSF-independent, role for endothelial TM in GT3-mediated lethality protection and hematopoietic recovery after exposure to TBI and may point to new strategies to enhance the efficacy of current medical countermeasures in radiological/nuclear emergencies. PMID:25860286

  20. [Spectral emissivity of thin films].

    PubMed

    Zhong, D

    2001-02-01

    In this paper, the contribution of multiple reflections in thin film to the spectral emissivity of thin films of low absorption is discussed. The expression of emissivity of thin films derived here is related to the thin film thickness d and the optical constants n(lambda) and k(lambda). It is shown that in the special case d-->infinity the emissivity of thin films is equivalent to that of the bulk material. Realistic numerical and more precise general numerical results for the dependence of the emissivity on d, n(lambda) and k(lambda) are given.

  1. The modelled surface mass balance of the Antarctic Peninsula at 5.5 km horizontal resolution

    NASA Astrophysics Data System (ADS)

    van Wessem, J. M.; Ligtenberg, S. R. M.; Reijmer, C. H.; van de Berg, W. J.; van den Broeke, M. R.; Barrand, N. E.; Thomas, E. R.; Turner, J.; Wuite, J.; Scambos, T. A.; van Meijgaard, E.

    2015-09-01

    This study presents a high-resolution (~ 5.5 km) estimate of Surface Mass Balance (SMB) over the period 1979-2014 for the Antarctic Peninsula (AP), generated by the regional atmospheric climate model RACMO2.3 and a Firn Densification Model (FDM). RACMO2.3 is used to force the FDM, which calculates processes in the snowpack, such as meltwater percolation, refreezing and runoff. We evaluate model output with 132 in-situ SMB observations and discharge rates from 6 glacier drainage basins, and find that the model realistically simulates the strong spatial variability in precipitation, but that significant biases remain as a result of the highly complex topography of the AP. It is also clear that the observations significantly underrepresent the high-accumulation regimes. The SMB map reveals large accumulation gradients, with precipitation values above 3000 mm we yr-1 over the western AP (WAP) and below 500 mm we yr-1 on the eastern AP (EAP), not resolved by coarser data-sets such as ERA-Interim. The other SMB components are one order of magnitude smaller, with drifting snow sublimation the largest ablation term removing up to 100 mm we yr-1 of mass. Snowmelt is widespread over the AP, reaching 500 mm we yr-1 towards the northern ice shelves, but the meltwater mostly refreezes. As a result runoff fluxes are low, but still considerable (200 mm we yr-1) over the Larsen (B/C), Wilkins and George VI ice shelves. The average AP ice sheet integrated SMB, including ice shelves (an area of 4.1 × 105 km2), is estimated at 351 Gt yr-1 with an interannual variability of 58 Gt yr-1, which is dominated by precipitation (PR) (365 ± 57 Gt yr-1). The WAP (2.4 × 105 km2) SMB (276 ± 47 Gt yr-1), where PR is large (276 ± 47 Gt yr-1), dominates over the EAP (1.7 × 105 km2) SMB (75 ± 11 Gt yr-1) and PR (84 ± 11 Gt yr-1). Total sublimation is 11 ± 2 Gt yr-1 and meltwater runoff into the ocean is 4 ± 4 Gt yr-1. There are no significant trends in any of the AP SMB components, except for snowmelt that shows a significant decrease over the last 36 years (-0.36 Gt yr-2).

  2. Cholinergic dysfunctions and enhanced oxidative stress in the neurobehavioral toxicity of lambda-cyhalothrin in developing rats.

    PubMed

    Ansari, Reyaz W; Shukla, Rajendra K; Yadav, Rajesh S; Seth, Kavita; Pant, Aditya B; Singh, Dhirendra; Agrawal, Ashok K; Islam, Fakhrul; Khanna, Vinay K

    2012-11-01

    This study is focused on understanding the mechanism of neurobehavioral toxicity of lambda-cyhalothrin, a new generation type II synthetic pyrethroid in developing rats following their exposure from post-lactational day (PLD)22 to PLD49 and investigate whether neurobehavioral alterations are transient or persistent. Post-lactational exposure to lambda-cyhalothrin (1.0 or 3.0 mg/kg body weight, p.o.) affected grip strength and learning activity in rats on PLD50 and the persistent impairment of grip strength and learning was observed at 15 days after withdrawal of exposure on PLD65. A decrease in the binding of muscarinic-cholinergic receptors in frontocortical, hippocampal, and cerebellar membranes associated with decreased expression of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in hippocampus was observed following exposure to lambda-cyhalothrin on PLD50 and PLD65. Exposure to lambda-cyhalothrin was also found to increase the expression of growth-associated protein-43 in hippocampus of rats on PLD50 and PLD65 as compared to controls. A significant increase in lipid peroxidation and protein carbonyl levels and decreased levels of reduced glutathione and activity of superoxide dismutase, catalase, and glutathione peroxidase in brain regions of lambda-cyhalothrin exposed rats were distinctly observed indicating increased oxidative stress. Inhibition of ChAT and AChE activity may cause down-regulation of muscarinic-cholinergic receptors consequently impairing learning activity in developing rats exposed to lambda-cyhalothrin. The data further indicate that long-term exposure to lambda-cyhalothrin at low doses may be detrimental and changes in selected behavioral and neurochemical end points may persist if exposure to lambda-cyhalothrin continues.

  3. Glutathione S-conjugates as prodrugs to target drug-resistant tumors

    PubMed Central

    Ramsay, Emma E.; Dilda, Pierre J.

    2014-01-01

    Living organisms are continuously exposed to xenobiotics. The major phase of enzymatic detoxification in many species is the conjugation of activated xenobiotics to reduced glutathione (GSH) catalyzed by the glutathione-S-transferase (GST). It has been reported that some compounds, once transformed into glutathione S-conjugates, enter the mercapturic acid pathway whose end products are highly reactive and toxic for the cell responsible for their production. The cytotoxicity of these GSH conjugates depends essentially on GST and gamma-glutamyl transferases (γGT), the enzymes which initiate the mercapturic acid synthesis pathway. Numerous studies support the view that the expression of GST and γGT in cancer cells represents an important factor in the appearance of a more aggressive and resistant phenotype. High levels of tumor GST and γGT expression were employed to selectively target tumor with GST- or γGT-activated drugs. This strategy, explored over the last two decades, has recently been successful using GST-activated nitrogen mustard (TLK286) and γGT-activated arsenic-based (GSAO and Darinaparsin) prodrugs confirming the potential of GSH-conjugates as anticancer drugs. PMID:25157234

  4. Epigenetic effects of green tea polyphenols in cancer

    PubMed Central

    Henning, Susanne M; Wang, Piwen; Carpenter, Catherine L; Heber, David

    2014-01-01

    Epigenetics describes heritable alterations of gene expression and chromatin organization without changes in DNA sequence. Both hypermethylation and hypomethylation of DNA can affect gene expression and the multistep process of carcinogenesis. Epigenetic changes are reversible and may be targeted by dietary interventions. Bioactive compounds from green tea (GT) such as (–)-epigallocatechin gallate have been shown to alter DNA methyltransferase activity in studies of esophageal, oral, skin, Tregs, lung, breast and prostate cancer cells, which may contribute to the chemopreventive effect of GT. Three out of four mouse model studies have confirmed the inhibitory effect of (–)-epigallocatechin gallate on DNA methylation. A human study demonstrated that decreased methylation of CDX2 and BMP-2 in gastric carcinoma was associated with higher GT consumption. It is the goal of this review to summarize our current knowledge of the potential of GT to alter epigenetic processes, which may be useful in chemoprevention. PMID:24283885

  5. [Construction of Plasmodium falciparum signal peptide peptidase-GFP mutant and its expression analysis in the malaria parasite].

    PubMed

    Li, Xue-rong; Wu, Yin-juan; Shang, Mei; Li, Ye; Xu, Jin; Yu, Xin-bing; Athar, Chishti

    2014-08-01

    To construct recombinant plasmid pSPPcGT which contains signal peptide peptidase gene of Plasmodium falciparum (PJSPP) and GFP, and transfect into P. falciparum (3D7 strain) to obtain mutant parasites which can express PJSPP-GFP. Plasmodium falciparum(3D7 strain) genomic DNA was extracted from cultured malaria parasites. The C-terminal region of PJSPP, an 883 bp gene fragment was amplified by PCR, and then cloned into pPM2GT vector to get recombinant vector pSPPcGT. The recombinant vectors were identified by PCR, double restriction enzyme digestion and DNA sequencing. pSPPcGT vector was transfected into malaria parasites. The positive clones were selected by adding inhibitor of Plasmodium falciparum dihydrofolate reductase WR99210 to the culture medium. The pSPP-GFP-transfected parasites were fixed with methanol, stained with DAPI, and observed under immunofluorescence microscope. The PJSPP-GFP expression in P. falciparum was identified by SDS-PAGE and Western blotting. The C-terminal region of PJSPP was amplified from P.falciparum (3D7 strain) genomic DNA by PCR with the length of 883 bp. The constructed recombinant vectors were identified by PCR screening, double restriction enzyme digestion and DNA sequencing. The pSPPcGT vector was transfected into P. falciparum and the positive clones were selected by WR99210. GFP fluorescence was observed in transfected parasites by immunofluorescence microscopy, and mainly located in the cytoplasm. The PJSPP-GFP expression in malaria parasites was confirmed by Western blotting with a relative molecular mass of Mr 64,000. Recombinant vector PJSPP-GFP is constructed and transfected into P. falciparum to obtain P. falciparum mutant clone which can express PfSPP-GFP.

  6. Biochemical and Molecular Characterization of a Flavonoid 3-O-glycosyltransferase Responsible for Anthocyanins and Flavonols Biosynthesis in Freesia hybrida

    PubMed Central

    Sun, Wei; Liang, Lingjie; Meng, Xiangyu; Li, Yueqing; Gao, Fengzhan; Liu, Xingxue; Wang, Shucai; Gao, Xiang; Wang, Li

    2016-01-01

    The glycosylation of flavonoids increases their solubility and stability in plants. Flowers accumulate anthocyanidin and flavonol glycosides which are synthesized by UDP-sugar flavonoid glycosyltransferases (UFGTs). In our previous study, a cDNA clone (Fh3GT1) encoding UFGT was isolated from Freesia hybrida, which was preliminarily proved to be invovled in cyanidin 3-O-glucoside biosynthesis. Here, a variety of anthocyanin and flavonol glycosides were detected in flowers and other tissues of F. hybrida, implying the versatile roles of Fh3GT1 in flavonoids biosynthesis. To further unravel its multi-functional roles, integrative analysis between gene expression and metabolites was investigated. The results showed expression of Fh3GT1 was positively related to the accumulation of anthocyanins and flavonol glycosides, suggesting its potential roles in the biosynthesis of both flavonoid glycosides. Subsequently, biochemical analysis results revealed that a broad range of flavonoid substrates including flavonoid not naturally occurred in F. hybrida could be recognized by the recombinant Fh3GT1. Both UDP-glucose and UDP-galactose could be used as sugar donors by recombinant Fh3GT1, although UDP-galactose was transferred with relatively low activity. Furthermore, regiospecificity analysis demonstrated that Fh3GT1 was able to glycosylate delphinidin at the 3-, 4-′, and 7- positions in a sugar-dependent manner. And the introduction of Fh3GT1 into Arabidopsis UGT78D2 mutant successfully restored the anthocyanins and flavonols phenotypes caused by lost-of-function of the 3GT, indicating that Fh3GT1 functions as a flavonoid 3-O-glucosyltransferase in vivo. In summary, these results demonstrate that Fh3GT1 is a flavonoid 3-O-glycosyltransferase using UDP-glucose as the preferred sugar donor and may involve in flavonoid glycosylation in F. hybrida. PMID:27064818

  7. Biochemical and Molecular Characterization of a Flavonoid 3-O-glycosyltransferase Responsible for Anthocyanins and Flavonols Biosynthesis in Freesia hybrida.

    PubMed

    Sun, Wei; Liang, Lingjie; Meng, Xiangyu; Li, Yueqing; Gao, Fengzhan; Liu, Xingxue; Wang, Shucai; Gao, Xiang; Wang, Li

    2016-01-01

    The glycosylation of flavonoids increases their solubility and stability in plants. Flowers accumulate anthocyanidin and flavonol glycosides which are synthesized by UDP-sugar flavonoid glycosyltransferases (UFGTs). In our previous study, a cDNA clone (Fh3GT1) encoding UFGT was isolated from Freesia hybrida, which was preliminarily proved to be invovled in cyanidin 3-O-glucoside biosynthesis. Here, a variety of anthocyanin and flavonol glycosides were detected in flowers and other tissues of F. hybrida, implying the versatile roles of Fh3GT1 in flavonoids biosynthesis. To further unravel its multi-functional roles, integrative analysis between gene expression and metabolites was investigated. The results showed expression of Fh3GT1 was positively related to the accumulation of anthocyanins and flavonol glycosides, suggesting its potential roles in the biosynthesis of both flavonoid glycosides. Subsequently, biochemical analysis results revealed that a broad range of flavonoid substrates including flavonoid not naturally occurred in F. hybrida could be recognized by the recombinant Fh3GT1. Both UDP-glucose and UDP-galactose could be used as sugar donors by recombinant Fh3GT1, although UDP-galactose was transferred with relatively low activity. Furthermore, regiospecificity analysis demonstrated that Fh3GT1 was able to glycosylate delphinidin at the 3-, 4-', and 7- positions in a sugar-dependent manner. And the introduction of Fh3GT1 into Arabidopsis UGT78D2 mutant successfully restored the anthocyanins and flavonols phenotypes caused by lost-of-function of the 3GT, indicating that Fh3GT1 functions as a flavonoid 3-O-glucosyltransferase in vivo. In summary, these results demonstrate that Fh3GT1 is a flavonoid 3-O-glycosyltransferase using UDP-glucose as the preferred sugar donor and may involve in flavonoid glycosylation in F. hybrida.

  8. Criminality in Greece during the years of financial crisis: 2008-2014.

    PubMed

    Tsouvelas, G; Konstantakopoulos, G; Vakirtzis, A; Giotakos, O; Papaslanis, T; Kontaxakis, V

    2018-01-01

    The link between poverty, unemployment and economic downturns and increases in crime rates has long been the subject of social science study. However, the relationships between these phenomena has not been studied sufficiently and through time in most European countries that suffered, or, like Greece, are still suffering the recent financial crisis. We examined if the recent financial crisis in Greece has coincided with an increase in crime, analyzing crime rates since the start of the financial crisis and over an extensive time period (7 years). Crime statistics were taken from the Greek Police. Repeated measures analyses of variance were performed to reveal potential differences in criminality for the years 2008, 2010, 2012 and 2014. There was a significant increase in global criminality rate per 100,000 residents (Wilks' Lambda=0.32, F (3,11)=7.93, p=0.004). There was a significant increase in illegal gun possession (Wilks' Lambda=0.16, F (3,11)=18.68, p=0.001), fraud (Wilks' Lambda=0.10, F (3,11)=32.35, p=0.001), extortion (Wilks' Lambda=0.38, F (3,11)=4.45, p=0.040), and beggary (Wilks' Lambda=0.33, F (3,11)=6.22, p=0.014). A reversed U shape was found for homicides, thefts and robberies, with rates peaking in 2010 and 2012 before dropping off in 2014. Narcotics and sexual exploitation crime rates remained unchanged. Surprisingly, the incidence of rape decreased (Wilks' Lambda=0.42, F (3,11)=5.14, p=0.018). Our results are in agreement with the results of previous broader studies as well as with criminological theories according to which in times of economic stress an increase in both property crimes and violent crimes is expected. As predicted, an increase in financial crime was observed (e.g. fraud and extortions) as well as petty crime related to financial hardship like beggary. Concerns regarding the escalation of white-collar crimes in times of economic downturns that have been raised in the literature warrant further investigation.

  9. Photon energy readings in OSL dosimeter filters: an application to retrospective dose estimation for nuclear medicine workers.

    PubMed

    Villoing, Daphnée; Kitahara, Cari M; Passmore, Christopher; Simon, Steven L; Yoder, R Craig

    2018-06-19

    This work investigates the applicability of using data from personal monitoring dosimeters to assess photon energies to which medical workers were exposed. Such determinations would be important for retrospective assessments of organ doses to be used in occupational radiation epidemiology studies, particularly in the absence of work history or other information regarding the energy of the radiation source. Monthly personal dose equivalents and filter ratios under two different metallic filters contained in the Luxel+® dosimeter were collected from Landauer, Inc. from 19 nuclear medicine (NM) technologists employed by three medical institutions, the institution A only performing traditional NM imaging (primarily using <sup>99m</sup>Tc) and institutions B and C also performing positron emission tomography (PET, using <sup>18</sup>F). Calibration data of the Luxel+® dosimeter for various X-ray spectra were used to establish ranges of filter ratios from 1.1 to 1.6 for <sup>99m</sup>Tc and below 1.1 for <sup>18</sup>F. Median filter ratios were 1.33 (Interquartile range (IQR), 0.15) for institution A, 1.08 (IQR, 0.16) for institution B, and 1.08 (IQR, 0.14) for institution C. The distributions of these filter ratios were statistically-significantly different between the institution A only performing traditional NM imaging and institutions B and C also performing PET imaging. In this proof-of-concept study, filter ratios from personal dosimeters were used to assess differences in photon energies to which NM technologists were exposed. Dosimeters from technologists only performing traditional NM procedures mostly showed Al/Cu filter ratios above 1.2, those likely performing only PET in a particular month had filter ratios below 1.1, and those which showed filter ratios between 1.1 and 1.2 likely came from technologists rotating between traditional NM and PET imaging in the same month. These results suggest that it is possible to distinguish technologists who only worked with higher-energy procedures versus those who only worked with other types of NM procedures. © 2018 IOP Publishing Ltd.

  10. Characterization of Samples Identified as Hepatitis C Virus Genotype 1 without Subtype by Abbott RealTime HCV Genotype II Assay Using the New Abbott HCV Genotype Plus RUO Test.

    PubMed

    Mokhtari, Camelia; Ebel, Anne; Reinhardt, Birgit; Merlin, Sandra; Proust, Stéphanie; Roque-Afonso, Anne-Marie

    2016-02-01

    Hepatitis C virus (HCV) genotyping continues to be relevant for therapeutic strategies. Some samples are reported as genotype 1 (gt 1) without subtype by the Abbott RealTime HCV Genotype II (GT II) test. To characterize such samples further, the Abbott HCV Genotype Plus RUO (Plus) assay, which targets the core region for gt 1a, gt 1b, and gt 6 detection, was evaluated as a reflex test in reference to NS5B or 5'-untranslated region (UTR)/core region sequencing. Of 3,626 routine samples, results of gt 1 without subtype were received for 171 samples (4.7%), accounting for 11.5% of gt 1 specimens. The Plus assay and sequencing were applied to 98 of those samples. NS5B or 5'-UTR/core region sequencing was successful for 91/98 specimens (92.9%). Plus assay and sequencing results were concordant for 87.9% of specimens (80/91 samples). Sequencing confirmed Plus assay results for 82.6%, 85.7%, 100%, and 89.3% of gt 1a, gt 1b, gt 6, and non-gt 1a/1b/6 results, respectively. Notably, 12 gt 6 samples that had been identified previously as gt 1 without subtype were assigned correctly here; for 25/28 samples reported as "not detected" by the Plus assay, sequencing identified the samples as gt 1 with subtypes other than 1a/1b. The genetic variability of HCV continues to present challenges for the current genotyping platforms regardless of the applied methodology. Samples identified by the GT II assay as gt 1 without subtype can be further resolved and reliably characterized by the new Plus assay. Copyright © 2016 Mokhtari et al.

  11. THE RHODOPSIN-TRANSDUCIN COMPLEX HOUSES TWO DISTINCT RHODOPSIN MOLECULES

    PubMed Central

    Jastrzebska, Beata; Ringler, Philipe; Palczewski, Krzysztof; Engel, Andreas

    2013-01-01

    Upon illumination the visual receptor rhodopsin (Rho) transitions to the activated form Rho*, which binds the heterotrimeric G protein, transducin (Gt) causing GDP to GTP exchange and Gt dissociation. Using succinylated concanavalin A (sConA) as a probe, we visualized native Rho dimers solubilized in 1 mM n-dodecyl-β-D-maltoside (DDM) and Rho monomers 5 mM in DDM. By nucleotide depletion and affinity chromatography together with crosslinking and size exclusion chromatography, we trapped and purified nucleotide-free Rho*•Gt and sConA-Rho*•Gt complexes kept in solution by either DDM or lauryl-maltose-neopentyl-glycol (LMNG). The 3-D envelope calculated from projections of negatively stained Rho*•Gt-LMNG complexes accommodated two Rho molecules, one Gt heterotrimer and a detergent belt. Visualization of triple sConA-Rho*•Gt complexes unequivocally demonstrated a pentameric assembly of the Rho*•Gt complex in which the photoactivated Rho* dimer serves as a platform for binding the Gt heterotrimer. Importantly, individual monomers of the Rho* dimer in the heteropentameric complex exhibited different capabilities to be regenerated with either 11-cis or 9-cis-retinal. PMID:23458690

  12. Finite field equation of Yang--Mills theory

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

    Brandt, R.A.; Wing-Chiu, N.; Yeung, W.

    1980-03-01

    We consider the finite local field equation -)(1+1/..cap alpha.. (1+f/sub 4/))g/sup munu/D'Alembertian-partial/sup ..mu../partial/sup ..nu../)A/sup nua/ =-(1+f/sub 3/) g/sup 2/N(A/sup c/..nu..A/sup a/..mu..A/sub ..nu..//sup c/) +xxx+(1-s)/sup 2/M/sup 2/A/sup a/..mu.., introduced by Lowenstein to rigorously describe SU(2) Yang--Mills theory, which is written in terms of normal products. We also consider the operator product expansion A/sup c/..nu..(x+xi) A/sup a/..mu..(x) A/sup b/lambda(x-xi) approx...sigma..M/sup c/ab..nu mu..lambda/sub c/'a'b'..nu..'..mu..'lambda' (xi) N(A/sup nuprimec/'A/sup muprimea/'A/sup lambdaprimeb/')(x), and using asymptotic freedom, we compute the leading behavior of the Wilson coefficients M/sup ...//sub .../(xi) with the help of a computer, and express the normal products in the field equation in terms ofmore » products of the c-number Wilson coefficients and of operator products like A/sup c/..nu..(x+xi) A/sup a/..mu..(x) A/sup b/lambda(x-xi) at separated points. Our result is -)(1+(1/..cap alpha..)(1+f/sub 4/))g/sup munu/D'Alembertian-partial/sup ..mu../partial/sup ..nu../)A/sup nua/ =-(1+f/sub 3/) g/sup 2/lim/sub xiarrow-right0/) (lnxi)/sup -0.28/2b/(A/sup c/..nu.. (x+xi) A/sup a/..mu..(x) A/sub ..nu..//sup c/(x-xi) +epsilon/sup a/bcA/sup muc/(x+xi) partial/sup ..nu../A/sup b//sub ..nu../(x)+xxx) +xxx)+(1-s)/sup 2/M/sup 2/A/sup a/..mu.., where ..beta.. (g) =-bg/sup 3/, and so (lnxi)/sup -0.28/2b/ is the leading behavior of the c-number coefficient multiplying the operator products in the field equation.« less

  13. Bacteriophage lambda: early pioneer and still relevant

    PubMed Central

    Casjens, Sherwood R.; Hendrix, Roger W.

    2015-01-01

    Molecular genetic research on bacteriophage lambda carried out during its golden age from the mid 1950's to mid 1980's was critically important in the attainment of our current understanding of the sophisticated and complex mechanisms by which the expression of genes is controlled, of DNA virus assembly and of the molecular nature of lysogeny. The development of molecular cloning techniques, ironically instigated largely by phage lambda researchers, allowed many phage workers to switch their efforts to other biological systems. Nonetheless, since that time the ongoing study of lambda and its relatives have continued to give important new insights. In this review we give some relevant early history and describe recent developments in understanding the molecular biology of lambda's life cycle. PMID:25742714

  14. Increased expression of interleukin-6 (IL-6) gene transcript in relation to IL-6 promoter hypomethylation in gingival tissue from patients with chronic periodontitis.

    PubMed

    Kobayashi, Tetsuo; Ishida, Kohei; Yoshie, Hiromasa

    2016-09-01

    DNA methylation of the cytokine genes may play a role in the pathogenesis of periodontitis. The aim of this study is to evaluate whether the alteration of interleukin-6 (IL-6) gene promoter methylation in the gingival tissue (GT) and peripheral blood (PB) is unique to chronic periodontitis (CP). DNA isolated from the GT and PB of 25 patients with (CP) and 20 healthy controls (H) was modified with sodium bisulfite and analyzed for IL-6 promoter methylation with direct sequencing. The levels of IL-6 mRNA and serum IL-6 protein were evaluated by a quantitative reverse transcription polymerase chain reaction and an enzyme-linked immunosorbent assay. The CP group showed that the overall methylation rates of IL-6 promoter that contained 19 cytosine-guanine dinucleotide (CpG) motifs were significantly decreased in GT in comparison to PB (p<0.001), which was significantly negatively correlated with the probing depth (p=0.003). The GT and PB of the H group displayed similar overall methylation rates. No significant difference was observed in the methylation rates at each CpG in GT in comparison to the PB in both groups. The levels of IL-6 mRNA in the GT and PB and serum IL-6 of the two groups were comparable. The ratio of IL-6 mRNA in the GT relative to the PB was significantly higher in the CP group than in the H group (p=0.03). The increased expression of IL-6 gene transcription may be related to IL-6 promoter hypomethylation in the GT from CP patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Polyphenols in brewed green tea inhibit prostate tumor xenograft growth by localizing to the tumor and decreasing oxidative stress and angiogenesis

    PubMed Central

    Henning, Susanne M.; Wang, Piwen; Said, Jonathan; Magyar, Clara; Castor, Brandon; Doan, Ngan; Tosity, Carmen; Moro, Aune; Gao, Kun; Li, Luyi; Heber, David

    2011-01-01

    It has been demonstrated in various animal models that the oral administration of green tea (GT) extracts in drinking water can inhibit tumor growth, but the effects of brewed GT on factors promoting tumor growth, including oxidant damage of DNA and protein, angiogenesis, and DNA methylation, have not been tested in an animal model. To explore these potential mechanisms, brewed GT was administered instead of drinking water to male severe combined immunodeficiency (SCID) mice with androgen-dependent human LAPC4 prostate cancer cell subcutaneous xenografts. Tumor volume was decreased significantly in mice consuming GT, and tumor size was significantly correlated with GT polyphenol (GTP) content in tumor tissue. There was a significant reduction in hypoxia-inducible factor 1-alpha and vascular endothelial growth factor protein expression. GT consumption significantly reduced oxidative DNA and protein damage in tumor tissue as determined by 8-hydroxydeoxyguanosine/deoxyguanosine ratio and protein carbonyl assay, respectively. Methylation is known to inhibit antioxidative enzymes such as glutathione S-transferase pi (GSTp1) to permit reactive oxygen species promotion of tumor growth. GT inhibited tumor 5-cytosine DNA methyltransferase 1 (DNMT1) mRNA and protein expression significantly, which may contribute to the inhibition of tumor growth by reactivation of antioxidative enzymes. This study advances our understanding of tumor growth inhibition by brewed GT in an animal model by demonstrating tissue localization of GTPs in correlation with inhibition of tumor growth. Our results suggest that the inhibition of tumor growth is due to GTP-mediated inhibition of oxidative stress and angiogenesis in the LAPC4 xenograft prostate tumor in SCID mice. PMID:22405694

  16. Persistent Genital Tract HIV-1 RNA Shedding After Change in Treatment Regimens in Antiretroviral-Experienced Women with Detectable Plasma Viral Load

    PubMed Central

    DeLong, Allison K.; Kantor, Rami; Chapman, Stacey; Ingersoll, Jessica; Kurpewski, Jaclynn; De Pasquale, Maria Pia; D'Aquila, Richard; Caliendo, Angela M.; Cu-Uvin, Susan

    2013-01-01

    Abstract Objective To longitudinally assess the association between plasma viral load (PVL) and genital tract human immunodeficiency virus (GT HIV) RNA among HIV-1 infected women changing highly active antiretroviral therapy (HAART) because of detectable PVL on current treatment. Methods Women were eligible for the study if they had detectable PVL (defined as two consecutive samples with PVL>1000 copies/mL) and intended to change their current HAART regimen at the time of enrollment. Paired plasma and GT HIV-1 RNA were measured prospectively over 3 years. Longitudinal analyses examined rates of GT HIV-1 RNA shedding and the association with PVL. Results Sixteen women were followed for a median of 11 visits contributing a total of 205 study visits. At study enrollment, all had detectable PVL and 69% had detectable GT HIV-1 RNA. Half of the women changed to a new HAART regimen with ≥3 active antiretroviral drugs. The probability of having detectable PVL ≥30 days after changing HAART was 0.56 (95% CI: 0.37 to 0.74). Fourteen women (88%) had detectable PVL on a follow-up visit ≥30 or 60 days after changing HAART; and 12 women (75%) had detectable GT HIV-1 RNA on a follow-up visit ≥30 or 60 days after changing HAART. When PVL was undetectable, GT shedding occurred at 11% of visits, and when PVL was detectable, GT shedding occurred at 47% of visits. Conclusions Some treatment-experienced HIV-infected women continue to have detectable virus in both the plasma and GT following a change in HAART, highlighting the difficulty of viral suppression in this patient population. PMID:23531097

  17. Photoregeneration of bovine rhodopsin from its signaling state.

    PubMed

    Arnis, S; Hofmann, K P

    1995-07-25

    In rhodopsin, 11-cis-retinal is bound by a protonated Schiff base and acts as a strong antagonist, which holds the receptor in its inactive ground state conformation. Light induces cis-/trans-retinal isomerization and a sequence of thermal transitions through intermediates. The active conformation that catalyzes GDP/GTP exchange in the G-protein (Gt) is generated from the metarhodopsin II intermediate (MII) and mediated by Schiff base proton translocation and proton uptake from the aqueous phase. In the stable nucleotide-free MII-Gt complex, any thermal transition of MII into other forms of rhodopsin is blocked. We have now studied how Gt affects flash-induced photochemical conversions of MII. Difference spectra from measured absorption changes show that MII photolyzes through two parallel pathways, with fast (1 ms) and slow (50 ms) kinetics (12 degrees C, pH 6). The slow pathway regenerates rhodopsin (9- or 11-cis) via Schiff base reprotonation and proton release. We infer a cis-isomerized early photoproduct (reverted meta, RM) preceding these thermal transitions. When MII is photolyzed in the MII-Gt complex, the slow absorption change is abolished, indicating that Gt blocks the completion of the regeneration process. This is due to the formation of a stable RM-Gt complex, as shown by successive photolysis of MII, RM, and ground state rhodopsin, and the application of GTP gamma S at different stages. The complex dissociates with GTP gamma S, and rhodopsin relaxes to the ground state. The results indicate that cis-retinal and Gt can bind to the receptor at the same time. We discuss the result that the protonations in the meta II state uncouple retinal geometry from Gt interaction.

  18. Characterization of recombinant amylopullulanase (gt-apu) and truncated amylopullulanase (gt-apuT) of the extreme thermophile Geobacillus thermoleovorans NP33 and their action in starch saccharification.

    PubMed

    Nisha, M; Satyanarayana, T

    2013-07-01

    A gene encoding amylopullulanase (gt-apu) of the extremely thermophilic Geobacillus thermoleovorans NP33 was cloned and expressed in Escherichia coli. The gene has an open reading frame of 4,965 bp that encodes a protein of 1,655 amino acids with molecular mass of 182 kDa. The six conserved regions, characteristic of GH13 family, have been detected in gt-apu. The recombinant enzyme has only one active site for α-amylase and pullulanase activities based on the enzyme kinetic analyses in a system that contains starch as well as pullulan as competing substrates and response to inhibitors. The end-product analysis confirmed that this is an endoacting enzyme. The specific enzyme activities for α-amylase and pullulanase of the truncated amylopullulanase (gt-apuT) are higher than gt-apu. Both enzymes exhibited similar temperature (60 °C) and pH (7.0) optima, although gt-apuT possessed a higher thermostability than gt-apu. The overall catalytic efficiency (K(cat)/K(m)) of gt-apuT is greater than that of gt-apu, with almost similar substrate specificities. The C-terminal region of gt-apu appeared to be non-essential, and furthermore, it negatively affects the substrate binding and stability of the enzyme.

  19. Identification of vimentin- and elastin-like transcripts specifically expressed in developing notochord of Atlantic salmon (Salmo salar L.).

    PubMed

    Sagstad, Anita; Grotmol, Sindre; Kryvi, Harald; Krossøy, Christel; Totland, Geir K; Malde, Ketil; Wang, Shou; Hansen, Tom; Wargelius, Anna

    2011-11-01

    The notochord functions as the midline structural element of all vertebrate embryos, and allows movement and growth at early developmental stages. Moreover, during embryonic development, notochord cells produce secreted factors that provide positional and fate information to a broad variety of cells within adjacent tissues, for instance those of the vertebrae, central nervous system and somites. Due to the large size of the embryo, the salmon notochord is useful to study as a model for exploring notochord development. To investigate factors that might be involved in notochord development, a normalized cDNA library was constructed from a mix of notochords from ∼500 to ∼800 day°. From the 1968 Sanger-sequenced transcripts, 22 genes were identified to be predominantly expressed in the notochord compared to other organs of salmon. Twelve of these genes were found to show expressional regulation around mineralization of the notochord sheath; 11 genes were up-regulated and one gene was down-regulated. Two genes were found to be specifically expressed in the notochord; these genes showed similarity to vimentin (acc. no GT297094) and elastin (acc. no GT297478). In-situ results showed that the vimentin- like transcript was expressed in both chordocytes and chordoblasts, whereas the elastin- like transcript was uniquely expressed in the chordoblasts lining the notochordal sheath. In salmon aquaculture, vertebral deformities are a common problem, and some malformations have been linked to the notochord. The expression of identified transcripts provides further insight into processes taking place in the developing notochord, prior to and during the early mineralization period.

  20. [In vitro anti-angiogenic action of lambda-carrageenan oligosaccharides].

    PubMed

    Chen, Hai-Min; Yan, Xiao-Jun; Wang, Feng; Lin, Jing; Xu, Wei-Feng

    2007-06-01

    This study was designed to evaluate the inhibition effect of lambda-carrageenan oligosaccharides on neovascularization in vitro by chick chorioallantoic membrane (CAM) model and human umbilical vein endothelial cell ( HUVEC). lambda-Carrageenan oligosaccharides caused a dose-dependent decrease of the vascular density of CAM, and adversely affected capillary plexus formation. At a high concentration of 1 mg x mL(-1), this compound inhibited the endothelial cell proliferation, while low concentration of lambda-carrageenan oligosaccharides (< 250 microg x mL(-1)) affected the cell survival slightly (> 95%). Different cytotoxic sensitivity of lambda-carrageenan oligosaccharides in three kinds of cells was observed, of which HUVEC is the most sensitive to this oligosaccharides. The inhibitory action of lambda-carrageenan oligosaccharides on the endothelial cell invasion and migration was also observed at relatively low concentration (150 - 300 microg x mL(-1)) through down-regulation of intracellular matrix metalloproteinases-2 (MMP-2) expression on endothelial cells. Current observations demonstrated that lambda-carrageenan oligosaccharides are potential angiogenesis inhibitor with combined effects of inhibiting invasion, migration and proliferation.

  1. Expression levels of the PiT-2 receptor explain, in part, the gestational age-dependent alterations in transduction efficiency after in utero retroviral-mediated gene transfer

    PubMed Central

    Ozturk, Ferhat; Park, Paul J.; Tellez, Joseph; Colletti, Evan; Eiden, Maribeth V.; Almeida-Porada, Graça; Porada, Christopher D.

    2014-01-01

    Background A fundamental obstacle to using retroviral-mediated gene transfer (GT) to treat human diseases is the relatively low transduction levels that have been achieved in clinically relevant human cells. We previously showed that performing GT in utero overcomes this obstacle and results in significant levels of transduction within multiple fetal organs, with different tissues exhibiting optimal transduction at different developmental stages. We undertook the present study aiming to elucidate the mechanism for this age-dependent transduction, testing the two factors that we hypothesized could be responsible: (i) the proliferative status of the tissue at the time of GT and (ii) the expression level of the amphotropic PiT-2 receptor. Methods Immunofluorescence was performed on tissues from sheep of varying developmental stages to assess the proliferative status of the predominant cells within each organ as a function of age. After developing an enzyme-linked immunosorbent assay (ELISA) and a quantitative reverse transcription chain reaction (qRT-PCR) assay, we then quantified PiT-2 expression at the protein and mRNA levels, respectively. Results The results obtained indicate that the proliferative status of organs at the time of fetal GT is not the major determinant governing transduction efficiency. By contrast, our ELISA and qRT-PCR analyses demonstrated that PiT-2 mRNA and protein levels vary with gestational age, correlating with the observed differences in transduction efficiency. Conclusions The findings of the present study explain the age-related differences that we previously observed in transduction efficiency after in utero GT. They also suggest it may be possible to achieve relatively selective GT to specific tissues by performing in utero GT when levels of PiT-2 are maximal in the desired target organ. PMID:22262359

  2. Stability of monomeric Cro variants: Isoenergetic transformation of a type I' to a type II' beta-hairpin by single amino acid replacements.

    PubMed

    Mollah, A K M M; Stennis, Rhonda L; Mossing, Michael C

    2003-05-01

    The thermodynamic stabilities of three monomeric variants of the bacteriophage lambda Cro repressor that differ only in the sequence of two amino acids at the apex of an engineered beta-hairpin have been determined. The sequences of the turns are EVK-XX-EVK, where the two central residues are DG, GG, and GT, respectively. Standard-state unfolding free energies, determined from circular dichroism measurements as a function of urea concentration, range from 2.4 to 2.7 kcal/mole, while those determined from guanidine hydrochloride range from 2.8 to 3.3 kcal/mole for the three proteins. Thermal denaturation yields van't Hoff unfolding enthalpies of 36 to 40 kcal /mole at midpoint temperatures in the range of 53 to 58 degrees C. Extrapolation of the thermal denaturation free energies with heat capacities of 400 to 600 cal/mole deg gives good agreement with the parameters determined in denaturant titrations. As predicted from statistical surveys of amino acid replacements in beta-hairpins, energetic barriers to transformation from a type I' turn (DG) to a type II' turn (GT) can be quite small.

  3. TauG-guidance of transients in expressive musical performance.

    PubMed

    Schogler, Benjaman; Pepping, Gert-Jan; Lee, David N

    2008-08-01

    The sounds in expressive musical performance, and the movements that produce them, offer insight into temporal patterns in the brain that generate expression. To gain understanding of these brain patterns, we analyzed two types of transient sounds, and the movements that produced them, during a vocal duet and a bass solo. The transient sounds studied were inter-tone f (0)(t)-glides (the continuous change in fundamental frequency, f (0)(t), when gliding from one tone to the next), and attack intensity-glides (the continuous rise in sound intensity when attacking, or initiating, a tone). The temporal patterns of the inter-tone f (0)(t)-glides and attack intensity-glides, and of the movements producing them, all conformed to the mathematical function, tau (G)(t) (called tauG), predicted by General Tau Theory, and assumed to be generated in the brain. The values of the parameters of the tau (G)(t) function were modulated by the performers when they modulated musical expression. Thus the tau (G)(t) function appears to be a fundamental of brain activity entailed in the generation of expressive temporal patterns of movement and sound.

  4. Measurements of the branching fractions for B{sub (s)}{yields}D{sub (s)}{pi}{pi}{pi} and {Lambda}{sub b}{sup 0}{yields}{Lambda}{sub c}{sup +}{pi}{pi}{pi}

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

    Aaij, R.; Bauer, Th.; Beuzekom, M. van

    Branching fractions of the decays H{sub b}{yields}H{sub c}{pi}{sup -}{pi}{sup +}{pi}{sup -} relative to H{sub b}{yields}H{sub c}{pi}{sup -} are presented, where H{sub b} (H{sub c}) represents B{sup 0} (D{sup +}), B{sup -} (D{sup 0}), B{sub s}{sup 0} (D{sub s}{sup +}), and {Lambda}{sub b}{sup 0} ({Lambda}{sub c}{sup +}). The measurements are performed with the LHCb detector using 35 pb{sup -1} of data collected at {radical}(s)=7 TeV. The ratios of branching fractions are measured to be [B(B{sup 0}{yields}D{sup +}{pi}{sup -}{pi}{sup +}{pi}{sup -})]/[B(B{sup 0}{yields}D{sup +}{pi}{sup -})]=2.38{+-}0.11{+-}0.21, [B(B{sup -}{yields}D{sup 0}{pi}{sup -}{pi}{sup +}{pi}{sup -})]/[B(B{sup -}{yields}D{sup 0}{pi}{sup -})]= 1.27{+-}0.06{+-}0.11, [B(B{sub s}{sup 0}{yields}D{sub s}{sup +}{pi}{sup -}{pi}{sup +}{pi}{sup -})]/[B(B{submore » s}{sup 0}{yields}D{sub s}{sup +}{pi}{sup -})]=2.01{+-}0.37{+-}0.20, [B({Lambda}{sub b}{sup 0}{yields}{Lambda}{sub c}{sup +}{pi}{sup -} {pi}{sup +}{pi}{sup -})]/[B({Lambda}{sub b}{sup 0}{yields}{Lambda}{sub c}{sup +}{pi}{sup -})]=1.43{+-}0.16{+-}0.13 We also report measurements of partial decay rates of these decays to excited charm hadrons. These results are of comparable or higher precision than existing measurements.« less

  5. Simultaneous display of two large proteins on the head and tail of bacteriophage lambda.

    PubMed

    Pavoni, Emiliano; Vaccaro, Paola; D'Alessio, Valeria; De Santis, Rita; Minenkova, Olga

    2013-09-30

    Consistent progress in the development of bacteriophage lambda display platform as an alternative to filamentous phage display system was achieved in the recent years. The lambda phage has been engineered to display efficiently multiple copies of peptides or even large protein domains providing a powerful tool for screening libraries of peptides, proteins and cDNA. In the present work we describe an original method for dual display of large proteins on the surface of lambda particles. An anti-CEA single-chain antibody fragment and green fluorescent protein or alkaline phosphatase were simultaneously displayed by engineering both gpD and gpV lambda proteins. Here we show that such modified phage particles can be used for the detection of target molecules in vitro and in vivo. Dual expression of functional moieties on the surface of the lambda phage might open the way to generation of a new class of diagnostic and therapeutic targeted nanoparticles.

  6. Measurement of the Lambdab0 lifetime in Lambdab0 --> Lambdac+pi- decays in pp collisions at square root of s = 1.96 TeV.

    PubMed

    Aaltonen, T; Adelman, J; Alvarez González, B; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Apollinari, G; Apresyan, A; Arisawa, T; Artikov, A; Asaadi, J; Ashmanskas, W; Attal, A; Aurisano, A; Azfar, F; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Barria, P; Bartos, P; Bauer, G; Beauchemin, P-H; Bedeschi, F; Beecher, D; Behari, S; Bellettini, G; Bellinger, J; Benjamin, D; Beretvas, A; Bhatti, A; Binkley, M; Bisello, D; Bizjak, I; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Bridgeman, A; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Byrum, K L; Cabrera, S; Calancha, C; Camarda, S; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carls, B; Carlsmith, D; Carosi, R; Carrillo, S; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavaliere, V; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, K; Chokheli, D; Chou, J P; Chung, K; Chung, W H; Chung, Y S; Chwalek, T; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Compostella, G; Convery, M E; Conway, J; Corbo, M; Cordelli, M; Cox, C A; Cox, D J; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; Dagenhart, D; Datta, M; Davies, T; de Barbaro, P; De Cecco, S; Deisher, A; De Lorenzo, G; Dell'Orso, M; Deluca, C; Demortier, L; Deng, J; Deninno, M; d'Errico, M; Di Canto, A; di Giovanni, G P; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Donati, S; Dong, P; Dorigo, T; Dube, S; Ebina, K; Elagin, A; Erbacher, R; Errede, D; Errede, S; Ershaidat, N; Eusebi, R; Fang, H C; Farrington, S; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Ferrazza, C; Field, R; Flanagan, G; Forrest, R; Frank, M J; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garberson, F; Garcia, J E; Garfinkel, A F; Garosi, P; Gerberich, H; Gerdes, D; Gessler, A; Giagu, S; Giakoumopoulou, V; Giannetti, P; Gibson, K; Gimmell, J L; Ginsburg, C M; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Grinstein, S; Grosso-Pilcher, C; Group, R C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, S R; Halkiadakis, E; Han, B-Y; Han, J Y; Happacher, F; Hara, K; Hare, D; Hare, M; Harr, R F; Hartz, M; Hatakeyama, K; Hays, C; Heck, M; Heinrich, J; Herndon, M; Heuser, J; Hewamanage, S; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Hou, S; Houlden, M; Hsu, S-C; Hughes, R E; Hurwitz, M; Husemann, U; Hussein, M; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ivanov, A; James, E; Jang, D; Jayatilaka, B; Jeon, E J; Jha, M K; Jindariani, S; Johnson, W; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Kar, D; Karchin, P E; Kato, Y; Kephart, R; Ketchum, W; Keung, J; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, H W; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kreps, M; Kroll, J; Krop, D; Krumnack, N; Kruse, M; Krutelyov, V; Kuhr, T; Kulkarni, N P; Kurata, M; Kwang, S; Laasanen, A T; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; LeCompte, T; Lee, E; Lee, H S; Lee, J S; Lee, S W; Leone, S; Lewis, J D; Lin, C-J; Linacre, J; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, C; Liu, T; Lockyer, N S; Loginov, A; Lovas, L; Lucchesi, D; Lueck, J; Lujan, P; Lukens, P; Lungu, G; Lys, J; Lysak, R; MacQueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maksimovic, P; Malde, S; Malik, S; Manca, G; Manousakis-Katsikakis, A; Margaroli, F; Marino, C; Marino, C P; Martin, A; Martin, M S; Martin, V; Martínez, M; Martínez-Ballarín, R; Mastrandrea, P; Mathis, M; Mattson, M E; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzione, A; Mesropian, C; Miao, T; Mietlicki, D; Miladinovic, N; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyake, H; Moed, S; Moggi, N; Mondragon, M N; Moon, C S; Moore, R; Morello, M J; Morlock, J; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Naganoma, J; Nakamura, K; Nakano, I; Napier, A; Nett, J; Neu, C; Neubauer, M S; Neubauer, S; Nielsen, J; Nodulman, L; Norman, M; Norniella, O; Nurse, E; Oakes, L; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Orava, R; Osterberg, K; Pagan Griso, S; Pagliarone, C; Palencia, E; Papadimitriou, V; Papaikonomou, A; Paramanov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Peiffer, T; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Pianori, E; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Potamianos, K; Poukhov, O; Prokoshin, F; Pronko, A; Ptohos, F; Pueschel, E; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Renton, P; Renz, M; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rodriguez, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Roy, P; Ruiz, A; Russ, J; Rusu, V; Rutherford, B; Saarikko, H; Safonov, A; Sakumoto, W K; Santi, L; Sartori, L; Sato, K; Savoy-Navarro, A; Schlabach, P; Schmidt, A; Schmidt, E E; Schmidt, M A; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sforza, F; Sfyrla, A; Shalhout, S Z; Shears, T; Shepard, P F; Shimojima, M; Shiraishi, S; Shochet, M; Shon, Y; Shreyber, I; Simonenko, A; Sinervo, P; Sisakyan, A; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soha, A; Somalwar, S; Sorin, V; Squillacioti, P; Stanitzki, M; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Strycker, G L; Suh, J S; Sukhanov, A; Suslov, I; Taffard, A; Takashima, R; Takeuchi, Y; Tanaka, R; Tang, J; Tecchio, M; Teng, P K; Thom, J; Thome, J; Thompson, G A; Thomson, E; Tipton, P; Ttito-Guzmán, P; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Totaro, P; Tourneur, S; Trovato, M; Tsai, S-Y; Tu, Y; Turini, N; Ukegawa, F; Uozumi, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Vellidis, C; Vidal, M; Vila, I; Vilar, R; Vogel, M; Volobouev, I; Volpi, G; Wagner, P; Wagner, R G; Wagner, R L; Wagner, W; Wagner-Kuhr, J; Wakisaka, T; Wallny, R; Wang, S M; Warburton, A; Waters, D; Weinberger, M; Weinelt, J; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Wilbur, S; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wolfe, H; Wright, T; Wu, X; Würthwein, F; Yagil, A; Yamamoto, K; Yamaoka, J; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yi, K; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanetti, A; Zeng, Y; Zhang, X; Zheng, Y; Zucchelli, S

    2010-03-12

    We report a measurement of the lifetime of the Lambda(b)(0) baryon in decays to the Lambda(c)(+)pi(-) final state in a sample corresponding to 1.1 fb(-1) collected in pp collisions at square root of s = 1.96 TeV by the CDF II detector at the Tevatron collider. Using a sample of about 3000 fully reconstructed Lambda(b)(0) events we measure tau(Lambda(b)(0)) = 1.401 +/- 0.046(stat) +/- 0.035(syst) ps (corresponding to ctau(Lambda(b)(0)) = 420.1 +/- 13.7(stat) +/- 10.6(syst) microm, where c is the speed of light). The ratio of this result and the world average B(0) lifetime yields tau(Lambda(b)(0))/tau(B(0)) = 0.918 +/- 0.038 (stat) and (syst), in good agreement with recent theoretical predictions.

  7. Measurement of sigma(Lambda(b)0) / sigma(anti-B 0) x B(Lambda0(b) ---> Lambda+(c) pi-) / B(anti-B0 ---> D+ pi-) in p anti-p collisions at S**(1/2) = 1.96-TeV

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

    Abulencia, A.; Acosta, D.; Adelman, Jahred A.

    2006-01-01

    The authors present the first observation of the baryon decay {Lambda}{sub b}{sup 0} {yields} {Lambda}{sub c}{sup +} {pi}{sup -} followed by {Lambda}{sub c}{sup +} {yields} pK{sup -} {pi}{sup +} in 106 pb{sup -1} p{bar p} collisions at {radical}s = 1.96 TeV in the CDF experiment. IN order to reduce systematic error, the measured rate for {Lambda}{sub b}{sup 0} decay is normalized to the kinematically similar meson decay {bar B}{sup 0} {yields} D{sup +}{pi}{sup -} followed by D{sup +} {yields} {pi}{sup +}K{sup -}{pi}{sup +}. They report the ratio of production cross sections ({sigma}) times the ratio of branching fractions ({Beta}) formore » the momentum region integrated above p{sub T} > 6 GeV/c and pseudorapidity range |{eta}| < 1.3: {sigma}(p{bar p} {yields} {Lambda}{sub b}{sup 0}X)/{sigma}(p{bar p} {yields} {bar B}{sup 0} X) x {Beta}({Lambda}{sub b}{sup 0} {yields} {Lambda}{sub c}{sup +}{pi}{sup -})/{Beta}({bar B}{sup 0} {yields} D{sup +}{pi}{sup -}) = 0.82 {+-} 0.08(stat) {+-} 0.11(syst) {+-} 0.22 ({Beta}({Lambda}{sub c}{sup +} {yields} pK{sup -} {pi}{sup +})).« less

  8. The formation of low-ionization emission in the halo of NGC 891

    NASA Technical Reports Server (NTRS)

    Sokolowski, James; Bland-Hawthorn, Jonathan

    1993-01-01

    Imaging and Spectroscopic study first revealed the presence of a diffuse ionized medium (DIM), having unusual excitation, pervading the lower halo of the edge-on spiral galaxy NGC 891. Emission from this DIM is strongest northeast of the nucleus, at radii between 2 and 8 kpc (hereafter region 1). The (N2)(lambda)6583/H(alpha) and (S2)(lambda) (lambda)6716,6731/H(alpha) ratios increase dramatically with z in region 1, from 0.6 and 0.5 respectively at z is approximately equal to 500 pc to 1.1 and 1.0 at z is approximately equal to 1 kpc, while nondetections of (O1)(lambda)6300 and (O3)(lambda)5007 emission yield upper limits of (O1)(lambda)6300/H(alpha) less than or equal to 0.05 and (O3)(lambda)5007/H(alpha) less than or equal to 0.15 for z less than 1 kpc. Previous photoionization models, using the radiation field from disk O and B stars, have been successful in reproducing the elevated (N2)(lambda)6583/H(alpha) and (S2)(lambda)(lambda)6716.6731/H(alpha) ratios observed. However, these radiation bounded models also produce significant (O3)(lambda)5007 emission, in conflict with the observed upper limit. Here, we report the results of new, matter bounded models for the photoionization of the DIM in region 1 of NGC 891.

  9. Trps1 activates a network of secreted Wnt inhibitors and transcription factors crucial to vibrissa follicle morphogenesis

    PubMed Central

    Fantauzzo, Katherine A.; Christiano, Angela M.

    2012-01-01

    Mutations in TRPS1 cause trichorhinophalangeal syndrome types I and III, which are characterized by sparse scalp hair in addition to craniofacial and skeletal abnormalities. Trps1 is a vertebrate transcription factor that contains nine zinc-finger domains, including a GATA-type zinc finger through which it binds DNA. Mice in which the GATA domain of Trps1 has been deleted (Trps1Δgt/Δgt) have a reduced number of pelage follicles and lack vibrissae follicles postnatally. To identify the transcriptional targets of Trps1 in the developing vibrissa follicle, we performed microarray hybridization analysis, comparing expression patterns in the whisker pads of wild-type versus Trps1Δgt/Δgt embryos. We identified a number of transcription factors and Wnt inhibitors among transcripts downregulated in the mutant embryos and several extracellular matrix proteins that were upregulated in the mutant samples, and demonstrated that target gene expression levels were altered in vivo in Trps1Δgt/Δgt vibrissae. Unexpectedly, we discovered that Trps1 can directly bind the promoters of its target genes to activate transcription, expanding upon its established role as a transcriptional repressor. Our findings identify Trps1 as a novel regulator of the Wnt signaling pathway and of early hair follicle progenitors in the developing vibrissa follicle. PMID:22115758

  10. Gastrostomy Tube Feeding in Children With Developmental or Acquired Disorders: A Longitudinal Comparison on Healthcare Provision and Eating Outcomes 4 Years After Gastrostomy.

    PubMed

    Backman, Ellen; Karlsson, Ann-Kristin; Sjögreen, Lotta

    2018-03-30

    Studies on long-term feeding and eating outcomes in children requiring gastrostomy tube feeding (GT) are scarce. The aim of this study was to describe children with developmental or acquired disorders receiving GT and to compare longitudinal eating and feeding outcomes. A secondary aim was to explore healthcare provision related to eating and feeding. This retrospective cohort study reviewed medical records of children in 1 administrative region of Sweden with GT placement between 2005 and 2012. Patient demographics, primary diagnoses, age at GT placement, and professional healthcare contacts prior to and after GT placement were recorded and compared. Feeding and eating outcomes were assessed 4 years after GT placement. The medical records of 51 children, 28 boys and 23 girls, were analyzed and grouped according to "acquired" (n = 13) or "developmental" (n = 38) primary diagnoses. At 4 years after GT placement, 67% were still using GT. Only 6 of 37 (16%) children with developmental disorders transferred to eating all orally, as opposed to 10 of 11 (91%) children with acquired disorders. Children with developmental disorders were younger at the time of GT placement and displayed a longer duration of GT activity when compared with children with acquired disorders. This study demonstrates a clear difference between children with developmental or acquired disorders in duration of GT activity and age at GT placement. The study further shows that healthcare provided to children with GT is in some cases multidisciplinary, but primarily focuses on feeding rather than eating. © 2018 American Society for Parenteral and Enteral Nutrition.

  11. Short-Term Exposure to Lambda-Cyhalothrin Negatively Affects the Survival and Memory-Related Characteristics of Worker Bees Apis mellifera.

    PubMed

    Liao, Chun-Hua; He, Xu-Jiang; Wang, Zi-Long; Barron, Andrew B; Zhang, Bo; Zeng, Zhi-Jiang; Wu, Xiao-Bo

    2018-07-01

    Pesticides are considered one of the major contemporary stressors of honey bee health. In this study, the effects of short-term exposure to lambda-cyhalothrin on lifespan, learning, and memory-related characteristics of Apis mellifera were systematically examined. Short-term exposure to lambda-cyhalothrin in worker bees reduced lifespan, affected learning and memory performance, reduced the homing ability, and influenced the expression levels of two learning and memory-related genes of A. mellifera. This research identifies the nature of the sublethal effects of lambda-cyhalothrin on bees and the level of exposure that can be harmful to bee health. This new information will assist in establishing guidelines for the safe use of lambda-cyhalothrin in the field.

  12. The rhodopsin-transducin complex houses two distinct rhodopsin molecules.

    PubMed

    Jastrzebska, Beata; Ringler, Philippe; Palczewski, Krzysztof; Engel, Andreas

    2013-05-01

    Upon illumination the visual receptor rhodopsin (Rho) transitions to the activated form Rho(∗), which binds the heterotrimeric G protein, transducin (Gt) causing GDP to GTP exchange and Gt dissociation. Using succinylated concanavalin A (sConA) as a probe, we visualized native Rho dimers solubilized in 1mM n-dodecyl-β-d-maltoside (DDM) and Rho monomers in 5mM DDM. By nucleotide depletion and affinity chromatography together with crosslinking and size exclusion chromatography, we trapped and purified nucleotide-free Rho(∗)·Gt and sConA-Rho(∗)·Gt complexes kept in solution by either DDM or lauryl-maltose-neopentyl-glycol (LMNG). The 3 D envelope calculated from projections of negatively stained Rho(∗)·Gt-LMNG complexes accommodated two Rho molecules, one Gt heterotrimer and a detergent belt. Visualization of triple sConA-Rho(∗)·Gt complexes unequivocally demonstrated a pentameric assembly of the Rho(∗)·Gt complex in which the photoactivated Rho(∗) dimer serves as a platform for binding the Gt heterotrimer. Importantly, individual monomers of the Rho(∗) dimer in the heteropentameric complex exhibited different capabilities for regeneration with either 11-cis or 9-cis-retinal. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Gene expression analysis and enzyme assay reveal a potential role of the carboxylesterase gene CpCE-1 from Cydia pomonella in detoxification of insecticides.

    PubMed

    Yang, Xue-Qing

    2016-05-01

    Carboxylesterases (CarEs) are responsible for metabolism of xenobiotics including insecticides in insects. Understanding the expression patterns of a such detoxifying gene and effect of insecticides on its enzyme activity are important to clarify the function of this gene relevant to insecticides-detoxifying process, but little information is available in the codling moth Cydia pomonella (L.). In this study, we investigated the expression profiles of CarE gene CpCE-1 at different developmental stages and in different tissues of C. pomonella, as well as the larvae exposed to chlorpyrifos-ethyl and lambda-cyhalothrin by using absolute real-time quantitative PCR (absolute RT-qPCR). Results indicated that CpCE-1 expression was significantly altered during C. pomonella development stages, and this expression differed between sexes, with a higher transcript in females than males. Meanwhile, CpCE-1 is overexpressed in cuticle, midgut and head than silk gland, fat body and Malpighian tubules. Exposure of third instar larvae to a non-lethal dosage of chlorpyrifos-ethyl and lambda-cyhalothrin resulted in induction of CpCE-1 transcript. The total carboxylesterase enzyme activity was inhibited by chlorpyrifos-ethyl in vivo; in contrast, the activity of Escherichia coli produced recombinant CpCE-1 was significantly inhibited by both lambda-cyhalothrin and chlorpyrifos-ethyl in vitro. These results suggested that CpCE-1 in C. pomonella is potentially involved in the development and in detoxification of chlorpyrifos-ethyl and lambda-cyhalothrin.

  14. [Excitation transfer between high-lying states in K2 in collisions with ground state K and H2 molecules].

    PubMed

    Shen, Xiao-Yan; Liu, Jing; Dai, Kang; Shen, Yi-Fan

    2010-02-01

    Pure potassium vapor or K-H2 mixture was irradiated in a glass fluorescence cell with pulses of 710 nm radiation from an OPO laser, populating K2 (1lambda(g)) state by two-photon absorption. Cross sections for 1lambda(g)-3lambda(g) transfer in K2 were determined using methods of molecular fluorescence. During the experiments with pure K vapor, the cell temperature was varied between 553 and 603 K. The K number density was determined spectroscopically by the white-light absorption measurement in the blue wing of the self-broadened resonance D2 line. The resulting fluorescence included a direct component emitted in the decay of the optically excitation and a sensitized component arising from the collisionally populated state. The decay signal of time-resolved fluorescence from1lambda(g) -->1 1sigma(u)+ transition was monitored. It was seen that just after the laser pulse the fluorescence of the photoexcited level decreased exponentially. The effective lifetimes of the 1lambda(g) state can be resolved. The plot of reciprocal of effective lifetimes of the 1lambda(g) state against K densities yielded the slope that indicated the total cross section for deactivation and the intercept that provided the radiative lifetime of the state. The radiative lifetime (20 +/- 2) ns was obtained. The cross section for deactivation of the K2(1lambda(g)) molecules by collisions with K is (2.5 +/- 0.3) x 10(-14) cm2. The time-resolved intensities of the K23lambda(g) --> 1 3sigma(u)+ (484 nm) line were measured. The radiative lifetime (16.0 +/- 3.2) ns and the total cross section (2.5 +/- 0.6) x 10(-14) cm2 for deactivation of the K2 (3lambda(g)) state can also be determined through the analogous procedure. The time-integrated intensities of 1lambda(g) --> 1 1sigma(u)+ and 3lambda(g) --> 1 3sigma(u)+ transitions were measured. The cross section (1.1 +/- 0.3) x10(-14) cm2 was obtained for K2 (1lambda(g))+ K --> K2 (3lambda(g)) + K collisions. During the experiments with K-H2 mixture, the cell temperature was kept constant at 553 K. The H2 pressure was varied between 40 and 400 Pa. The effects of K2-K collisions could not be neglected. These effects were subtracted out using the results of the pure K experiments. The cross section (2.7 +/- 1.1) x 10(-15) cm2 was obtained for K2 (1lambda(g)) + H2 --> K2 (3lambda(g))+H2 collisions. The cross section is (6.8 +/- 2.7) x 10(-15) cm2 for K2 (3lambda(g)) + H2 --> states out of K2 (3lambda(g)) + H2 collisions.

  15. Depolymerized products of lambda-carrageenan as a potent angiogenesis inhibitor.

    PubMed

    Chen, Haimin; Yan, Xiaojun; Lin, Jing; Wang, Feng; Xu, Weifeng

    2007-08-22

    Since angiogenesis is involved in initiating and promoting several diseases such as cancer and cardiovascular events, this study was designed to evaluate the anti-angiogenesis of low-molecular-weight (LMW), highly sulfated lambda-carrageenan oligosaccharides (lambda-CO) obtained by carrageenan depolymerization, by CAM (chick chorioallantoic membrane) model and human umbilical vein endothelial cells (HUVECs). Significant inhibition of vessel growth was observed at 200 microg/pellet. A histochemistry assay also revealed a decrease of capillary plexus and connective tissue in lambda-CO treated samples. lambda-CO inhibited the viability of cells at the high concentration of 1 mg/mL, whereas it affected the cell survival slightly (>95%) at a low concentration (<250 microg/mL), and HUVEC is the most sensitive to lambda-CO among three kinds of cells. Furthermore, the inhibitory action of lambda-CO was also observed in the endothelial cell invasion and migration at relatively low concentration (150-300 microg/mL), through down-regulation of intracellular matrix metalloproteinases (MMP-2) expression on endothelial cells. Taken together, these findings demonstrate that lambda-CO is a potential angiogenesis inhibitor with combined effects of inhibiting invasion, migration, and proliferation.

  16. Golgi retention of a trans-Golgi membrane protein, galactosyltransferase, requires cysteine and histidine residues within the membrane-anchoring domain.

    PubMed

    Aoki, D; Lee, N; Yamaguchi, N; Dubois, C; Fukuda, M N

    1992-05-15

    Galactosyltransferase (GT; UDPgalactose:beta-D-N-acetylglucosaminide beta-1,4-galactosyltransferase, EC 2.4.1.22) is a type II membrane-anchored protein composed of a short N-terminal cytoplasmic tail, a signal/membrane-anchoring domain, and a stem region followed by a large catalytic domain including the C terminus. To identify the peptide segment and key amino acid residues that are critical for Golgi localization of GT, the expression vector pGT-hCG was designed to encode the entire GT molecule fused to the C-terminal region of human chorionic gonadotropin alpha subunit (hCG alpha) as a reporter. COS-1 cells transfected with pGT-hCG expressed the chimera in the Golgi region, as detected by immunofluorescence microscopy using anti-hCG antibodies. Two deletion mutants, delta tail and delta stem, which are lacking most of the N-terminal cytoplasmic tail or 10 amino acids immediately after the membrane-anchoring domain, were localized in the Golgi. Replacement mutations of the membrane-anchoring domain of GT showed that the second quarter of the transmembrane domain or Cys29-Ala30-Leu31-His32-Leu33 is necessary for GT to be retained in the Golgi. Furthermore, the point mutants Cys29----Ser29 and His32----Leu32 were partially transported to the plasma membrane, whereas an Ala30-Leu31----Phe30-Gly31 mutant was localized in the Golgi. Finally, a double mutant, Cys29/His32----Ser29/Leu32, was found to be transported efficiently to the plasma membrane. The signal-anchoring domain of the transferrin receptor, a type II plasma membrane protein, was then replaced by portions of the GT transmembrane domain. Although the Cys-Xaa-Xaa-His sequence by itself cannot retain the transferrin receptor in the Golgi, the cytoplasmic half of the transmembrane domain of GT was partially capable of retaining the transferrin receptor in the Golgi. These results suggest that the cytoplasmic (or N-terminal) half of the transmembrane domain of GT contributes to the Golgi retention signal and that particularly Cys29 and His32 in this region are critical for GT to be retained in the Golgi.

  17. Golgi retention of a trans-Golgi membrane protein, galactosyltransferase, requires cysteine and histidine residues within the membrane-anchoring domain.

    PubMed Central

    Aoki, D; Lee, N; Yamaguchi, N; Dubois, C; Fukuda, M N

    1992-01-01

    Galactosyltransferase (GT; UDPgalactose:beta-D-N-acetylglucosaminide beta-1,4-galactosyltransferase, EC 2.4.1.22) is a type II membrane-anchored protein composed of a short N-terminal cytoplasmic tail, a signal/membrane-anchoring domain, and a stem region followed by a large catalytic domain including the C terminus. To identify the peptide segment and key amino acid residues that are critical for Golgi localization of GT, the expression vector pGT-hCG was designed to encode the entire GT molecule fused to the C-terminal region of human chorionic gonadotropin alpha subunit (hCG alpha) as a reporter. COS-1 cells transfected with pGT-hCG expressed the chimera in the Golgi region, as detected by immunofluorescence microscopy using anti-hCG antibodies. Two deletion mutants, delta tail and delta stem, which are lacking most of the N-terminal cytoplasmic tail or 10 amino acids immediately after the membrane-anchoring domain, were localized in the Golgi. Replacement mutations of the membrane-anchoring domain of GT showed that the second quarter of the transmembrane domain or Cys29-Ala30-Leu31-His32-Leu33 is necessary for GT to be retained in the Golgi. Furthermore, the point mutants Cys29----Ser29 and His32----Leu32 were partially transported to the plasma membrane, whereas an Ala30-Leu31----Phe30-Gly31 mutant was localized in the Golgi. Finally, a double mutant, Cys29/His32----Ser29/Leu32, was found to be transported efficiently to the plasma membrane. The signal-anchoring domain of the transferrin receptor, a type II plasma membrane protein, was then replaced by portions of the GT transmembrane domain. Although the Cys-Xaa-Xaa-His sequence by itself cannot retain the transferrin receptor in the Golgi, the cytoplasmic half of the transmembrane domain of GT was partially capable of retaining the transferrin receptor in the Golgi. These results suggest that the cytoplasmic (or N-terminal) half of the transmembrane domain of GT contributes to the Golgi retention signal and that particularly Cys29 and His32 in this region are critical for GT to be retained in the Golgi. Images PMID:1584766

  18. The anomalous C 4 intensity ratio in symbiotic stars

    NASA Technical Reports Server (NTRS)

    Michalitsianos, A. G.; Kafatos, M.; Fahey, R. P.

    1988-01-01

    The C IV lambda lambda 1548.2,1550.8 resonance doublet in a symbiotic stars was shown to exhibit anomalous line intensity ratios in which I (lambda 1548.2)/I(lambda 1550.8) less than 1, or less than the optically-thick limit of unity. The R Aquarii-central HII region and RX Puppis exhibit this phenomena. The I(lambda 1548.2)/I(lambda 1550.8) ratio in RX Puppis is found to vary inversely with the total C IV line intensity, and with the FES-visual light, as the object declined over a 5 yr period following a brightening in UV and optical emission which peaked in 1982. This doublet intensity behavior could be explained by a wind which has a narrow velocity range of 600 approx. less than sup v wind approx. less than 1000 km/sec, or by the pumping of the Fe II (mul. 45.01) transition a sup 4 F sub 9/2 - y sup 4 H(o) sub 11/2 by C IV lambda 1548.2, which effectively scatters C IV photons into the Fe II spectrum in these objects.

  19. Activity-Based Profiling of a Physiologic Aglycone Library Reveals Sugar Acceptor Promiscuity of Family 1 UDP-Glucosyltransferases from Grape1[W

    PubMed Central

    Bönisch, Friedericke; Frotscher, Johanna; Stanitzek, Sarah; Rühl, Ernst; Wüst, Matthias; Bitz, Oliver; Schwab, Wilfried

    2014-01-01

    Monoterpenols serve various biological functions and accumulate in grape (Vitis vinifera), where a major fraction occurs as nonvolatile glycosides. We have screened the grape genome for sequences with similarity to terpene URIDINE DIPHOSPHATE GLYCOSYLTRANSFERASES (UGTs) from Arabidopsis (Arabidopsis thaliana). A ripening-related expression pattern was shown for three candidates by spatial and temporal expression analyses in five grape cultivars. Transcript accumulation correlated with the production of monoterpenyl β-d-glucosides in grape exocarp during ripening and was low in vegetative tissue. Targeted functional screening of the recombinant UGTs for their biological substrates was performed by activity-based metabolite profiling (ABMP) employing a physiologic library of aglycones built from glycosides isolated from grape. This approach led to the identification of two UDP-glucose:monoterpenol β-d-glucosyltransferases. Whereas VvGT14a glucosylated geraniol, R,S-citronellol, and nerol with similar efficiency, the three allelic forms VvGT15a, VvGT15b, and VvGT15c preferred geraniol over nerol. Kinetic resolution of R,S-citronellol and R,S-linalool was shown for VvGT15a and VvGT14a, respectively. ABMP revealed geraniol as the major biological substrate but also disclosed that these UGTs may add to the production of further glycoconjugates in planta. ABMP of aglycone libraries provides a versatile tool to uncover novel biologically relevant substrates of small-molecule glycosyltransferases that often show broad sugar acceptor promiscuity. PMID:25073706

  20. Formulation of a dry green tea-apple product: study on antioxidant and color stability.

    PubMed

    Lavelli, Vera; Vantaggi, Claudia; Corey, Mark; Kerr, William

    2010-03-01

    A dry apple product enriched with green tea (GT) extract was designed as a novel food to deliver relevant amounts of catechins. The target water activity (a(w)) range between 0.11 and 0.32 was chosen for the GT-fortified apple, since it corresponds to low water mobility and, consequently, maximum stability of dehydrated apples. The GT-fortified product and a control dehydrated apple product were stored in air, at 30 degrees C, and evaluated for color, antioxidant contents (monomeric flavan 3-ols, total procyanidins, ascorbic acid, chlorogenic acid and dihydrochalcones), ferric reducing/antioxidant power (FRAP), and 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl radical (DPPH) scavenging capacity. After 1 mo of storage at the lowest a(w) level (0.11), the GT-fortified product retained 80 and 100% of the initial contents of the monomeric flavan 3-ols and total procyanidins, respectively. With increasing a(w) level to 0.32, the stability of antioxidants slowly decreased. The addition of GT to the apple product increased the FRAP value and the DPPH scavenging capacity by 3.6-fold and 4.6-fold respectively, which remained almost unchanged during storage. The GT-fortified product was similar in color to commercially available dehydrated apples. Results highlighted some advantages of using dehydrated apples as a target for green tea fortification, which deserve further trials to investigate potential applications for fortification of other dehydrated fruits.

  1. Productive infection of Epstein-Barr virus (EBV) in EBV-genome-positive epithelial cell lines (GT38 and GT39) derived from gastric tissues.

    PubMed

    Takasaka, N; Tajima, M; Okinaga, K; Satoh, Y; Hoshikawa, Y; Katsumoto, T; Kurata, T; Sairenji, T

    1998-08-01

    We characterized the expression of Epstein-Barr virus (EBV) on two epithelial cell lines, GT38 and GT39, derived from human gastric tissues. The EBV nuclear antigen (EBNA) was detected in all cells of both cell lines. The EBV immediate-early BZLF 1 protein (ZEBRA), the early antigen diffuse component (EA-D), and one of the EBV envelope proteins (gp350/220) were expressed spontaneously in small proportions in the cells. EBNA 1, EBNA2, latent membrane protein 1, ZEBRA, and EA-D molecules were then observed by Western blotting in the cells. The lytic cycle was enhanced with treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) or n-butyrate. The virus particles were observed in the TPA treated GT38 cells by electron microscopy. Infectious EBV was detected with the transformation of cord blood lymphocytes and also with the induction of early antigen to Raji cells by the supernatants of both cells lines. A major single and minor multiple fused terminal fragments and a ladder of smaller fragments of the EBV genome were detected with a Xhol probe in both cell lines. These epithelial cells lines and viruses will be useful in studying their association with EBV in gastric epithelial cells.

  2. αIIbβ3 variants defined by next-generation sequencing: Predicting variants likely to cause Glanzmann thrombasthenia

    PubMed Central

    Buitrago, Lorena; Rendon, Augusto; Liang, Yupu; Simeoni, Ilenia; Negri, Ana; Filizola, Marta; Ouwehand, Willem H.; Coller, Barry S.; Alessi, Marie-Christine; Ballmaier, Matthias; Bariana, Tadbir; Bellissimo, Daniel; Bertoli, Marta; Bray, Paul; Bury, Loredana; Carrell, Robin; Cattaneo, Marco; Collins, Peter; French, Deborah; Favier, Remi; Freson, Kathleen; Furie, Bruce; Germeshausen, Manuela; Ghevaert, Cedric; Gomez, Keith; Goodeve, Anne; Gresele, Paolo; Guerrero, Jose; Hampshire, Dan J.; Hadinnapola, Charaka; Heemskerk, Johan; Henskens, Yvonne; Hill, Marian; Hogg, Nancy; Johnsen, Jill; Kahr, Walter; Kerr, Ron; Kunishima, Shinji; Laffan, Michael; Natwani, Amit; Neerman-Arbez, Marguerite; Nurden, Paquita; Nurden, Alan; Ormiston, Mark; Othman, Maha; Ouwehand, Willem; Perry, David; Vilk, Shoshana Ravel; Reitsma, Pieter; Rondina, Matthew; Simeoni, Ilenia; Smethurst, Peter; Stephens, Jonathan; Stevenson, William; Szkotak, Artur; Turro, Ernest; Van Geet, Christel; Vries, Minka; Ward, June; Waye, John; Westbury, Sarah; Whiteheart, Sidney; Wilcox, David; Zhang, Bi

    2015-01-01

    Next-generation sequencing is transforming our understanding of human genetic variation but assessing the functional impact of novel variants presents challenges. We analyzed missense variants in the integrin αIIbβ3 receptor subunit genes ITGA2B and ITGB3 identified by whole-exome or -genome sequencing in the ThromboGenomics project, comprising ∼32,000 alleles from 16,108 individuals. We analyzed the results in comparison with 111 missense variants in these genes previously reported as being associated with Glanzmann thrombasthenia (GT), 20 associated with alloimmune thrombocytopenia, and 5 associated with aniso/macrothrombocytopenia. We identified 114 novel missense variants in ITGA2B (affecting ∼11% of the amino acids) and 68 novel missense variants in ITGB3 (affecting ∼9% of the amino acids). Of the variants, 96% had minor allele frequencies (MAF) < 0.1%, indicating their rarity. Based on sequence conservation, MAF, and location on a complete model of αIIbβ3, we selected three novel variants that affect amino acids previously associated with GT for expression in HEK293 cells. αIIb P176H and β3 C547G severely reduced αIIbβ3 expression, whereas αIIb P943A partially reduced αIIbβ3 expression and had no effect on fibrinogen binding. We used receiver operating characteristic curves of combined annotation-dependent depletion, Polyphen 2-HDIV, and sorting intolerant from tolerant to estimate the percentage of novel variants likely to be deleterious. At optimal cut-off values, which had 69–98% sensitivity in detecting GT mutations, between 27% and 71% of the novel αIIb or β3 missense variants were predicted to be deleterious. Our data have implications for understanding the evolutionary pressure on αIIbβ3 and highlight the challenges in predicting the clinical significance of novel missense variants. PMID:25827233

  3. Molecular biology based assessment of green tea effects on oxidative stress and cardiac remodelling in dialysis patients.

    PubMed

    Calo, Lorenzo A; Vertolli, Ugo; Davis, Paul A; Maso, Lucia Dal; Pagnin, Elisa; Ravarotto, Verdiana; Maiolino, Giuseppe; Lupia, Mario; Seccia, Teresa M; Rossi, Gian Paolo

    2014-06-01

    Cardiovascular disease, the most common cause for morbidity and mortality in end-stage renal disease (ESRD), has prompted the exploration of multiple approaches to improve outcomes. Cardiovascular risk factors such as oxidative stress (OxSt) and cardiac remodelling are common in ESRD and dialysis patients. Green tea (GT) is well recognized as reducing OxSt. This 6 months study evaluated in 20 ESRD patients under chronic dialysis, the effect of GT treatment (1 g/day as commercially available capsule) on cellular and plasma OxSt and proliferation related markers using a molecular biology approach. Mononuclear cell p22(phox), Haeme Oxygenase (HO)-1 protein expression, and phosphorylated ERK1/2 status were evaluated in dialysis patients at baseline, after 3 and 6 months of GT treatment by Western blot analysis and plasma oxLDL by ELISA. Cardiac remodelling was assessed by echocardiographic left ventricular (LV) mass determination at baseline and at the end of the study. GT treatment reduced p22(phox) and pERK1/2 from baseline while HO-1 increased. At baseline, LV mass correlated with both p22(phox) and oxLDL. GT treatment decreased LV mass from baseline, which correlated with oxLDL. 9 patients had LV hypertrophy at baseline, which, at 6 months, was normalized in 5 and reduced in 3, showing a parallel decrease of p22(phox), pERK1/2, oxLDL and increase of HO-1. Treatment with GT decreased the expression of OxSt-related proteins tightly associated with cardiovascular disease and decreased LV mass. It appears highly likely that the addition of GT can provide a benefit in terms of cardiovascular protection in dialysis patients. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  4. Simultaneous display of two large proteins on the head and tail of bacteriophage lambda

    PubMed Central

    2013-01-01

    Background Consistent progress in the development of bacteriophage lambda display platform as an alternative to filamentous phage display system was achieved in the recent years. The lambda phage has been engineered to display efficiently multiple copies of peptides or even large protein domains providing a powerful tool for screening libraries of peptides, proteins and cDNA. Results In the present work we describe an original method for dual display of large proteins on the surface of lambda particles. An anti-CEA single-chain antibody fragment and green fluorescent protein or alkaline phosphatase were simultaneously displayed by engineering both gpD and gpV lambda proteins. Conclusions Here we show that such modified phage particles can be used for the detection of target molecules in vitro and in vivo. Dual expression of functional moieties on the surface of the lambda phage might open the way to generation of a new class of diagnostic and therapeutic targeted nanoparticles. PMID:24073829

  5. A role for gamma-glutamyl transpeptidase and the amino acid transport system xc- in cystine transport by a human pancreatic duct cell line.

    PubMed Central

    Sweiry, J H; Sastre, J; Viña, J; Elsässer, H P; Mann, G E

    1995-01-01

    1. The roles of the gamma-glutamyl cycle and the anionic amino acid transport system xc- in mediating L-cystine uptake were investigated in cultured human pancreatic duct PaTu 8902 cells. This cell line exhibits morphological features of normal pancreatic duct cells and expresses gamma-glutamyl transpeptidase (gamma-GT, EC 2.3.2.2), an enzyme involved in the metabolism and regulation of intracellular glutathione (GSH). 2. Uptake of L-cystine (10 microM) was linear for up to 10 min, temperature dependent, Na+ independent, saturable (Michaelis-Menten constant (Km), 86 +/- 25 microM; maximal velocity (Vmax), 109 +/- 33 nmol (mg protein)-1 h-1) and reduced by 80-90% by a 50-fold excess concentration of L-glutamate and L-homocysteic acid, but not L-aspartate. These transport properties resemble those described for system xc-, which exchanges cystine for intracellular glutamate. 3. Acivicin, a known inhibitor of gamma-GT, decreased gamma-GT activity from 2.58 +/- 0.96 to 0.97 +/- 0.11 mU (mg protein)-1 and decreased the initial rates of L-cystine and L-glutamine uptake by 41-55%. Anthglutin (1-gamma-L-glutamyl-2-(2-carboxyphenylhyl)hydrazine), a structurally different inhibitor of gamma-GT, also caused a concentration-dependent (0.01-1 mM) decrease in gamma-GT activity and L-cystine uptake. 4. Neither acivicin nor anthglutin inhibited the uptake of L-glutamate, a poor substrate for gamma-GT. 5. In the presence of a 500-fold excess concentration of glutamate, which should abolish entry of cystine via system xc-, the remaining fraction of cystine transport was inhibited by 50% by acivicin, suggesting that transport is, in part, dependent on the activity of gamma-GT. 6. Cystine transport was also 60-80% inhibited by a series of gamma-glutamyl amino acids (5 mM) including gamma-glutamyl-glutamate, gamma-glutamyl-glutamine and gamma-glutamyl-glycine. alpha-Dipeptides inhibited cystine transport by only 6-22%. 7. These findings demonstrate that in human pancreatic duct PaTu 8902 cells, cystine uptake is mediated by system xc- (50-60%) and the gamma-glutamyl cycle. Our results provide the first evidence linking gamma-GT with cystine transport in human epithelial cells and are of relevance in view of the importance of cystine as a sulphur amino acid source for GSH synthesis in cells exposed to oxidative stress. Images Figure 1 PMID:7658371

  6. Molecular cloning of a cDNA encoding the glycoprotein of hen oviduct microsomal signal peptidase.

    PubMed Central

    Newsome, A L; McLean, J W; Lively, M O

    1992-01-01

    Detergent-solubilized hen oviduct signal peptidase has been characterized previously as an apparent complex of a 19 kDa protein and a 23 kDa glycoprotein (GP23) [Baker & Lively (1987) Biochemistry 26, 8561-8567]. A cDNA clone encoding GP23 from a chicken oviduct lambda gt11 cDNA library has now been characterized. The cDNA encodes a protein of 180 amino acid residues with a single site for asparagine-linked glycosylation that has been directly identified by amino acid sequence analysis of a tryptic-digest peptide containing the glycosylated site. Immunoblot analysis reveals cross-reactivity with a dog pancreas protein. Comparison of the deduced amino acid sequence of GP23 with the 22/23 kDa glycoprotein of dog microsomal signal peptidase [Shelness, Kanwar & Blobel (1988) J. Biol. Chem. 263, 17063-17070], one of five proteins associated with this enzyme, reveals that the amino acid sequences are 90% identical. Thus the signal peptidase glycoprotein is as highly conserved as the sequences of cytochromes c and b from these same species and is likely to be found in a similar form in many, if not all, vertebrate species. The data also show conclusively that the dog and avian signal peptidases have at least one protein subunit in common. Images Fig. 1. PMID:1546959

  7. Cebpd Is Essential for Gamma-Tocotrienol Mediated Protection against Radiation-Induced Hematopoietic and Intestinal Injury

    PubMed Central

    Banerjee, Sudip; Shah, Sumit K.; Melnyk, Stepan B.; Hauer-Jensen, Martin

    2018-01-01

    Gamma-tocotrienol (GT3) confers protection against ionizing radiation (IR)-induced injury. However, the molecular targets that underlie the protective functions of GT3 are not yet known. We have reported that mice lacking CCAAT enhancer binding protein delta (Cebpd−/−) display increased mortality to IR due to injury to the hematopoietic and intestinal tissues and that Cebpd protects from IR-induced oxidative stress and cell death. The purpose of this study was to investigate whether Cebpd mediates the radio protective functions of GT3. We found that GT3-treated Cebpd−/− mice showed partial recovery of white blood cells compared to GT3-treated Cebpd+/+ mice at 2 weeks post-IR. GT3-treated Cebpd−/− mice showed an increased loss of intestinal crypt colonies, which correlated with increased expression of inflammatory cytokines and chemokines, increased levels of oxidized glutathione (GSSG), S-nitrosoglutathione (GSNO) and 3-nitrotyrosine (3-NT) after exposure to IR compared to GT3-treated Cebpd+/+ mice. Cebpd is induced by IR as well as a combination of IR and GT3 in the intestine. Studies have shown that granulocyte-colony stimulating factor (G-CSF), mediates the radioprotective functions of GT3. Interestingly, we found that IR alone as well as the combination of IR and GT3 caused robust augmentation of plasma G-CSF in both Cebpd+/+ and Cebpd−/− mice. These results identify a novel role for Cebpd in GT3-mediated protection against IR-induced injury, in part via modulation of IR-induced inflammation and oxidative/nitrosative stress, which is independent of G-CSF. PMID:29642403

  8. A conserved fungal glycosyltransferase facilitates pathogenesis of plants by enabling hyphal growth on solid surfaces

    PubMed Central

    Plummer, Amy; Halsey, Kirstie; Lovegrove, Alison; Hammond-Kosack, Kim

    2017-01-01

    Pathogenic fungi must extend filamentous hyphae across solid surfaces to cause diseases of plants. However, the full inventory of genes which support this is incomplete and many may be currently concealed due to their essentiality for the hyphal growth form. During a random T-DNA mutagenesis screen performed on the pleomorphic wheat (Triticum aestivum) pathogen Zymoseptoria tritici, we acquired a mutant unable to extend hyphae specifically when on solid surfaces. In contrast “yeast-like” growth, and all other growth forms, were unaffected. The inability to extend surface hyphae resulted in a complete loss of virulence on plants. The affected gene encoded a predicted type 2 glycosyltransferase (ZtGT2). Analysis of >800 genomes from taxonomically diverse fungi highlighted a generally widespread, but discontinuous, distribution of ZtGT2 orthologues, and a complete absence of any similar proteins in non-filamentous ascomycete yeasts. Deletion mutants of the ZtGT2 orthologue in the taxonomically un-related fungus Fusarium graminearum were also severely impaired in hyphal growth and non-pathogenic on wheat ears. ZtGT2 expression increased during filamentous growth and electron microscopy on deletion mutants (ΔZtGT2) suggested the protein functions to maintain the outermost surface of the fungal cell wall. Despite this, adhesion to leaf surfaces was unaffected in ΔZtGT2 mutants and global RNAseq-based gene expression profiling highlighted that surface-sensing and protein secretion was also largely unaffected. However, ΔZtGT2 mutants constitutively overexpressed several transmembrane and secreted proteins, including an important LysM-domain chitin-binding virulence effector, Zt3LysM. ZtGT2 likely functions in the synthesis of a currently unknown, potentially minor but widespread, extracellular or outer cell wall polysaccharide which plays a key role in facilitating many interactions between plants and fungi by enabling hyphal growth on solid matrices. PMID:29020037

  9. Differences in Reporting the Ragweed Pollen Season Using Google Trends across 15 Countries.

    PubMed

    Bousquet, Jean; Agache, Ioana; Berger, Uwe; Bergmann, Karl-Christian; Besancenot, Jean-Pierre; Bousquet, Philippe J; Casale, Tom; d'Amato, Gennaro; Kaidashev, Igor; Khaitov, Musa; Mösges, Ralph; Nekam, Kristof; Onorato, Gabrielle L; Plavec, Davor; Sheikh, Aziz; Thibaudon, Michel; Vautard, Robert; Zidarn, Mihaela

    2018-05-09

    Google Trends (GT) searches trends of specific queries in Google, which potentially reflect the real-life epidemiology of allergic rhinitis. We compared GT terms related to ragweed pollen allergy in American and European Union countries with a known ragweed pollen season. Our aim was to assess seasonality and the terms needed to perform the GT searches and to compare these during the spring and summer pollen seasons. We examined GT queries from January 1, 2011, to January 4, 2017. We included 15 countries with a known ragweed pollen season and used the standard 5-year GT graphs. We used the GT translation for all countries and the untranslated native terms for each country. The results of "pollen," "ragweed," and "allergy" searches differed between countries, but "ragweed" was clearly identified in 12 of the 15 countries. There was considerable heterogeneity of findings when the GT translation was used. For Croatia, Hungary, Romania, Serbia, and Slovenia, the GT translation was inappropriate. The country patterns of "pollen," "hay fever," and "allergy" differed in 8 of the 11 countries with identified "ragweed" queries during the spring and the summer, indicating that the perception of tree and grass pollen allergy differs from that of ragweed pollen. To investigate ragweed pollen allergy using GT, the term "ragweed" as a plant is required and the translation of "ragweed" in the native language needed. © 2018 S. Karger AG, Basel.

  10. Estrogen Drives Cellular Transformation and Mutagenesis in Cells Expressing the Breast Cancer-Associated R438W DNA Polymerase Lambda Protein.

    PubMed

    Nemec, Antonia A; Bush, Korie B; Towle-Weicksel, Jamie B; Taylor, B Frazier; Schulz, Vincent; Weidhaas, Joanne B; Tuck, David P; Sweasy, Joann B

    2016-11-01

    Repair of DNA damage is critical for maintaining the genomic integrity of cells. DNA polymerase lambda (POLL/Pol λ) is suggested to function in base excision repair (BER) and nonhomologous end-joining (NHEJ), and is likely to play a role in damage tolerance at the replication fork. Here, using next-generation sequencing, it was discovered that the POLL rs3730477 single-nucleotide polymorphism (SNP) encoding R438W Pol λ was significantly enriched in the germlines of breast cancer patients. Expression of R438W Pol λ in human breast epithelial cells induces cellular transformation and chromosomal aberrations. The role of estrogen was assessed as it is commonly used in hormone replacement therapies and is a known breast cancer risk factor. Interestingly, the combination of estrogen treatment and the expression of the R438W Pol λ SNP drastically accelerated the rate of transformation. Estrogen exposure produces 8-oxoguanine lesions that persist in cells expressing R438W Pol λ compared with wild-type (WT) Pol λ-expressing cells. Unlike WT Pol λ, which performs error-free bypass of 8-oxoguanine lesions, expression of R438W Pol λ leads to an increase in mutagenesis and replicative stress in cells treated with estrogen. Together, these data suggest that individuals who carry the rs3730477 POLL germline variant have an increased risk of estrogen-associated breast cancer. The Pol λ R438W mutation can serve as a biomarker to predict cancer risk and implicates that treatment with estrogen in individuals with this mutation may further increase their risk of breast cancer. Mol Cancer Res; 14(11); 1068-77. ©2016 AACR. ©2016 American Association for Cancer Research.

  11. The relationship between IR, optical, and UV extinction

    NASA Technical Reports Server (NTRS)

    Cardelli, Jason A.; Clayton, Geoffrey C.; Mathis, John S.

    1989-01-01

    An analysis is presented for the variability of absolute IR, optical, and UV extinction, A(sub lambda), derived through the ratio of total-to-selective extinction, R, for 31 lines of sight for which reliable UV extinction parameters were derived. These data sample a wide range of environments and are characterized by 2.5 is less than or equal to R is less than or equal to 6.0. It was found that there is a strong linear dependence between extinction expressed as A(sub lambda)/A(sub V) and 1/R for 1.25 micron is less than or equal to lambda is less than or equal to 0.12 micron. Differences in the general shape of extinction curves are largely due to variations in shape of optical/near-UV extinction corresponding to changes in R, with A(sub lambda)/A(sub V) decreasing for increasing R. From a least-squares fit of the observed R-dependence as a function of wavelength for 0.8/micron is less than or greater than 1/lambda is less than or equal to 8.3/micron, an analytic expression was generated from which IR, optical, and UV extinction curves of the form A(sub lambda)/A(sub V) can be reproduced with reasonable accuracy from a knowledge of R. It was also found that the absolute bump strength normalized to A(sub V) shows a general decrease with increasing R, suggesting that some fraction of bump grains may be selectively incorporated into coagulated grains. Finally, it was found that absolute extinction normalized by suitably chosen color indices results in a minimization of the R-dependence of portions of the UV curve, allowing A(sub lambda) to be estimated for these wavelengths independent of R.

  12. Proteomic analyses reveal the key roles of BrlA and AbaA in biogenesis of gliotoxin in Aspergillus fumigatus

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

    Shin, Kwang-Soo, E-mail: shinks@dju.kr; Kim, Young Hwan; Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 305-764

    2015-07-31

    The opportunistic human pathogenic fungus Aspergillus fumigatus primarily reproduces by forming a large number of asexual spores (conidia). Sequential activation of the central regulators BrlA, AbaA and WetA is necessary for the fungus to undergo asexual development. In this study, to address the presumed roles of these key developmental regulators during proliferation of the fungus, we analyzed and compared the proteomes of vegetative cells of wild type (WT) and individual mutant strains. Approximately 1300 protein spots were detectable from 2-D electrophoresis gels. Among these, 13 proteins exhibiting significantly altered accumulation levels were further identified by ESI-MS/MS. Markedly, we found thatmore » the GliM and GliT proteins associated with gliotoxin (GT) biosynthesis and self-protection of the fungus from GT were significantly down-regulated in the ΔabaA and ΔbrlA mutants. Moreover, mRNA levels of other GT biosynthetic genes including gliM, gliP, gliT, and gliZ were significantly reduced in both mutant strains, and no and low levels of GT were detectable in the ΔbrlA and ΔabaA mutant strains, respectively. As GliT is required for the protection of the fungus from GT, growth of the ΔbrlA mutant with reduced levels of GliT was severely impaired by exogenous GT. Our studies demonstrate that AbaA and BrlA positively regulate expression of the GT biosynthetic gene cluster in actively growing vegetative cells, and likely bridge morphological and chemical development during the life-cycle of A. fumigatus. - Highlights: • Proteome analyses of WT and mutants reveal 13 differentially expressed proteins. • The GliT and GliM proteins are significantly down-regulated by ΔabaA and ΔbrlA. • Expression of other gliotoxin biosynthetic genes is lowered by ΔabaA and ΔbrlA. • Growth of ΔbrlA strain lacking GliT is completely inhibited by exogenous gliotoxin. • BrlA and AbaA play key roles in biogenesis of gliotoxin in Aspergillus fumigatus.« less

  13. Mass Changes of the Greenland and Antarctic Ice Sheets and Shelves and Contributions to Sea-level Rise: 1992-2002

    NASA Technical Reports Server (NTRS)

    Zwally, H. Jay; Giovinetto, Mario B.; Li, Jun; Cornejo, Helen G.; Beckley, Matthew A.; Brenner, Anita C.; Saba, Jack L.; Yi, Donghui

    2005-01-01

    Changes in ice mass are estimated from elevation changes derived from 10.5 years (Greenland) and 9 years (Antarctica) of satellite radar altimetry data from the European Remote-sensing Satellites ERS-1 and -2. For the first time, the dH/dt values are adjusted for changes in surface elevation resulting from temperature-driven variations in the rate of fun compaction. The Greenland ice sheet is thinning at the margins (-42 plus or minus 2 Gta(sup -1) below the equilibrium line altitude (ELA)) and growing inland (+53 plus or minus 2 Gt a(sup -1)above the ELA) with a small overall mass gain (+11 plus or minus 3 Gt a(sup -1); -0.03 mm a(sup -1) SLE (sea level equivalent)). The ice sheet in West Antarctica (WA) is losing mass (-47 (dot) 4 GT a(sup -1) and the ice sheet in East Antarctica (EA) shows a small mass gain (+16 plus or minus 11 Gt a(sup -1) for a combined net change of -31 plus or minus 12 Gt a(sup -1) (+0.08 mm a(sup -1) SLE)). The contribution of the three ice sheets to sea level is +0.05 plus or minus 0.03 mm a(sup -1). The Antarctic ice shelves show corresponding mass changes of -95 (dot) 11 Gt a(sup -1) in WA and +142 plus or minus 10 Gt a(sup -1) in EA. Thinning at the margins of the Greenland ice sheet and growth at higher elevations is an expected response to increasing temperatures and precipitation in a warming climate. The marked thinnings in the Pine Island and Thwaites Glacier basins of WA and the Totten Glacier basin in EA are probably ice-dynamic responses to long-term climate change and perhaps past removal of their adjacent ice shelves. The ice growth in the southern Antarctic Peninsula and parts of EA may be due to increasing precipitation during the last century.

  14. Genomic structure, promoter identification, and chromosomal mapping of a mouse nuclear orphan receptor expressed in embryos and adult testes

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

    Lee, C.H.; Wei, Li-Na; Copeland, N.G.

    We have isolated and characterized overlapping genomic clones containing the complete transcribed region of a newly isolated mouse cDNA encoding an orphan receptor expressed specifically in midgestation embryos and adult testis. This gene spans a distance of more than 50 kb and is organized into 13 exons. The transcription initiation site is located at the 158th nucleotide upstream from the translation initiation codon. All the exon/intron junction sequences follow the GT/AG rule. Based upon Northern blot analysis and the size of the transcribed region of the gene, its transcript was determined to be approximately 2.5 kb. Within approximately 500 hpmore » upstream from the transcription initiation site, several immune response regulatory elements were identified but no TATA box was located. This gene was mapped to the distal region of mouse chromosome 10 and its locus has been designated Tr2-11. Immunohistochemical studies show that the Tr2-11 protein is present mainly in advanced germ cell populations of mature testes and that Tr2-11 gene expression is dramatically decreased in vitamin A-depleted animals. 23 refs., 7 figs.« less

  15. Reduction of Radiation-Induced Vascular Nitrosative Stress by the Vitamin E Analog {gamma}-Tocotrienol: Evidence of a Role for Tetrahydrobiopterin

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

    Berbee, Maaike; Fu Qiang; Boerma, Marjan

    2011-03-01

    Purpose: The vitamin E analog {gamma}-tocotrienol (GT3) is a powerful radioprotector. GT3 reduces postradiation vascular peroxynitrite production, an effect dependent on inhibition of hydroxy-methylglutaryl-coenzyme A reductase. Hydroxy-methylglutaryl-coenzyme A reductase inhibitors mediate their pleiotropic effects via endothelial nitric oxide synthase that requires the cofactor tetrahydrobiopterin (BH4). This study investigated the effects of radiation on BH4 bioavailability and of GT3 on BH4 metabolism. Methods and Materials: Mice were exposed to 8.5 Gy of total body irradiation (TBI). Lung BH4 and total biopterin concentrations were measured 0, 3.5, 7, 14, and 21 days after TBI by use of differential oxidation followed by high-performancemore » liquid chromatography. The effect of exogenous GT3 and BH4 treatment on postradiation vascular oxidative stress and bone marrow colony-forming units were assessed in vivo. The effect of GT3 on endothelial cell apoptosis and endothelial expression of guanosine triphosphate (GTP) cyclohydrolase 1 (GTPCH), GTPCH feedback regulatory protein (GFRP), GFRP transcription, GFRP protein levels, and GFRP-GTPCH protein binding was determined in vitro. Results: Compared with baseline levels, lung BH4 concentrations decreased by 24% at 3.5 days after TBI, an effect that was reversed by GT3. At 14 and 21 days after TBI, compensatory increases in BH4 (58% and 80%, respectively) were observed. Relative to vehicle-treated controls, both GT3 and BH4 supplementation reduced postirradiation vascular peroxynitrite production at 3.5 days (by 66% and 33%, respectively), and BH4 resulted in a 68% increase in bone marrow colony-forming units. GT3 ameliorated endothelial cell apoptosis and reduced endothelial GFRP protein levels and GFRP-GTPCH binding by decreasing transcription of the GFRP gene. Conclusions: BH4 bioavailability is reduced in the early postradiation phase. Exogenous administration of BH4 reduces postirradiation vascular oxidative stress. GT3 potently reduces the expression of GFRP, one of the key regulatory proteins in the BH4 pathway, and may thus exert some of its beneficial effects on postradiation free radical production partly by counteracting the decrease in BH4.« less

  16. Starspot evolution, differential rotation, and magnetic cycles in the chromospherically active binaries lambda andromedae, sigma Geminorum, II Pegasi, and V711 Tauri

    NASA Technical Reports Server (NTRS)

    Henry, Gregory W.; Eaton, Joel A.; Hamer, Jamesia; Hall, Douglas S.

    1995-01-01

    We have analyzed 15-19 yr of photoelectric photometry, obtained manually and with automated telescopes, of the chromospherically active binaries lambda And, sigma Gem, II Peg, and V711 Tau. These observations let us identify individual dark starspots on the stellar surfaces from periodic dimming of the starlight, follow the evolution of these spots, and search for long-term cyclic changes in the properties of these starspots that might reveal magnetic cycles analogous to the Sun's 11 yr sunspot cycle. We developed a computer code to fit a simple two-spot model to our observed light curves that allows us to extract the most easily determinable and most reliable spot parameters from the light curves, i.e., spot longitudes and radii. We then used these measured properties to identify individual spots and to chart their life histories by constructing migration and amplitude curves. We identified and followed 11 spots in lambda And, 16 in sigma Gem, 12 in II Peg, and 15 in V711 Tau. Lifetimes of individual spots ranged from a few months to longer than 6 yr. Differential rotation coefficients, estimated from the observed range of spot rotation periods for each star and defined by equation (2), were 0.04 for lambda And, 0.038 for sigma Gem, 0.005 for II Peg, and 0.006 for V711 Tau, versus 0.19 for the Sun. We searched for cyclic changes in mean brightness, B-V color index, and spot rotation period as evidence for long-term cycles. Of these, long-term variability in mean brightness appears to offer the best evidence for such cycles in these four stars. Cycles of 11.1 yr for lambda And, 8.5 yr for sigma Gem, 11 yr for II Peg, and 16 yr V711 Tau are implied by these mean brightness changes. Cyclic changes in spot rotation period were found in lambda And and possibly II Peg. Errors in B-V were too large for any long-term changes to be detectable.

  17. Resistance Analyses of Japanese Hepatitis C-Infected Patients Receiving Sofosbuvir or Ledipasvir/Sofosbuvir Containing Regimens in Phase 3 Studies.

    PubMed

    Mizokami, M; Dvory-Sobol, H; Izumi, N; Nishiguchi, S; Doehle, B; Svarovskaia, E S; De-Oertel, S; Knox, S; Brainard, D M; Miller, M D; Mo, H; Sakamoto, N; Takehara, T; Omata, M

    2016-10-01

    High rates of sustained virologic response (SVR) has been achieved in Japanese patients with chronic hepatitis C virus (HCV) genotype (GT)1 and GT2 infection treated with ledipasvir/sofosbuvir (LDV/SOF) ±ribavirin (RBV) and SOF+RBV, respectively. We evaluated the effect of baseline HCV NS5A and NS5B resistance-associated variants (RAVs) on treatment outcome and characterized variants at virologic failure. Baseline deep sequencing for NS5A and NS5B genes was performed for all GT1 patients. Deep sequencing of NS5A (GT1 only) and NS5B (GT1 and GT2) was performed for patients who failed treatment or discontinued early with detectable HCV RNA (i.e., >25 IU/mL). In patients with HCV GT1 infection, 22.3% (GT1a: 2/11; GT1b: 74/330) had ≥1 baseline NS5A RAV. The most frequent NS5A RAVs in GT1b were Y93H (17.9%, 59/330) and L31M (2.4%, 8/330). Despite the presence of NS5A RAVs at baseline, 100% and 97% of patients achieved SVR12, compared with 100% and 99% for those with no NS5A RAVs with LDV/SOF and LDV/SOF+RBV, respectively. All patients with NS5B RAVs at baseline achieved SVR12. Of the 153 patients with GT2 infection (GT2a 60.1%, GT2b 39.9%), 3.3% (5/153) experienced viral relapse. No S282T or other NS5B RAVs were detected at baseline or relapse; no change in susceptibility to SOF or RBV was observed at relapse. In conclusion, LDV/SOF and SOF+RBV demonstrate a high barrier to resistance in Japanese patients with HCV GT1 and GT2 infection. The presence of baseline NS5A RAVs did not impact treatment outcome in GT1 Japanese patients treated with LDV/SOF for 12 weeks. © 2016 John Wiley & Sons Ltd.

  18. Glycosyl transferases in family 61 mediate arabinofuranosyl transfer onto xylan in grasses.

    PubMed

    Anders, Nadine; Wilkinson, Mark D; Lovegrove, Alison; Freeman, Jacqueline; Tryfona, Theodora; Pellny, Till K; Weimar, Thilo; Mortimer, Jennifer C; Stott, Katherine; Baker, John M; Defoin-Platel, Michael; Shewry, Peter R; Dupree, Paul; Mitchell, Rowan A C

    2012-01-17

    Xylan, a hemicellulosic component of the plant cell wall, is one of the most abundant polysaccharides in nature. In contrast to dicots, xylan in grasses is extensively modified by α-(1,2)- and α-(1,3)-linked arabinofuranose. Despite the importance of grass arabinoxylan in human and animal nutrition and for bioenergy, the enzymes adding the arabinosyl substitutions are unknown. Here we demonstrate that knocking-down glycosyltransferase (GT) 61 expression in wheat endosperm strongly decreases α-(1,3)-linked arabinosyl substitution of xylan. Moreover, heterologous expression of wheat and rice GT61s in Arabidopsis leads to arabinosylation of the xylan, and therefore provides gain-of-function evidence for α-(1,3)-arabinosyltransferase activity. Thus, GT61 proteins play a key role in arabinoxylan biosynthesis and therefore in the evolutionary divergence of grass cell walls.

  19. Heterogeneous and monoclonal helper T cells induce similar anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) antibody populations in the primary adoptive response. II. Lambda light chain dominance and idiotope expression.

    PubMed

    Smith, F I; Tesch, H; Rajewsky, K

    1984-02-01

    When the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP) is presented on different carrier molecules, different anti-NP antibody responses are stimulated. On stimulation with NP-lipopolysaccharide (LPS) [T-independent type 1 (TI-1) antigen] kappa + antibodies are the major population, whereas on stimulation with NP-Ficoll [T-independent type 2 (TI-2) antigen], NP-keyhole limpet hemocyanin (KLH) or NP-chicken gamma globulin (CG) [T-dependent (TD) antigens], lambda 1+ antibodies dominate. The relative contribution of idiotopes Ac38 or Ac146 to the lambda 1+ anti-NP response was also different on comparison of TI-1 with TI-2 or TD anti-NP responses. We investigated whether light chain- or idiotype-specific T cells are responsible for these differences. Analysis of the anti-NP response of nude mice after immunization with NP-Ficoll showed lambda 1 dominance. Likewise primary adoptive transfer experiments using carrier-specific T cell lines to reconstitute the TD anti-NP response to NP-KLH or NP-CG, showed that help from carrier-specific T cells alone is capable of stimulating the characteristic lambda 1 dominant response. No significant difference could be found in the levels of Ac38 and Ac146 idiotope expression between mice reconstituted with splenic T cells and those reconstituted with T cell lines. These results suggest that light chain- or idiotype-specific T cells are required neither for the production of lambda 1 light chain dominance, nor for the appearance of idiotopes characteristic of the primary anti-NP response. The possible reasons for differences seen in both light chain and idiotope expression between primary anti-NP responses to the TI-1 antigen NP-LPS and those to TD or TI-2 antigens are discussed.

  20. Preliminary use of nematic liquid crystal adaptive optics with a 2.16-meter reflecting telescope.

    PubMed

    Cao, Zhaoliang; Mu, Quanquan; Hu, Lifa; Li, Dayu; Peng, Zenghui; Liu, Yonggang; Xuan, Li

    2009-02-16

    A nematic liquid crystal adaptive optics system (NLC AOS) was assembled for a 2.16-m telescope to correct for atmospheric turbulence. LC AOS was designed and optimized with Zemax optical software. Second, an adaptive correction experiment was performed in the laboratory to test the performance of the NLC AOS. After the correction, the peak to valley (PV) and root mean square (RMS) of the wavefront were down to 0.2 lambda (lambda=633 nm) and 0.05 lambda, respectively. Finally, the star of Pollux (beta Gem) was tracked using the 2.16-m Reflecting Telescope, and real time correction of the atmospheric turbulence was performed with the NLC AOS. After the adaptive correction, the average PV and RMS of the wavefront were reduced from 11 lambda and 2.5 lambda to 2.3 lambda and 0.6 lambda, respectively. Although the intensity distribution of the beta Gem was converged and its peak was sharp, a halo still existed around the peak. These results indicated that the NLC AOS only partially corrected the vertical atmospheric turbulence. The limitations of our NLC AOS are discussed and some proposals are made.

  1. Observation of the Heavy Baryons Sigma b and Sigma b*.

    PubMed

    Aaltonen, T; Abulencia, A; Adelman, J; Affolder, T; Akimoto, T; Albrow, M G; Amerio, S; Amidei, D; Anastassov, A; Anikeev, K; Annovi, A; Antos, J; Aoki, M; Apollinari, G; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Aurisano, A; Azfar, F; Azzi-Bacchetta, P; Azzurri, P; Bacchetta, N; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Baroiant, S; Bartsch, V; Bauer, G; Beauchemin, P-H; Bedeschi, F; Behari, S; Bellettini, G; Bellinger, J; Belloni, A; Benjamin, D; Beretvas, A; Beringer, J; Berry, T; Bhatti, A; Binkley, M; Bisello, D; Bizjak, I; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bolshov, A; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Byrum, K L; Cabrera, S; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carillo, S; Carlsmith, D; Carosi, R; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, I; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Cilijak, M; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Coca, M; Compostella, G; Convery, M E; Conway, J; Cooper, B; Copic, K; Cordelli, M; Cortiana, G; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; DaRonco, S; Datta, M; D'Auria, S; Davies, T; Dagenhart, D; de Barbaro, P; De Cecco, S; Deisher, A; De Lentdecker, G; De Lorenzo, G; Dell'Orso, M; Delli Paoli, F; Demortier, L; Deng, J; Deninno, M; De Pedis, D; Derwent, P F; Di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Dörr, C; Donati, S; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, I; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Field, R; Flanagan, G; Forrest, R; Forrester, S; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garcia, J E; Garberson, F; Garfinkel, A F; Gay, C; Gerberich, H; Gerdes, D; Giagu, S; Giannetti, P; Gibson, K; Gimmell, J L; Ginsburg, C; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Goldstein, J; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Grinstein, S; Grosso-Pilcher, C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Hamilton, A; Han, B-Y; Han, J Y; Handler, R; Happacher, F; Hara, K; Hare, D; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hauser, J; Hays, C; Heck, M; Heijboer, A; Heinemann, B; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Holloway, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ivanov, A; Iyutin, B; James, E; Jang, D; Jayatilaka, B; Jeans, D; Jeon, E J; Jindariani, S; Johnson, W; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Karchin, P E; Kato, Y; Kemp, Y; Kephart, R; Kerzel, U; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Klute, M; Knuteson, B; Ko, B R; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kraan, A C; Kraus, J; Kreps, M; Kroll, J; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhlmann, S E; Kuhr, T; Kulkarni, N P; Kusakabe, Y; Kwang, S; Laasanen, A T; Lai, S; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; LeCompte, T; Lee, J; Lee, J; Lee, Y J; Lee, S W; Lefèvre, R; Leonardo, N; Leone, S; Levy, S; Lewis, J D; Lin, C; Lin, C S; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Lu, R-S; Lucchesi, D; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Lytken, E; Mack, P; MacQueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Malik, S; Manca, G; Manousakis, A; Margaroli, F; Marginean, R; Marino, C; Marino, C P; Martin, A; Martin, M; Martin, V; Martínez, M; Martínez-Ballarín, R; Maruyama, T; Mastrandrea, P; Masubuchi, T; Matsunaga, H; Mattson, M E; Mazini, R; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzemer, S; Menzione, A; Merkel, P; Mesropian, C; Messina, A; Miao, T; Miladinovic, N; Miles, J; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyamoto, A; Moed, S; Moggi, N; Mohr, B; Moon, C S; Moore, R; Morello, M; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Mussini, M; Nachtman, J; Nagano, A; Naganoma, J; Nakamura, K; Nakano, I; Napier, A; Necula, V; Neu, C; Neubauer, M S; Nielsen, J; Nodulman, L; Norniella, O; Nurse, E; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Oldeman, R; Orava, R; Osterberg, K; Pagliarone, C; Palencia, E; Papadimitriou, V; Papaikonomou, A; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Piedra, J; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Portell, X; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Reisert, B; Rekovic, V; Renton, P; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Roy, P; Ruiz, A; Russ, J; Rusu, V; Saarikko, H; Safonov, A; Sakumoto, W K; Salamanna, G; Saltó, O; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savard, P; Savoy-Navarro, A; Scheidle, T; Schlabach, P; Schmidt, E E; Schmidt, M A; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scott, A L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sfyrla, A; Shalhout, S Z; Shapiro, M D; Shears, T; Shepard, P F; Sherman, D; Shimojima, M; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soderberg, M; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spinella, F; Spreitzer, T; Squillacioti, P; Stanitzki, M; Staveris-Polykalas, A; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Stuart, D; Suh, J S; Sukhanov, A; Sun, H; Suslov, I; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Tesarek, R J; Thom, J; Thompson, A S; Thomson, E; Tipton, P; Tiwari, V; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Tourneur, S; Trischuk, W; Tsuno, S; Tu, Y; Turini, N; Ukegawa, F; Uozumi, S; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vazquez, F; Velev, G; Vellidis, C; Veramendi, G; Veszpremi, V; Vidal, M; Vidal, R; Vila, I; Vilar, R; Vine, T; Vogel, M; Vollrath, I; Volobouev, I; Volpi, G; Würthwein, F; Wagner, P; Wagner, R G; Wagner, R L; Wagner, J; Wagner, W; Wallny, R; Wang, S M; Warburton, A; Waters, D; Weinberger, M; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Wynne, S M; Yagil, A; Yamamoto, K; Yamaoka, J; Yamashita, T; Yang, C; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zaw, I; Zhang, X; Zhou, J; Zucchelli, S

    2007-11-16

    We report an observation of new bottom baryons produced in pp collisions at the Tevatron. Using 1.1 fb(-1) of data collected by the CDF II detector, we observe four Lambda b 0 pi+/- resonances in the fully reconstructed decay mode Lambda b 0-->Lambda c + pi-, where Lambda c+-->pK* pi+. We interpret these states as the Sigma b(*)+/- baryons and measure the following masses: m Sigma b+=5807.8 -2.2 +2.0(stat.)+/-1.7(syst.) MeV/c2, m Sigma b- =5815.2+/-1.0(stat.)+/-1.7(syst.) MeV/c2, and m(Sigma b*)-m(Sigma b)=21.2-1.9 +2.0(stat.)-0.3+0.4(syst.) MeV/c2.

  2. Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene mutations in North Egyptian population: implications for the genetic diagnosis in Egypt.

    PubMed

    El-Seedy, A; Pasquet, M C; Shafiek, H; Morsi, T; Kitzis, A; Ladevèze, V

    2016-11-30

    Cystic fibrosis (CF) occurrence in Arab populations is not common and still remains underidentified. Furthermore, the lack of disease awareness and diagnosis facilities have mislead the identification of cystic fibrosis for decades. The knowledge about cystic fibrosis (CF) in Egypt is very limited, and a few reports have drawn attention to the existence of CF or CFTR-related disorders (CFTR-RDs) in the Egyptian population. Therefore a comprehensive genetic analysis of the CFTR gene was realized in patients of North Egypt. DNA samples of 56 Egyptian patients were screened for the CFTR gene mutations. The 27 exons and their flanking regions of the CFTR gene were amplified by PCR, using the published primer pairs, and were studied by automated direct DNA sequencing to detect disease-causing mutations. Moreover, large duplication/deletion was analysed by MLPA technique. CFTR screening revealed the identification of thirteen mutations including four novel ones: c.92G>A (p.Arg31His), c.2782G>C (p.Ala928Pro), c.3718-24G>A, c.4207A>G (p.Arg1403Gly) and nine previously reported mutations: c.454A>T (p.Met152Leu), c.902A>G (p.Tyr301Cys), c.1418delG, c.2620-15C>G, c.2997_3000delAATT, c.3154T>G (p.Phe1052Val), c.3872A>G (p.Gln1291Arg), c.3877G>A (p.Val1293Ile), c.4242+10T>C. Furthermore, eight polymorphisms were found: c.743+40A>G, c.869+11C>T, c.1408A>G, c.1584G>A, c.2562T>G, c.3870A>G, c.4272C>T, c.4389G>A. These mutations and polymorphisms were not previously described in the Egyptian population except for the c.1408A>G polymorphism. Here we demonstrate the importance of the newly discovered mutations in Egyptian patients and the presence of CF, whereas the p.Phe508del mutation is not detected. The identification of CFTR mutations will become increasingly important in undocumented populations. The current findings will help us expand the mutational spectrum of CF and establish the first panel of the CFTR gene mutations in the Egyptian population and design an appropriate strategy for future genetic diagnosis of CF.

  3. An analysis of the polymorphisms of the GLUT1 gene in urothelial cell carcinomas of the bladder and its correlation with p53, Ki67 and GLUT1 expressions.

    PubMed

    Xu, C; Yang, X; Wang, Y; Ding, N; Han, R; Sun, Y; Wang, Y

    2017-07-01

    Frequencies of two glucose transporter 1 (GLUT1) single-nucleotide polymorphisms (SNPs) (XbaI G>T and HaeIII T>C) were studied with urothelial cell carcinomas of the bladder (UCC) and 204 normal persons. And the expression of the p53, Ki67 and GLUT1 was assayed by immunohistochemistry. The frequency of the TT genotype and T allele of the XbaI G>T SNP was decreased in the patients with UCC. The frequency of the CC genotype and C allele of the HaeIII T>C SNP was decreased in the patients with UCC. The GLUT1 XbaI genotype GG was more frequent in higher tumor stage and higher tumor grade patients. In the XbaI G>T SNP, the GG genotype was significantly related to higher Remmele immunoreactive score (IRS) of Ki67 and higher IRS of GLUT1. In conclusion, the TT genotype in XbaI G>T SNP and CC genotype of HaeIII T>C SNP may have protective effect in the carcinogenesis process of UCC. In the XbaI G>T SNP, the GG genotype of was positively related to tumor proliferation, glucose metabolism, tumor grade and stage. Therefore, the variant might become a possible proliferation-related prognostic factor for UCC.

  4. Expression of HIV-Tat protein is associated with learning and memory deficits in the mouse

    PubMed Central

    Carey, Amanda N.; Sypek, Elizabeth I.; Singh, Harminder D.; Kaufman, Marc J.; McLaughlin, Jay P.

    2012-01-01

    HIV-Tat protein has been implicated in the pathogenesis of HIV-1 neurological complications (i.e., neuroAIDS), but direct demonstrations of the effects of Tat on behavior are limited. GT-tg mice with a doxycycline (Dox)-inducible and brain-selective tat gene coding for Tat protein were used to test the hypothesis that the activity of Tat in brain is sufficient to impair learning and memory processes. Western blot analysis of GT-tg mouse brains demonstrated an increase in Tat antibody labeling that seemed to be dependent on the dose and duration of Dox pretreatment. Dox-treated GT-tg mice tested in the Barnes maze demonstrated longer latencies to find an escape hole and displayed deficits in probe trial performance, versus uninduced GT-tg littermates, suggesting Tat-induced impairments of spatial learning and memory. Reversal learning was also impaired in Tat-induced mice. Tat-induced mice additionally demonstrated long-lasting (up to one month) deficiencies in novel object recognition learning and memory performance. Furthermore, novel object recognition impairment was dependent on the dose and duration of Dox exposure, suggesting that Tat exposure progressively mediated deficits. These experiments provide evidence that Tat protein expression is sufficient to mediate cognitive abnormalities seen in HIV-infected individuals. Moreover, the genetically engineered GT-tg mouse may be useful for improving our understanding of the neurological underpinnings of neuroAIDS-related behaviors. PMID:22197678

  5. Microconnectomics of the pretectum and ventral thalamus in the chicken (Gallus gallus).

    PubMed

    Vega-Zuniga, Tomas; Marín, Gonzalo; González-Cabrera, Cristian; Planitscher, Eva; Hartmann, Anja; Marks, Vanessa; Mpodozis, Jorge; Luksch, Harald

    2016-08-01

    The avian pretectal and ventrothalamic nuclei, encompassing the griseum tectale (GT), n. lentiformis mesencephali (LM), and n. geniculatus lateralis pars ventralis (GLv), are prominent retinorecipient structures related to optic flow operations and visuomotor control. Hence, a close coordination of these neural circuits is to be expected. Yet the connectivity among these nuclei is poorly known. Here, using intracellular labeling and in situ hybridization, we investigated the detailed morphology, connectivity, and neurochemical identity of neurons in these nuclei. Two different cell types exist in the GT: one that generates an axonal projection to the optic tectum (TeO), LM, GLv, and n. intercalatus thalami (ICT), and a second population that only projects to the LM and GLv. In situ hybridization revealed that most neurons in the GT express the vesicular glutamate transporter (VGluT2) mRNA, indicating a glutamatergic identity. In the LM, three morphological cell types were defined, two of which project axons towards dorsal targets. The LM neurons showed strong VGluT2 expression. Finally, the cells located in the GLv project to the TeO, LM, GT, n. principalis precommisuralis (PPC), and ICT. All neurons in the GLv showed strong expression of the vesicular inhibitory amino acid transporter (VIAAT) mRNA, suggesting a GABAergic identity. Our results show that the pretectal and ventrothalamic nuclei are highly interconnected, especially by glutamatergic and GABAergic neurons from the GT and GLv, respectively. This complex morphology and connectivity might be required to organize orienting visuomotor behaviors and coordinate the specific optic flow patterns that they induce. J. Comp. Neurol. 524:2208-2229, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  6. Perspectives on fish gonadotropins and their receptors.

    PubMed

    Levavi-Sivan, B; Bogerd, J; Mañanós, E L; Gómez, A; Lareyre, J J

    2010-02-01

    Teleosts lack a hypophyseal portal system and hence neurohormones are carried by nerve fibers from the preoptic region to the pituitary. The various cell types in the teleost pituitary are organized in discrete domains. Fish possess two gonadotropins (GtH) similar to FSH and LH in other vertebrates; they are heterodimeric hormones that consist of a common alpha subunit non-covalently associated with a hormone-specific beta subunit. In recent years the availability of molecular cloning techniques allowed the isolation of the genes coding for the GtH subunits in 56 fish species representing at least 14 teleost orders. Advanced molecular engineering provides the technology to produce recombinant GtHs from isolated cDNAs. Various expression systems have been used for the production of recombinant proteins. Recombinant fish GtHs were produced for carp, seabream, channel and African catfish, goldfish, eel, tilapia, zebrafish, Manchurian trout and Orange-spotted grouper. The hypothalamus in fishes exerts its regulation on the release of the GtHs via several neurohormones such as GnRH, dopamine, GABA, PACAP, IGF-I, norepinephrine, NPY, kisspeptin, leptin and ghrelin. In addition, gonadal steroids and peptides exert their effects on the gonadotropins either directly or via the hypothalamus. All these are discussed in detail in this review. In mammals, the biological activities of FSH and LH are directed to different gonadal target cells through the cell-specific expression of the FSH receptor (FSHR) and LH receptor (LHR), respectively, and the interaction between each gonadotropin-receptor couple is highly selective. In contrast, the bioactivity of fish gonadotropins seems to be less specific as a result of promiscuous hormone-receptor interactions, while FSHR expression in Leydig cells explains the strong steroidogenic activity of FSH in certain fish species. Copyright 2009 Elsevier Inc. All rights reserved.

  7. Circadian gene expression regulates pulsatile gonadotropin-releasing hormone (GnRH) secretory patterns in the hypothalamic GnRH-secreting GT1-7 cell line.

    PubMed

    Chappell, Patrick E; White, Rachel S; Mellon, Pamela L

    2003-12-03

    Although it has long been established that episodic secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus is required for normal gonadotropin release, the molecular and cellular mechanisms underlying the synchronous release of GnRH are primarily unknown. We used the GT1-7 mouse hypothalamic cell line as a model for GnRH secretion, because these cells release GnRH in a pulsatile pattern similar to that observed in vivo. To explore possible molecular mechanisms governing secretory timing, we investigated the role of the molecular circadian clock in regulation of GnRH secretion. GT1-7 cells express many known core circadian clock genes, and we demonstrate that oscillations of these components can be induced by stimuli such as serum and the adenylyl cyclase activator forskolin, similar to effects observed in fibroblasts. Strikingly, perturbation of circadian clock function in GT1-7 cells by transient expression of the dominant-negative Clock-Delta19 gene disrupts normal ultradian patterns of GnRH secretion, significantly decreasing mean pulse frequency. Additionally, overexpression of the negative limb clock gene mCry1 in GT1-7 cells substantially increases GnRH pulse amplitude without a commensurate change in pulse frequency, demonstrating that an endogenous biological clock is coupled to the mechanism of neurosecretion in these cells and can regulate multiple secretory parameters. Finally, mice harboring a somatic mutation in the Clock gene are subfertile and exhibit a substantial increase in estrous cycle duration as revealed by examination of vaginal cytology. This effect persists in normal light/dark (LD) cycles, suggesting that a suprachiasmatic nucleus-independent endogenous clock in GnRH neurons is required for eliciting normal pulsatile patterns of GnRH secretion.

  8. Autofluorescence spectroscopy of oral mucosa

    NASA Astrophysics Data System (ADS)

    Majumdar, S. K.; Uppal, A.; Gupta, P. K.

    1998-06-01

    We report the results of an in-vitro study on autofluorescence from pathologically characterized normal and malignant squamous tissues from the oral cavity. The study involved biopsy samples from 47 patients with oral cancer of which 11 patients had cancer of tongue, 17 of buccal mucosa and 19 of alveolus. The results of excitation and emission spectroscopy at several wavelengths (280 nm less than or equal to (lambda) exless than or equal to 460 nm; 340 nm less than or equal to (lambda) em less than or equal to 520 nm) showed that at (lambda) ex equals 337 nm and 400 nm the mean value for the spectrally integrated fluorescence intensity [(Sigma) (lambda ) IF((lambda) )] from the normal tissue sites was about a factor of 2 larger than that from the malignant tissue sites. At other excitation wavelengths the difference in (Sigma) (lambda ) IF((lambda) ) was not statistically significant. Similarly, for (lambda) em equals 390 nm and 460 nm, the intensity of the 340 nm band of the excitation spectra from normal tissues was observed to be a factor of 2 larger than that from malignant tissues. Analysis of these results suggests that NADH concentration is higher in normal oral tissues compared to the malignant. This contrasts with our earlier observation of an reduced NADH concentration in normal sites of breast tissues vis a vis malignant sites. For the 337 nm excited emission spectra a 10-variable MVLR score (using (Sigma) (lambda ) IF((lambda) ) and normalized intensities at nine wavelengths as input parameters) provided a sensitivity and specificity of 95.7% and 93.1% over the sample size investigated.

  9. Formation of β-glucogallin, the precursor of ellagic acid in strawberry and raspberry

    PubMed Central

    Schulenburg, Katja; Feller, Antje; Hoffmann, Thomas; Schecker, Johannes H.; Martens, Stefan; Schwab, Wilfried

    2016-01-01

    Ellagic acid/ellagitannins are plant polyphenolic antioxidants that are synthesized from gallic acid and have been associated with a reduced risk of cancer and cardiovascular diseases. Here, we report the identification and characterization of five glycosyltransferases (GTs) from two genera of the Rosaceae family (Fragaria and Rubus; F.×ananassa FaGT2*, FaGT2, FaGT5, F. vesca FvGT2, and R. idaeus RiGT2) that catalyze the formation of 1-O-galloyl-β-d-glucopyranose (β-glucogallin) the precursor of ellagitannin biosynthesis. The enzymes showed substrate promiscuity as they formed glucose esters of a variety of (hydroxyl)benzoic and (hydroxyl)cinnamic acids. Determination of kinetic values and site-directed mutagenesis revealed amino acids that affected substrate preference and catalytic activity. Green immature strawberry fruits were identified as the main source of gallic acid, β-glucogallin, and ellagic acid in accordance with the highest GT2 gene expression levels. Injection of isotopically labeled gallic acid into green fruits of stable transgenic antisense FaGT2 strawberry plants clearly confirmed the in planta function. Our results indicate that GT2 enzymes might contribute to the production of ellagic acid/ellagitannins in strawberry and raspberry, and are useful to develop strawberry fruit with additional health benefits and for the biotechnological production of bioactive polyphenols. PMID:26884604

  10. H-2RIIBP, a member of the nuclear hormone receptor superfamily that binds to both the regulatory element of major histocompatibility class I genes and the estrogen response element.

    PubMed

    Hamada, K; Gleason, S L; Levi, B Z; Hirschfeld, S; Appella, E; Ozato, K

    1989-11-01

    Transcription of major histocompatibility complex (MHC) class I genes is regulated by the conserved MHC class I regulatory element (CRE). The CRE has two factor-binding sites, region I and region II, both of which elicit enhancer function. By screening a mouse lambda gt 11 library with the CRE as a probe, we isolated a cDNA clone that encodes a protein capable of binding to region II of the CRE. This protein, H-2RIIBP (H-2 region II binding protein), bound to the native region II sequence, but not to other MHC cis-acting sequences or to mutant region II sequences, similar to the naturally occurring region II factor in mouse cells. The deduced amino acid sequence of H-2RIIBP revealed two putative zinc fingers homologous to the DNA-binding domain of steroid/thyroid hormone receptors. Although sequence similarity in other regions was minimal, H-2RIIBP has apparent modular domains characteristic of the nuclear hormone receptors. Further analyses showed that both H-2RIIBP and the natural region II factor bind to the estrogen response element (ERE) of the vitellogenin A2 gene. The ERE is composed of a palindrome, and half of this palindrome resembles the region II binding site of the MHC CRE. These results indicate that H-2RIIBP (i) is a member of the superfamily of nuclear hormone receptors and (ii) may regulate not only MHC class I genes but also genes containing the ERE and related sequences. Sequences homologous to the H-2RIIBP gene are widely conserved in the animal kingdom. H-2RIIBP mRNA is expressed in many mouse tissues, in agreement with the distribution of the natural region II factor.

  11. Primary structure of prostaglandin G/H synthase from sheep vesicular gland determined from the complementary DNA sequence.

    PubMed Central

    DeWitt, D L; Smith, W L

    1988-01-01

    Prostaglandin G/H synthase (8,11,14-icosatrienoate, hydrogen-donor:oxygen oxidoreductase, EC 1.14.99.1) catalyzes the first step in the formation of prostaglandins and thromboxanes, the conversion of arachidonic acid to prostaglandin endoperoxides G and H. This enzyme is the site of action of nonsteroidal anti-inflammatory drugs. We have isolated a 2.7-kilobase complementary DNA (cDNA) encompassing the entire coding region of prostaglandin G/H synthase from sheep vesicular glands. This cDNA, cloned from a lambda gt 10 library prepared from poly(A)+ RNA of vesicular glands, hybridizes with a single 2.75-kilobase mRNA species. The cDNA clone was selected using oligonucleotide probes modeled from amino acid sequences of tryptic peptides prepared from the purified enzyme. The full-length cDNA encodes a protein of 600 amino acids, including a signal sequence of 24 amino acids. Identification of the cDNA as coding for prostaglandin G/H synthase is based on comparison of amino acid sequences of seven peptides comprising 103 amino acids with the amino acid sequence deduced from the nucleotide sequence of the cDNA. The molecular weight of the unglycosylated enzyme lacking the signal peptide is 65,621. The synthase is a glycoprotein, and there are three potential sites for N-glycosylation, two of them in the amino-terminal half of the molecule. The serine reported to be acetylated by aspirin is at position 530, near the carboxyl terminus. There is no significant similarity between the sequence of the synthase and that of any other protein in amino acid or nucleotide sequence libraries, and a heme binding site(s) is not apparent from the amino acid sequence. The availability of a full-length cDNA clone coding for prostaglandin G/H synthase should facilitate studies of the regulation of expression of this enzyme and the structural features important for catalysis and for interaction with anti-inflammatory drugs. Images PMID:3125548

  12. Defective B cell tolerance in adenosine deaminase deficiency is corrected by gene therapy

    PubMed Central

    Sauer, Aisha V.; Morbach, Henner; Brigida, Immacolata; Ng, Yen-Shing; Aiuti, Alessandro; Meffre, Eric

    2012-01-01

    Adenosine deaminase (ADA) gene defects are among the most common causes of SCID. Restoration of purine metabolism and immune functions can be achieved by enzyme replacement therapy, or more effectively by bone marrow transplant or HSC gene therapy (HSC-GT). However, autoimmune complications and autoantibody production, including anti-nuclear antibodies (ANAs), frequently occur in ADA-SCID patients after treatment. To assess whether ADA deficiency affects the establishment of B cell tolerance, we tested the reactivity of recombinant antibodies isolated from single B cells of ADA-SCID patients before and after HSC-GT. We found that before HSC-GT, new emigrant/transitional and mature naive B cells from ADA-SCID patients contained more autoreactive and ANA-expressing clones, indicative of defective central and peripheral B cell tolerance checkpoints. We further observed impaired B cell receptor (BCR) and TLR functions in B cells after ADA inhibition, which may underlie the defects in B cell tolerance. Strikingly, after HSC-GT, ADA-SCID patients displayed quasi-normal early B cell tolerance checkpoints, as evidenced by restored removal of developing autoreactive and ANA-expressing B cells. Hence, ADA plays an essential role in controlling autoreactive B cell counterselection by regulating BCR and TLR functions. PMID:22622038

  13. Direct-to-Consumer Genetic Testing and Personal Genomics Services: A Review of Recent Empirical Studies

    PubMed Central

    Ostergren, Jenny

    2013-01-01

    Direct-to-consumer genetic testing (DTC-GT) has sparked much controversy and undergone dramatic changes in its brief history. Debates over appropriate health policies regarding DTC-GT would benefit from empirical research on its benefits, harms, and limitations. We review the recent literature (2011-present) and summarize findings across (1) content analyses of DTC-GT websites, (2) studies of consumer perspectives and experiences, and (3) surveys of relevant health care providers. Findings suggest that neither the health benefits envisioned by DTC-GT proponents (e.g., significant improvements in positive health behaviors) nor the worst fears expressed by its critics (e.g., catastrophic psychological distress and misunderstanding of test results, undue burden on the health care system) have materialized to date. However, research in this area is in its early stages and possesses numerous key limitations. We note needs for future studies to illuminate the impact of DTC-GT and thereby guide practice and policy regarding this rapidly evolving approach to personal genomics. PMID:24058877

  14. A gene cassette for adapting Escherichia coli strains as hosts for att-Int-mediated rearrangement and pL expression vectors.

    PubMed

    Balakrishnan, R; Bolten, B; Backman, K C

    1994-01-28

    A cassette of genes from bacteriophage lambda, when carried on a derivative of bacteriophage Mu, renders strains of Escherichia coli (and in principle other Mu-sensitive bacteria) capable of supporting lambda-based expression vectors, such as rearrangement vectors and pL vectors. The gene cassette contains a temperature-sensitive allele of the repressor gene, cIts857, and a shortened leftward operon comprising, oLpL, N, xis and int. Transfection and lysogenization of this cassette into various host bacteria is mediated by phage Mu functions. Examples of regulated expression of the gene encoding T4 DNA ligase are presented.

  15. Multi-color lightcurve observation of the asteroid (163249) 2002 GT

    NASA Astrophysics Data System (ADS)

    Oshima, M.; Abe, S.

    2014-07-01

    NASA's Deep Impact/EPOXI spacecraft plans to encounter the asteroid (163249) 2002 GT, classified as a PHA (Potentially Hazardous Asteroid), on January 4, 2020. However, the taxonomic type and spin state of 2002 GT remain to be determined. We have carried out ground-based multi-color (B-V-R-I) lightcurve observations taking advantage of the 2002 GT Characterization Campaign by NASA. Multi-color lightcurve measurements allow us to estimate the rotation period and obtain strong constraints on the shape and pole orientation. Here we found that the rotation period of 2002 GT is estimated to be 3.7248 ± 0.1664 h. In mid-2013, 2002 GT passed at 0.015 au from the Earth, resulting an exceptional opportunity for ground-based characterization. Using the 0.81-m telescope of the Tenagra Observatory (110°52'44.8''W, +31°27'44.4''N, 1312 m) in Arizona, USA, and the Johnson-Cousins BVRI filters, we have found lightcurves of 2002 GT (Figure). The Tenagra II 0.81-m telescope is used for research of the Hayabusa2 target Asteroid (162173) 1999 JU_3. The lightcurves (relative magnitude) show that the rotation period of 2002 GT, the target of NASA's Deep Impact/EPOXI spacecraft, is estimated to be 3.7248 ± 0.1664 hr. On June 9, 2013, we had 7 hours of ground-based observations on 2002 GT from 4:00 to 11:00 UTC. The number of comparison stars for differential photometry was 34. Because of tracking the fast-moving asteroid, it was necessary to have the same comparison star among the fields of vision. We have also obtained absolute photometry of 2002 GT on June 13, 2013.

  16. Effect of force tightening on cable tension and displacement in greater trochanter reattachment.

    PubMed

    Canet, Fanny; Duke, Kajsa; Bourgeois, Yan; Laflamme, G-Yves; Brailovski, Vladimir; Petit, Yvan

    2011-01-01

    The purpose of this study was to evaluate cable tension during installation, and during loading similar to walking in a cable grip type greater trochanter (GT), reattachment system. A 4th generation Sawbones composite femur with osteotomised GT was reattached with four Cable-Ready® systems (Zimmer, Warsaw, IN). Cables were tightened at 3 different target installation forces (178, 356 and 534 N) and retightened once as recommended by the manufacturer. Cables tension was continuously monitored using in-situ load cells. To simulate walking, a custom frame was used to apply quasi static load on the head of a femoral stem implant (2340 N) and abductor pull (667 N) on the GT. GT displacement (gap and sliding) relative to the femur was measured using a 3D camera system. During installation, a drop in cable tension was observed when tightening subsequent cables: an average 40+12.2% and 11 ± 5.9% tension loss was measured in the first and second cable. Therefore, retightening the cables, as recommended by the manufacturer, is important. During simulated walking, the second cable additionally lost up to 12.2+3.6% of tension. No difference was observed between the GT-femur gaps measured with cables tightened at different installation forces (p=0.32). The GT sliding however was significantly greater (0.9 ± 0.3 mm) when target installation force was set to only 178 N compared to 356 N (0.2 ± 0.1 mm); p<0.001. There were no significant changes when initial tightening force was increased to 534 N (0.3 ± 0.1 mm); p=0.11. In conclusion, the cable tightening force should be as close as possible to that recommended by the manufacturer, because reducing it compromises the stability of the GT fragment, whereas increasing it does not improve this stability, but could lead to cable breakage.

  17. Enhanced osteogenic differentiation of MC3T3-E1 cells on grid-topographic surface and evidence for involvement of YAP mediator.

    PubMed

    Zhang, Yingying; Gong, He; Sun, Yan; Huang, Yan; Fan, Yubo

    2016-05-01

    Numerous studies have shown that surface topography can promote cell-substrate associations and deeply influence cell fate. The intracellular mechanism or how micro- or nano-patterned extracellular signal is ultimately linked to activity of nuclear transcription factors remains unknown. It has been reported that Yes-associated protein (YAP) can respond to extracellular matrix microenvironment signals, thus regulates stem cell differentiation process. We propose that YAP may play a role in mediating the topography induced cell differentiation. To this end, we fabricated polydimethylsiloxane (PDMS) micropatterns with grid topology (GT) (3 μm pattern width, 2 μm pattern interval length, 7 μm pattern height); nonpatterned PDMS substrates were used as the planar controls. The MC3T3-E1 cells were then cultured on these surfaces, respectively, in osteogenic inducing medium. Cell differentiation in terms of osteogenesis related gene expression, protein levels, alkaline phosphatase activity and extracellular matrix mineralization was assessed. It was shown that the cells on GT surfaces had stronger osteogenesis capacity. In addition, expression level of YAP was increased when MC3T3-E1 cells grew on GT substrates, which was similar to the levels of osteogenic differentiation markers. It was also shown that YAP knockdown attenuated GT substrates-induced MC3T3-E1 differentiation, which reduced the osteogenic differentiation effect of the GT substrates. Collectively, our findings indicate that GT substrates-induced MC3T3-E1 differentiation may be associated with YAP. This paper provides new target points for transcriptional mechanism research of microenvironment induced cell differentiation and a useful approach to obtain more biofunctionalization scaffolds for tissue engineering. © 2016 Wiley Periodicals, Inc.

  18. Peginterferon lambda for the treatment of HBeAg-positive chronic hepatitis B: A randomized phase 2b study (LIRA-B).

    PubMed

    Chan, Henry L Y; Ahn, Sang Hoon; Chang, Ting-Tsung; Peng, Cheng-Yuan; Wong, David; Coffin, Carla S; Lim, Seng Gee; Chen, Pei-Jer; Janssen, Harry L A; Marcellin, Patrick; Serfaty, Lawrence; Zeuzem, Stefan; Cohen, David; Critelli, Linda; Xu, Dong; Wind-Rotolo, Megan; Cooney, Elizabeth

    2016-05-01

    Peginterferon lambda-1a (lambda) is a Type-III interferon, which, like alfa interferons, has antiviral activity in vitro against hepatitis B virus (HBV) and hepatitis C virus (HCV); however, lambda has a more limited extra-hepatic receptor distribution. This phase 2b study (LIRA-B) evaluated lambda in patients with chronic HBV infection. Adult HBeAg+ interferon-naive patients were randomized (1:1) to weekly lambda (180 μg) or peginterferon alfa-2a (alfa) for 48 weeks. The primary efficacy endpoint was HBeAg seroconversion at week 24 post-treatment; lambda non-inferiority was demonstrated if the 80% confidence interval (80% CI) lower bound was >-15%. Baseline characteristics were balanced across groups (lambda N=80; alfa N=83). Early on-treatment declines in HBV-DNA and qHBsAg through week 24 were greater with lambda. HBeAg seroconversion rates were comparable for lambda and alfa at week 48 (17.5% vs. 16.9%, respectively); however lambda non-inferiority was not met at week 24 post-treatment (13.8% vs. 30.1%, respectively; lambda vs. alfa 80% CI lower bound -24%). Results for other key secondary endpoints (virologic, serologic, biochemical) and post hoc combined endpoints (HBV-DNA <2000 IU/ml plus HBeAg seroconversion or ALT normalization) mostly favored alfa. Overall adverse events (AE), serious AE, and AE-discontinuation rates were comparable between arms but AE-spectra differed (more cytopenias, flu-like, and musculoskeletal symptoms observed with alfa, more ALT flares and bilirubin elevations seen with lambda). Most on-treatment flares occurred early (weeks 4-12), associated with HBV-DNA decline; all post-treatment flares were preceded by HBV-DNA rise. On-treatment, lambda showed greater early effects on HBV-DNA and qHBsAg, and comparable serologic/virologic responses at end-of-treatment. However, post-treatment, alfa-associated HBeAg seroconversion rates were higher, and key secondary results mostly favored alfa. ClinicalTrials.gov number: NCT01204762. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  19. Variable phenotypic expression and onset in MYH14 distal hereditary motor neuropathy phenotype in a large, multigenerational North American family.

    PubMed

    Iyadurai, Stanley; Arnold, W David; Kissel, John T; Ruhno, Corey; Mcgovern, Vicki L; Snyder, Pamela J; Prior, Thomas W; Roggenbuck, Jennifer; Burghes, Arthur H; Kolb, Stephen J

    2017-08-01

    Distal hereditary motor neuropathy (dHMN) causes distal-predominant weakness without prominent sensory loss. Myosin heavy chain disorders most commonly result in distal myopathy and cardiomyopathy with or without hearing loss, but a complex phenotype with dHMN, myopathy, hoarseness, and hearing loss was reported in a Korean family with a c.2822G>T mutation in MYH14. In this study we report phenotypic features in a North American family with the c.2822G>T in MYH14. Clinical and molecular characterization was performed in a large, 6-generation, Caucasian family with MYH14 dHMN. A total of 11 affected and 7 unaffected individuals were evaluated and showed varying age of onset and severity of weakness. Genotypic concordance was confirmed with molecular analysis. Electrophysiological studies demonstrated distal motor axonal degeneration without myopathy in all affected subjects tested. Mutation of MYH14 can result in a range of neuromuscular phenotypes that includes a dHMN and hearing loss phenotype with variable age of onset. Muscle Nerve 56: 341-345, 2017. © 2016 Wiley Periodicals, Inc.

  20. Chimeric Lyssavirus Glycoproteins with Increased Immunological Potential

    PubMed Central

    Jallet, Corinne; Jacob, Yves; Bahloul, Chokri; Drings, Astrid; Desmezieres, Emmanuel; Tordo, Noël; Perrin, Pierre

    1999-01-01

    The rabies virus glycoprotein molecule (G) can be divided into two parts separated by a flexible hinge: the NH2 half (site II part) containing antigenic site II up to the linear region (amino acids [aa] 253 to 275 encompassing epitope VI [aa 264]) and the COOH half (site III part) containing antigenic site III and the transmembrane and cytoplasmic domains. The structural and immunological roles of each part were investigated by cell transfection and mouse DNA-based immunization with homogeneous and chimeric G genes formed by fusion of the site II part of one genotype (GT) with the site III part of the same or another GT. Various site II-site III combinations between G genes of PV (Pasteur virus strain) rabies (GT1), Mokola (GT3), and EBL1 (European bat lyssavirus 1 [GT5]) viruses were tested. Plasmids pGPV-PV, pGMok-Mok, pGMok-PV, and pGEBL1-PV induced transient expression of correctly transported and folded antigens in neuroblastoma cells and virus-neutralizing antibodies against parental viruses in mice, whereas, pG-PVIII (site III part only) and pGPV-Mok did not. The site III part of PV (GT1) was a strong inducer of T helper cells and was very effective at presenting the site II part of various GTs. Both parts are required for correct folding and transport of chimeric G proteins which have a strong potential value for immunological studies and development of multivalent vaccines. Chimeric plasmid pGEBL1-PV broadens the spectrum of protection against European lyssavirus genotypes (GT1, GT5, and GT6). PMID:9847325

  1. Alkaline Ceramidase 2 (ACER2) and Its Product Dihydrosphingosine Mediate the Cytotoxicity of N-(4-Hydroxyphenyl)retinamide in Tumor Cells*

    PubMed Central

    Mao, Zhehao; Sun, Wei; Xu, Ruijuan; Novgorodov, Sergei; Szulc, Zdzislaw M.; Bielawski, Jacek; Obeid, Lina M.; Mao, Cungui

    2010-01-01

    Increased generation of dihydrosphingosine (DHS), a bioactive sphingolipid, has been implicated in the cytotoxicity of the synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) in tumor cells. However, how 4-HPR increases DHS remains unclear. Here we demonstrate that 4-HPR increases the expression of ACER2, which catalyzes the hydrolysis of dihydroceramides to generate DHS, and that ACER2 up-regulation plays a key role in mediating the 4-HPR-induced generation of DHS as well as the cytotoxicity of 4-HPR in tumor cells. Treatment with 4-HPR induced the accumulation of dihydroceramides (DHCs) in tumor cells by inhibiting dihydroceramide desaturase (DES) activity, which catalyzes the conversion of DHCs to ceramides. Treatment with 4-HPR also increased ACER2 expression through a retinoic acid receptor-independent and caspase-dependent manner. Overexpression of ACER2 augmented the 4-HPR-induced generation of DHS as well as 4-HPR cytotoxicity, and 4-HPR-induced death in tumor cells, whereas knocking down ACER2 had the opposite effects. ACER2 overexpression, along with treatment with GT11, another DES inhibitor, markedly increased cellular DHS, leading to tumor cell death, whereas ACER2 overexpression or GT11 treatment alone failed to do so, suggesting that both ACER2 up-regulation and DES inhibition are necessary and sufficient to mediate 4-HPR-induced DHS accumulation, cytotoxicity, and death in tumor cells. Taken together, these results suggest that up-regulation of the ACER2/DHS pathway mediates the cytotoxicity of 4-HPR in tumor cells and that up-regulating or activating ACER2 may improve the anti-cancer activity of 4-HRR and other DHC-inducing agents. PMID:20628055

  2. Disrupted SOX10 function causes spongiform neurodegeneration in gray tremor mice

    PubMed Central

    Anderson, Sarah R.; Lee, Inyoul; Ebeling, Christine; Stephenson, Dennis A.; Schweitzer, Kelsey M.; Baxter, David; Moon, Tara M.; LaPierre, Sarah; Jaques, Benjamin; Silvius, Derek; Wegner, Michael; Hood, Leroy E.; Carlson, George; Gunn, Teresa M.

    2014-01-01

    Mice homozygous for the gray tremor (gt) mutation have a pleiotropic phenotype that includes pigmentation defects, megacolon, whole body tremors, sporadic seizures, hypo- and dysmyelination of the CNS and PNS, vacuolation of the CNS, and early death. Vacuolation similar to that caused by prions was originally reported to be transmissible, but subsequent studies showed the inherited disease was not infectious. The gt mutation mapped to distal mouse chromosome 15, to the same region as Sox10, which encodes a transcription factor with essential roles in neural crest survival and differentiation. As dominant mutations in mouse or human SOX10 cause white spotting and intestinal aganglionosis, we screened the Sox10 coding region for mutations in gt/gt DNA. An adenosine to guanine transversion was identified in exon 2 that changes a highly conserved glutamic acid residue in the SOX10 DNA binding domain to glycine. This mutant allele was not seen in wildtype mice, including the related GT/Le strain, and failed to complement a Sox10 null allele. Gene expression analysis revealed significant down-regulation of genes involved in myelin lipid biosynthesis pathways in gt/gt brains. Knockout mice for some of these genes develop CNS vacuolation and/or myelination defects, suggesting that their down-regulation may contribute to these phenotypes in gt mutants and could underlie the neurological phenotypes associated with Peripheral demyelinating neuropathy-Central dysmyelinating leukodystrophy-Waardenburg syndrome-Hirschsprung (PCWH) disease, caused by mutations in human SOX10. PMID:25399070

  3. PWA prospects for K+Lambda and K+Sigma^0 photoproduction

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

    Biplab Dey, Michael E. McCracken, Curtis A. Meyer

    2012-04-01

    We present a status update on the CMU group PWA efforts in the strangeness (K{sup +}{Lambda}/K{sup +}{Sigma}{sup 0}) sector. The bulk of the currently available data comes from recently published CLAS g11a results, with extensive polarization data expected soon from the CLAS g8 and g9 set of experiments. We give a brief description of issues pertaining to different sign conventions for the polarization observables in the literature, and normalization discrepancies between the CLAS-g11a results and older high energy data from SLAC/CEA/DESY that used an untagged photon beam.

  4. Investigations of potential bias in the estimation of lambda using Pradel's (1996) model for capture-recapture data

    USGS Publications Warehouse

    Hines, J.E.; Nichols, J.D.

    2002-01-01

    Pradel's (1996) temporal symmetry model permitting direct estimation and modelling of population growth rate, lambda sub i provides a potentially useful tool for the study of population dynamics using marked animals. Because of its recent publication date, the approach has not seen much use, and there have been virtually no investigations directed at robustness of the resulting estimators. Here we consider several potential sources of bias, all motivated by specific uses of this estimation approach. We consider sampling situations in which the study area expands with time and present an analytic expression for the bias in lambda hat sub i. We next consider trap response in capture probabilities and heterogeneous capture probabilities and compute large-sample and simulation-based approximations of resulting bias in lambda hat sub i. These approximations indicate that trap response is an especially important assumption violation that can produce substantial bias. Finally, we consider losses on capture and emphasize the importance of selecting the estimator for lambda sub i that is appropriate to the question being addressed. For studies based on only sighting and resighting data, Pradel's (1996) lambda hat prime sub i is the appropriate estimator.

  5. Characterization of a lambda-cyhalothrin metabolizing glutathione S-transferase CpGSTd1 from Cydia pomonella (L.).

    PubMed

    Liu, Jiyuan; Yang, Xueqing; Zhang, Yalin

    2014-11-01

    In insects, glutathione S-transferases (GSTs) are enzymes involved in detoxification of insecticides. However, few data are available for the codling moth, Cydia pomonella (L.). In this study, we cloned a delta class GST gene CpGSTd1 from C. pomonella. Real-time quantitative PCR shows that CpGSTd1 was up-regulated with aging, and the mRNA level of CpGSTd1 was higher in the fat body and silk glands than in other tissues. The expression level of CpGSTd1 exposure to insecticide suggests that CpGSTd1 is up-regulated after chlorpyrifos-methyl and lambda-cyhalothrin treatments. Both lambda-cyhalothrin and chlorpyrifos-methyl altered GST activity in vivo. The purified CpGSTd1 protein exhibits a high catalytic efficiency with CDNB and was inhibited by lambda-cyhalothrin and chlorpyrifos-methyl in vitro. Metabolism assays indicate that lambda-cyhalothrin was significantly metabolized while chlorpyrifos-methyl was not metabolized by CpGSTd1. Binding free energy analysis suggests that CpGSTd1 binding is tighter with lambda-cyhalothrin than with chlorpyrifos-methyl. Our study suggests that CpGSTd1 plays a key role in the metabolism of insecticides in C. pomonella.

  6. Transcription attenuation is the major mechanism by which the leu operon of Salmonella typhimurium is controlled.

    PubMed

    Searles, L L; Wessler, S R; Calvo, J M

    1983-01-25

    Three mutations, each causing constitutive expression of the Salmonella typhimurium leu operon, were cloned into phage vector lambda gt4 on EcoRI DNA fragments carrying all of that operon except for part of the promoter-distal last gene. Sequence analysis of DNA from these phage demonstrated that each contains a single base change in the leu attenuator. Transcription of mutant DNA in vitro resulted in transcription beyond the usual site of termination. The level of beta-IPM dehydrogenase, the leuB enzyme, was elevated 40-fold in a strain carrying one of these mutations, and starvation of this strain for leucine had little effect on the amount of activity expressed. Using a strain with a wild-type promoter-leader region of the leu operon, the rates of synthesis and degradation of leu leader RNA and readthrough RNA (leu mRNA) were measured by DNA-RNA hybridizations with specific DNA probes. The rate of synthesis of the leu leader was about the same in cells grown with excess or with limiting leucine. On the other hand, the rate of synthesis of leu mRNA was 12-fold higher for cells grown in limiting leucine as opposed to excess leucine. The rate of degradation of these RNA species was the same under both conditions of growth. Thus, the variation in expression of the leu operon observed for cells grown in minimal medium is, for the most part, not caused by control over the frequency of initiation or by the differential stability of these RNA species. Rather, the variation is a direct result of the frequency of transcription termination at an attenuator site. These results taken together suggest that transcription attenuation is the major mechanism by which leucine regulates expression of the leu operon of S. typhimurium for cells growing in a minimal medium.

  7. The effect of Aspergillus fumigatus infection on vitamin D receptor expression in cystic fibrosis.

    PubMed

    Coughlan, Catherine A; Chotirmall, Sanjay H; Renwick, Julie; Hassan, Tidi; Low, Teck Boon; Bergsson, Gudmundur; Eshwika, Ahmed; Bennett, Kathleen; Dunne, Katie; Greene, Catherine M; Gunaratnam, Cedric; Kavanagh, Kevin; Logan, Patrick M; Murphy, Philip; Reeves, Emer P; McElvaney, Noel G

    2012-11-15

    Aspergillus fumigatus (A. fumigatus) in cystic fibrosis (CF) is increasingly recognized. Although allergic bronchopulmonary aspergillosis (ABPA) leads to deterioration of pulmonary function, the effect of A. fumigatus colonization in the absence of ABPA remains unclear. To address this, we examined individuals with CF with A. fumigatus who were ABPA negative to identify the effects of itraconazole therapy on Aspergillus-induced lung inflammation. The effect of A. fumigatus on nuclear vitamin D receptor (VDR) expression was investigated using qRT-PCR and Western blotting. IL-5 and IL-13 levels were quantified by ELISA. The effect of itraconazole was assessed by a combination of high-resolution computed tomography, lung function test, and microbiological analysis. We demonstrate that A. fumigatus down-regulates VDR in macrophages and airway epithelial cells and that the fungal metabolite gliotoxin (Gt) is the main causative agent. Gt overcame the positive effect of 1,25-OH vitamin D(3) on VDR expression in vitro, resulting in increased IL-5 and IL-13 production. In vivo, A. fumigatus positivity was associated with increased Gt in CF bronchoalveolar lavage fluid and increased bronchoalveolar lavage fluid levels of IL-5 and IL-13. After airway eradication of A. fumigatus with itraconazole, we observed decreased Gt, IL-5 and IL-13, improved respiratory symptoms, and diminished high-resolution computed tomography mosaic pattern consistent with sustained pulmonary function. This study provides a rationale for the therapeutic effect of itraconazole and implied that the therapeutic potential of vitamin D supplementation in preventing ABPA is only feasible with concurrent elimination of A. fumigatus to permit VDR expression and its positive functional consequences.

  8. Tertiary structure of human {Lambda}6 light chains.

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

    Pokkuluri, P. R.; Solomon, A.; Weiss, D. T.

    1999-01-01

    AL amyloidosis is a disease process characterized by the pathologic deposition of monoclonal light chains in tissue. To date, only limited information has been obtained on the molecular features that render such light chains amyloidogenic. Although protein products of the major human V kappa and V lambda gene families have been identified in AL deposits, one particular subgroup--lambda 6--has been found to be preferentially associated with this disease. Notably, the variable region of lambda 6 proteins (V lambda 6) has distinctive primary structural features including the presence in the third framework region (FR3) of two additional amino acid residues thatmore » distinguish members of this subgroup from other types of light chains. However, the structural consequences of these alterations have not been elucidated. To determine if lambda 6 proteins possess unique tertiary structural features, as compared to light chains of other V lambda subgroups, we have obtained x-ray diffraction data on crystals prepared from two recombinant V lambda 6 molecules. These components, isolated from a bacterial expression system, were generated from lambda 6-related cDNAs cloned from bone marrow-derived plasma cells from a patient (Wil) who had documented AL amyloidosis and another (Jto) with multiple myeloma and tubular cast nephropathy, but no evident fibrillar deposits. The x-ray crystallographic analyses revealed that the two-residue insertion located between positions 68 and 69 (not between 66 and 67 as previously surmised) extended an existing loop region that effectively increased the surface area adjacent to the first complementarity determining region (CDR1). Further, an unusual interaction between the Arg 25 and Phe 2 residues commonly found in lambda 6 molecules was noted. However, the structures of V lambda 6 Wil and Jto also differed from each other, as evidenced by the presence in the latter of certain ionic and hydrophobic interactions that we posit increased protein stability and thus prevented amyloid formation.« less

  9. Genetically Modified Flax Expressing NAP-SsGT1 Transgene: Examination of Anti-Inflammatory Action

    PubMed Central

    Matusiewicz, Magdalena; Kosieradzka, Iwona; Zuk, Magdalena; Szopa, Jan

    2014-01-01

    The aim of the work was to define the influence of dietary supplementation with GM (genetically modified) GT#4 flaxseed cake enriched in polyphenols on inflammation development in mice liver. Mice were given ad libitum isoprotein diets: (1) standard diet; (2) high-fat diet rich in lard, high-fat diet enriched with 30% of (3) isogenic flax Linola seed cake; and (4) GM GT#4 flaxseed cake; for 96 days. Administration of transgenic and isogenic seed cake lowered body weight gain, of transgenic to the standard diet level. Serum total antioxidant status was statistically significantly improved in GT#4 flaxseed cake group and did not differ from Linola. Serum thiobarbituric acid reactive substances, lipid profile and the liver concentration of pro-inflammatory cytokine tumor necrosis factor-α were ameliorated by GM and isogenic flaxseed cake consumption. The level of pro-inflammatory cytokine interferon-γ did not differ between mice obtaining GM GT#4 and non-GM flaxseed cakes. The C-reactive protein concentration was reduced in animals fed GT#4 flaxseed cake and did not differ from those fed non-GM flaxseed cake-based diet. Similarly, the liver structure of mice consuming diets enriched in flaxseed cake was improved. Dietetic enrichment with GM GT#4 and non-GM flaxseed cakes may be a promising solution for health problems resulting from improper diet. PMID:25247574

  10. Monoterpenyl Glycosyltransferases Differentially Contribute to Production of Monoterpenyl Glycosides in Two Aromatic Vitis vinifera Varieties

    PubMed Central

    Li, Xiang-Yi; Wen, Ya-Qin; Meng, Nan; Qian, Xu; Pan, Qiu-Hong

    2017-01-01

    HIGHLIGHTS A similar trend on accumulation of glycosidically bound monoterpenes was observed in both varietiesTwo VvGT7 alleles mutations occurred at key sites in Muscat blanc à PetitVvGT14 exerted a major role in production of monoterpenyl glycosides in both varieties Terpenoids are the major aroma components and generally exist as both free and glycosidically-bound forms, of which nonvolatile glycosides account for a large fraction in grape berries. Our previous study has indicated that differential accumulation of monoterpenyl glycosides in Vitis vinifera “Muscat blanc à Petit” between two regions is closely correlated to monoterpenyl glucosyltransferase (VvGT14, XM_002285734.2) transcript abundance. However, it has not been determined yet whether this correlation also exists in other Vitis vinifera varieties. This study investigated the evolution of free and glycosidically bound monoterpenes in two Vitis vinifera variety “Muscat blanc à Petit” and “Gewurztraminer” under two vintages, and further assessed the relation between the accumulation of bound monoterpenes and two monoterpenyl glycosyltransferase transcript levels. Results showed that free monoterpenes exhibited three evolution patterns in both varieties during berry development of two vintages, whereas glycosidically bound monoterpenes showed a concentration elevation with berry maturation. The Cis-rose oxide and geraniol were major components contributing to the aroma odors of “Gewürztraminer” grapes while linalool was major aroma contributor to the “Muscat blanc à Petit grain” grapes. The accumulation of glycosidically bound monoterpenes in both varieties was accompanied with the high expression of VvGT7 (XM_002276510.2) and VvGT14. Only one allele of VvGT7 was found in the variety “Gewürztraminer” and no mutation was observed in its enzyme active sites. XB-VvGT7-4 and XB-VvGT7-5 were two alleles of VvGT7 detected in “Muscat blanc à Petit grain.” The mutation on its enzyme active site inhibited the activity of XB-VvGT7-4, whereas VvGT7-5 exhibited an alteration on enzyme activity due to the insertion mutation at the position 443. Only one VvGT14 allele was found in both varieties, and the VvGT14 allele in both varieties showed the similarity on amino acid sequence. No mutation occurred in active sites of VvGT14 allele. These indicated that VvGT7 and VvGT14 differentially contributed to the production of monoterpenyl glycosides in these Vitis Vinifera varieties. PMID:28751905

  11. Monoterpenyl Glycosyltransferases Differentially Contribute to Production of Monoterpenyl Glycosides in Two Aromatic Vitis vinifera Varieties.

    PubMed

    Li, Xiang-Yi; Wen, Ya-Qin; Meng, Nan; Qian, Xu; Pan, Qiu-Hong

    2017-01-01

    HIGHLIGHTS A similar trend on accumulation of glycosidically bound monoterpenes was observed in both varietiesTwo VvGT7 alleles mutations occurred at key sites in Muscat blanc à Petit VvGT14 exerted a major role in production of monoterpenyl glycosides in both varieties Terpenoids are the major aroma components and generally exist as both free and glycosidically-bound forms, of which nonvolatile glycosides account for a large fraction in grape berries. Our previous study has indicated that differential accumulation of monoterpenyl glycosides in Vitis vinifera "Muscat blanc à Petit" between two regions is closely correlated to monoterpenyl glucosyltransferase ( VvGT14 , XM_002285734.2) transcript abundance. However, it has not been determined yet whether this correlation also exists in other Vitis vinifera varieties. This study investigated the evolution of free and glycosidically bound monoterpenes in two Vitis vinifera variety "Muscat blanc à Petit" and "Gewurztraminer" under two vintages, and further assessed the relation between the accumulation of bound monoterpenes and two monoterpenyl glycosyltransferase transcript levels. Results showed that free monoterpenes exhibited three evolution patterns in both varieties during berry development of two vintages, whereas glycosidically bound monoterpenes showed a concentration elevation with berry maturation. The Cis -rose oxide and geraniol were major components contributing to the aroma odors of "Gewürztraminer" grapes while linalool was major aroma contributor to the "Muscat blanc à Petit grain" grapes. The accumulation of glycosidically bound monoterpenes in both varieties was accompanied with the high expression of VvGT7 (XM_002276510.2) and VvGT14 . Only one allele of VvGT7 was found in the variety "Gewürztraminer" and no mutation was observed in its enzyme active sites. XB-VvGT7-4 and XB-VvGT7-5 were two alleles of VvGT7 detected in "Muscat blanc à Petit grain." The mutation on its enzyme active site inhibited the activity of XB-VvGT7-4 , whereas VvGT7-5 exhibited an alteration on enzyme activity due to the insertion mutation at the position 443. Only one VvGT14 allele was found in both varieties, and the VvGT14 allele in both varieties showed the similarity on amino acid sequence. No mutation occurred in active sites of VvGT14 allele. These indicated that VvGT7 and VvGT14 differentially contributed to the production of monoterpenyl glycosides in these Vitis Vinifera varieties.

  12. Gum tragacanth/poly(l-lactic acid) nanofibrous scaffolds for application in regeneration of peripheral nerve damage.

    PubMed

    Ranjbar-Mohammadi, Marziyeh; Prabhakaran, Molamma P; Bahrami, S Hajir; Ramakrishna, Seeram

    2016-04-20

    Nanofibrous nerve guides have gained huge interest in supporting the peripheral nerve regeneration due to their abilities to simulate the topography, mechanical, biological and extracellular matrix morphology of native tissue. Gum tragacanth (GT) is a biocompatible mixture of polysaccharides that has been used in biomedical applications. During this study, we fabricated aligned and random nanofibers from poly(l-lactic acid) and gum tragacanth (PLLA/GT) in various ratios (100:0, 75:25, and 50:50) by electrospinning. Scanning electron microscope demonstrated smooth and uniform nanofibers with diameters in the range of 733±65nm and 226±73nm for align PLLA and random PLLA/GT 50:50 nanofibers, respectively. FTIR analysis, contact angle, in vitro biodegradation and tensile measurements were carried out to evaluate the chemical and mechanical properties of the different scaffolds. PLLA/GT 75:25 exhibited the most balanced properties compared to other scaffolds and was used for in vitro culture of nerve cells (PC12) to assess the potential of using these scaffolds as a substrate for nerve regeneration. The cells were found to attach and proliferate on aligned PLLA/GT 75:25 scaffolds, expressing bi-polar neurite extensions and the orientation of nerve cells was along the direction of the fiber alignment. Results of 8 days of in vitro culture of PC12 cells on aligned PLLA/GT 75:25 nanofibers, showed 20% increase in cell proliferation compared to PLLA/GT 75:25 random nanofibers. PLLA/GT 75:25 aligned nanofibers acted as a favorable cue to support neurite outgrowth and nerve cell elongation compared with PLLA nanofibers. Our results showed that aligned PLLA/GT 75:25 nanofibers are promising substrates for application as bioengineered grafts for nerve tissue regeneration. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Global carbon budget 2013

    NASA Astrophysics Data System (ADS)

    Le Quéré, C.; Peters, G. P.; Andres, R. J.; Andrew, R. M.; Boden, T.; Ciais, P.; Friedlingstein, P.; Houghton, R. A.; Marland, G.; Moriarty, R.; Sitch, S.; Tans, P.; Arneth, A.; Arvanitis, A.; Bakker, D. C. E.; Bopp, L.; Canadell, J. G.; Chini, L. P.; Doney, S. C.; Harper, A.; Harris, I.; House, J. I.; Jain, A. K.; Jones, S. D.; Kato, E.; Keeling, R. F.; Klein Goldewijk, K.; Körtzinger, A.; Koven, C.; Lefèvre, N.; Omar, A.; Ono, T.; Park, G.-H.; Pfeil, B.; Poulter, B.; Raupach, M. R.; Regnier, P.; Rödenbeck, C.; Saito, S.; Schwinger, J.; Segschneider, J.; Stocker, B. D.; Tilbrook, B.; van Heuven, S.; Viovy, N.; Wanninkhof, R.; Wiltshire, A.; Zaehle, S.; Yue, C.

    2013-11-01

    Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe datasets and a methodology to quantify all major components of the global carbon budget, including their uncertainties, based on the combination of a range of data, algorithms, statistics and model estimates and their interpretation by a broad scientific community. We discuss changes compared to previous estimates consistency within and among components, alongside methodology and data limitations. CO2 emissions from fossil-fuel combustion and cement production (EFF) are based on energy statistics, while emissions from Land-Use Change (ELUC), including deforestation, are based on combined evidence from land-cover change data, fire activity in regions undergoing deforestation, and models. The global atmospheric CO2 concentration is measured directly and its rate of growth (GATM) is computed from the annual changes in concentration. The mean ocean CO2 sink (SOCEAN) is based on observations from the 1990s, while the annual anomalies and trends are estimated with ocean models. The variability in SOCEAN is evaluated for the first time in this budget with data products based on surveys of ocean CO2 measurements. The global residual terrestrial CO2 sink (SLAND) is estimated by the difference of the other terms of the global carbon budget and compared to results of Dynamic Global Vegetation Models. All uncertainties are reported as ± 1 sigma, reflecting the current capacity to characterise the annual estimates of each component of the global carbon budget. For the last decade available (2003-2012), EFF was 8.6 ± 0.4 GtC yr-1, ELUC 0.8 ± 0.5 GtC yr-1, GATM 4.3 ± 0.1 GtC yr-1, SOCEAN 2.6 ± 0.5 GtC yr-1, and SLAND 2.6 ± 0.8 GtC yr-1. For year 2012 alone, EFF grew to 9.7 ± 0.5 GtC yr-1, 2.2% above 2011, reflecting a continued trend in these emissions; GATM was 5.2 ± 0.2 GtC yr-1, SOCEAN was 2.9 ± 0.5 GtC yr-1, and assuming and ELUC of 0.9 ± 0.5 GtC yr-1 (based on 2001-2010 average), SLAND was 2.5 ± 0.9 GtC yr-1. GATM was high in 2012 compared to the 2003-2012 average, almost entirely reflecting the high EFF. The global atmospheric CO2 concentration reached 392.52 ± 0.10 ppm on average over 2012. We estimate that EFF will increase by 2.1% (1.1-3.1%) to 9.9 ± 0.5 GtC in 2013, 61% above emissions in 1990, based on projections of World Gross Domestic Product and recent changes in the carbon intensity of the economy. With this projection, cumulative emissions of CO2 will reach about 550 ± 60 GtC for 1870-2013, 70% from EFF (390 ± 20 GtC) and 30% from ELUC (160 ± 55 GtC). This paper is intended to provide a baseline to keep track of annual carbon budgets in the future. All data presented here can be downloaded from the Carbon Dioxide Information Analysis Center (10.3334/CDIAC/GCP_2013_v1.1).

  14. Seasonal flux and assemblage composition of planktic foraminifera from the northern Gulf of Mexico, 2008-11

    USGS Publications Warehouse

    Reynolds, Caitlin E.; Poore, Richard Z.

    2013-01-01

    The U.S. Geological Survey anchored a sediment trap in the northern Gulf of Mexico to collect seasonal time-series data on the flux and assemblage composition of live planktic foraminifers. This report provides an update of the previous time-series data to include results from 2011. Ten species, or varieties, constituted ~92 percent of the 2011 assemblage: Globigerinoides ruber (pink and white varieties), Globigerinoides sacculifer, Globigerina calida, Globigerinella aequilateralis, Globorotalia menardii group [The Gt. menardii group includes Gt. menardii, Gt. tumida, and Gt. ungulata], Orbulina universa, Globorotalia truncatulinoides, Pulleniatina spp., and Neogloboquadrina dutertrei. The mean daily flux was 205 tests per square meter per day (m-2 day-1), with maximum fluxes of >600 tests m-2 day-1 during mid-February and mid-September and minimum fluxes of -2 day-1 during mid-March, the beginning of May, and November. Globorotalia truncatulinoides showed a clear preference for the winter, consistent with data from 2008 to 2010. Globigerinoides ruber (white) flux data for 2011 (average 30 tests m-2 day-1) were consistent with data from 2010 (average 29 m-2 day-1) and showed a steady threefold increase since 2009 (average 11 tests m-2 day-1) and a tenfold increase from the 2008 flux (3 tests m-2 day-1).

  15. Expression, purification, crystallization and preliminary X-ray characterization of a putative glycosyltransferase of the GT-A fold found in mycobacteria

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

    Fulton, Zara; Crellin, Paul K.; Brammananth, Rajini

    2008-05-28

    Glycosidic bond formation is a ubiquitous enzyme-catalysed reaction. This glycosyltransferase-mediated process is responsible for the biosynthesis of innumerable oligosaccharides and glycoconjugates and is often organism- or cell-specific. However, despite the abundance of genomic information on glycosyltransferases (GTs), there is a lack of structural data for this versatile class of enzymes. Here, the cloning, expression, purification and crystallization of an essential 329-amino-acid (34.8 kDa) putative GT of the classic GT-A fold implicated in mycobacterial cell-wall biosynthesis are reported. Crystals of MAP2569c from Mycobacterium avium subsp. paratuberculosis were grown in 1.6 M monoammonium dihydrogen phosphate and 0.1 M sodium citrate pH 5.5.more » A complete data set was collected to 1.8 {angstrom} resolution using synchrotron radiation from a crystal belonging to space group P4{sub 1}2{sub 1}2.« less

  16. A chimeric α-amylase engineered from Bacillus acidicola and Geobacillus thermoleovorans with improved thermostability and catalytic efficiency.

    PubMed

    Parashar, Deepak; Satyanarayana, T

    2016-04-01

    The α-amylase (Ba-amy) of Bacillus acidicola was fused with DNA fragments encoding partial N- and C-terminal region of thermostable α-amylase gene of Geobacillus thermoleovorans (Gt-amy). The chimeric enzyme (Ba-Gt-amy) expressed in Escherichia coli displays marked increase in catalytic efficiency [K cat: 4 × 10(4) s(-1) and K cat/K m: 5 × 10(4) mL(-1) mg(-1) s(-1)] and higher thermostability than Ba-amy. The melting temperature (T m) of Ba-Gt-amy (73.8 °C) is also higher than Ba-amy (62 °C), and the CD spectrum analysis revealed the stability of the former, despite minor alteration in secondary structure. Langmuir-Hinshelwood kinetic analysis suggests that the adsorption of Ba-Gt-amy onto raw starch is more favourable than Ba-amy. Ba-Gt-amy is thus a suitable biocatalyst for raw starch saccharification at sub-gelatinization temperatures because of its acid stability, thermostability and Ca(2+) independence, and better than the other known bacterial acidic α-amylases.

  17. Subunit profiling and functional characteristics of acetylcholine receptors in GT1-7 cells.

    PubMed

    Arai, Yuki; Ishii, Hirotaka; Kobayashi, Makito; Ozawa, Hitoshi

    2017-03-01

    GnRH neurons form a final common pathway for the central regulation of reproduction. Although the involvement of acetylcholine in GnRH secretion has been reported, direct effects of acetylcholine and expression profiles of acetylcholine receptors (AChRs) still remain to be studied. Using immortalized GnRH neurons (GT1-7 cells), we analyzed molecular expression and functionality of AChRs. Expression of the mRNAs were identified in the order α7 > β2 = β1 ≧ α4 ≧ α5 = β4 = δ > α3 for nicotinic acetylcholine receptor (nAChR) subunits and m4 > m2 for muscarinic acetylcholine receptor (mAChR) subtypes. Furthermore, this study revealed that α7 nAChRs contributed to Ca 2+ influx and GnRH release and that m2 and m4 mAChRs inhibited forskolin-induced cAMP production and isobutylmethylxanthine-induced GnRH secretion. These findings demonstrate the molecular profiles of AChRs, which directly contribute to GnRH secretion in GT1-7 cells, and provide one possible regulatory action of acetylcholine in GnRH neurons.

  18. Expression, purification, crystallization and preliminary X-ray characterization of a putative glycosyltransferase of the GT-A fold found in mycobacteria

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

    Fulton, Zara; Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Monash University, Clayton, Victoria 3800; Crellin, Paul K.

    2008-05-01

    MAP2569c from M. avium subsp. paratuberculosis, a putative glycosyltransferase implicated in mycobacterial cell-wall biosynthesis, was cloned, expressed, purified and crystallized. X-ray diffraction data were collected to 1.8 Å resolution. Glycosidic bond formation is a ubiquitous enzyme-catalysed reaction. This glycosyltransferase-mediated process is responsible for the biosynthesis of innumerable oligosaccharides and glycoconjugates and is often organism- or cell-specific. However, despite the abundance of genomic information on glycosyltransferases (GTs), there is a lack of structural data for this versatile class of enzymes. Here, the cloning, expression, purification and crystallization of an essential 329-amino-acid (34.8 kDa) putative GT of the classic GT-A fold implicatedmore » in mycobacterial cell-wall biosynthesis are reported. Crystals of MAP2569c from Mycobacterium avium subsp. paratuberculosis were grown in 1.6 M monoammonium dihydrogen phosphate and 0.1 M sodium citrate pH 5.5. A complete data set was collected to 1.8 Å resolution using synchrotron radiation from a crystal belonging to space group P4{sub 1}2{sub 1}2.« less

  19. Establishment of an in vitro cell line experimental system for the study of inhalational anesthetic mechanisms.

    PubMed

    Nagamoto, Seiji; Iijima, Norio; Ishii, Hirotaka; Takumi, Ken; Higo, Shimpei; Aikawa, Satoko; Anzai, Megumi; Matsuo, Izumi; Nakagawa, Shinji; Takashima, Naoyuki; Shigeyoshi, Yasufumi; Sakamoto, Atsuhiro; Ozawa, Hitoshi

    2016-05-04

    General anesthesia affects the expression of clock genes in various organs. Expression of Per2, a core component of the circadian clock, is markedly and reversibly suppressed by sevoflurane in the suprachiasmatic nucleus (SCN), and is considered to be a biochemical marker of anesthetic effect in the brain. The SCN contains various types of neurons, and this complexity makes it difficult to investigate the molecular mechanisms of anesthesia. Here, we established an in vitro experimental system using a cell line to investigate the mechanisms underlying anesthetic action. Development of the system comprised two steps: first, we developed a system for application of inhalational anesthetics and incubation; next, we established cultures of anesthetic-responsive cells expressing mPer2 promoter-dLuc. GT1-7 cells, derived from the mouse hypothalamus, responded to sevoflurane by reversibly decreasing mPer2-promoter-driven bioluminescence. Interestingly, the suppression of bioluminescence was found only in the serum-starved GT1-7 cells, which showed neuron-like morphology, but not in growing cells, suggesting that neuron-like characteristics are required for anesthetic effects in GT1-7 cells. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. The alpha-7 nicotinic acetylcholine receptor is involved in a direct inhibitory effect of nicotine on GnRH release: In vitro studies.

    PubMed

    Messi, Elio; Pimpinelli, Federica; Andrè, Valentina; Rigobello, Chiara; Gotti, Cecilia; Maggi, Roberto

    2018-01-15

    The activation of nicotinic cholinergic receptors (nAChR) inhibits the reproductive axis; however, it is not clear whether nicotine may directly modulate the release of hypothalamic gonadotropin-releasing hormone (GnRH). Experiments carried out in GT1-1 immortalized GnRH neurons reveal the presence of a single class of high affinity α4β2 and α7 nAchR subtypes. The exposure of GT1-1 cells to nicotine does not modify the basal accumulation of GnRH. However, nicotine was found to modify GnRH pulsatility in perifusion experiments and inhibits, the release of GnRH induced by prostaglandin E 1 or by K + -induced cell depolarization; these effects were reversed by D-tubocurarine and α-bungarotoxin. In conclusion, the results reported here indicate that: functional nAChRs are present on GT1-1 cells, the activation of the α-bungarotoxin-sensitive subclass (α7) produces an inhibitory effect on the release of GnRH and that the direct action of nicotine on GnRH neurons may be involved in reducing fertility of smokers. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Endogenous IL-33 is highly expressed in mouse epithelial barrier tissues, lymphoid organs, brain, embryos, and inflamed tissues: in situ analysis using a novel Il-33-LacZ gene trap reporter strain.

    PubMed

    Pichery, Mélanie; Mirey, Emilie; Mercier, Pascale; Lefrancais, Emma; Dujardin, Arnaud; Ortega, Nathalie; Girard, Jean-Philippe

    2012-04-01

    IL-33 (previously known as NF from high endothelial venules) is an IL-1 family cytokine that signals through the ST2 receptor and drives cytokine production in mast cells, basophils, eosinophils, invariant NKT and NK cells, Th2 lymphocytes, and type 2 innate immune cells (natural helper cells, nuocytes, and innate helper 2 cells). Little is known about endogenous IL-33; for instance, the cellular sources of IL-33 in mouse tissues have not yet been defined. In this study, we generated an Il-33-LacZ gene trap reporter strain (Il-33(Gt/Gt)) and used this novel tool to analyze expression of endogenous IL-33 in vivo. We found that the Il-33 promoter exhibits constitutive activity in mouse lymphoid organs, epithelial barrier tissues, brain, and embryos. Immunostaining with anti-IL-33 Abs, using Il-33(Gt/Gt) (Il-33-deficient) mice as control, revealed that endogenous IL-33 protein is highly expressed in mouse epithelial barrier tissues, including stratified squamous epithelia from vagina and skin, as well as cuboidal epithelium from lung, stomach, and salivary gland. Constitutive expression of IL-33 was not detected in blood vessels, revealing the existence of species-specific differences between humans and mice. Importantly, IL-33 protein was always localized in the nucleus of producing cells with no evidence for cytoplasmic localization. Finally, strong expression of the Il-33-LacZ reporter was also observed in inflamed tissues, in the liver during LPS-induced endotoxin shock, and in the lung alveoli during papain-induced allergic airway inflammation. Together, our findings support the possibility that IL-33 may function as a nuclear alarmin to alert the innate immune system after injury or infection in epithelial barrier tissues.

  2. Effect of common polymorphisms of the farnesoid X receptor and bile acid transporters on the pharmacokinetics of ursodeoxycholic acid.

    PubMed

    Hu, Miao; Fok, Benny S P; Wo, Siu-Kwan; Lee, Vincent H L; Zuo, Zhong; Tomlinson, Brian

    2016-01-01

    Ursodeoxycholic acid (UDCA), a natural, dihydroxy bile acid, promotes gallstone dissolution and has been attributed with several other beneficial effects. The farnesoid X receptor (FXR) may influence the pharmacokinetics of UDCA by modulating the expression of bile acid transporters. This exploratory study examined whether common functional polymorphisms in FXR and in bile acid transporter genes affect the pharmacokinetics of exogenous UDCA. Polymorphisms in genes for transporters involved in bile acid transport, solute carrier organic anion 1B1 (SLCO1B1) 388A>G and 521T>C, solute carrier 10A1 (SLC10A1) 800 C>T and ATP-binding cassette B11 (ABCB11) 1331T>C, and the FXR -1G>T polymorphism were genotyped in 26 male Chinese subjects who ingested single oral 500-mg doses of UDCA. Plasma concentrations of UDCA and its major conjugate metabolite glycoursodeoxycholic acid (GUDCA) were determined. The mean systemic exposure of UDCA was higher in the five subjects with one copy of the FXR -1G>T variant allele than in those homozygous for the wild-type allele (n = 21) (AUC0-24 h : 38.5 ± 28.2 vs. 20.9 ± 8.0 μg h/mL, P = 0.021), but this difference appeared mainly due to one outlier with the -1GT genotype and elevated baseline and post-treatment UDCA concentrations. After excluding the outlier, body weight was the only factor associated with plasma concentrations of UDCA and there were no significant associations with the other polymorphisms examined. None of the polymorphisms affected the pharmacokinetics of GUDCA. This study showed that the common polymorphisms in bile acid transporters had no significant effect on the pharmacokinetics of exogenous UDCA but an effect of the FXR polymorphism cannot be excluded. © 2015 Wiley Publishing Asia Pty Ltd.

  3. Total enantioselectivity in the DNA binding of the dinuclear ruthenium(II) complex [[Ru(Me2bpy)2]2(mu-bpm)]4+ [bpm = 2,2'-bipyrimidine; Me2bpy = 4,4'-dimethyl-2,2'-bipyridine].

    PubMed

    Smith, Jayden A; Collins, J Grant; Patterson, Bradley T; Keene, F Richard

    2004-05-07

    The binding of the three stereoisomers (DeltaDelta-, LambdaLambda- and DeltaLambda-) of the dinuclear ruthenium(II) complex [[Ru(Me2bpy)2]2(mu-bpm)]4+ [Me2bpy = 4,4'-dimethyl-2,2'-bipyridine; bpm = 2,2'-bipyrimidine] to a tridecanucleotide containing a single adenine bulge has been studied by 1H NMR spectroscopy. The addition of the DeltaDelta-isomer to d(CCGAGAATTCCGG)2 induced significant chemical shift changes for the base and sugar resonances of the residues at the bulge site (G3A4G5/C11C10), whereas small shifts were observed upon addition of the enantiomeric LambdaLambda-form. NOESY spectra of the tridecanucleotide bound with the DeltaDelta-isomer revealed intermolecular NOE's between the metal complex and the nucleotide residues at the bulge site, while only weak NOE's were observed to terminal residues to the LambdaLambda-form. Competitive binding studies were performed where both enantiomers were simultaneously added to the tridecanucleotide, and for all ratios of the two stereoisomers the DeltaDelta-isomer remained selectively bound at the bulge site with the LambdaLambda-enantiomer localised at the terminal regions of the tridecanucleotide. The meso-diastereoisomer (DeltaLambda) was found to bind to the tridecanucleotide with characteristics intermediate between the DeltaDelta- and LambdaLambda-enantiomers of the rac form. Two distinct sets of metal complex resonances were observed, with one set having essentially the same shift as the free metal complex, whilst the other set of resonances exhibited significant shifts. The NOE data indicated that the meso-diastereoisomer does not bind as selectively as the DeltaDelta-isomer, with NOE's observed to a greater number of nucleotide residues compared to the DeltaDelta-form. This study provides a rare example of total enantioselectivity in the binding of an inert transition metal complex to DNA, produced by the shape recognition of both ruthenium(II) centres.

  4. High resolution spectroscopic study of Be Λ 10

    DOE PAGES

    Gogami, T.; Chen, C.; Kawama, D.; ...

    2016-03-10

    Spectroscopy of amore » $$^{10}_{\\Lambda}$$Be hypernucleus was carried out at JLab Hall C using the $$(e,e^{\\prime}K^{+})$$ reaction. A new magnetic spectrometer system (SPL+HES+HKS), specifically designed for high resolution hypernuclear spectroscopy, was used to obtain an energy spectrum with a resolution of 0.78 MeV (FWHM). The well-calibrated spectrometer system of the present experiment using the $$p(e,e^{\\prime}K^{+})\\Lambda,\\Sigma^{0}$$ reactions allowed us to determine the energy levels, and the binding energy of the ground state peak (mixture of 1$$^{-}$$ and 2$$^{-}$$ states) was obtained to be B$$_{\\Lambda}$$=8.55$$\\pm$$0.07(stat.)$$\\pm$$0.11(sys.) MeV. Furthermore, the result indicates that the ground state energy is shallower than that of an emulsion study by about 0.5 MeV which provides valuable experimental information on charge symmetry breaking effect in the $$\\Lambda N$$ interaction.« less

  5. Observation of Exclusive B Decays to Final States Containing a Charmed Baryon

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

    Jessop, Colin P.

    2003-05-23

    Using data collected in the region of the {Upsilon}(4S) resonance with the CLEO-II detector, they report on the first observation of exclusive decays of the B meson to final states with a charmed baryon. They have measured the branching fractions {Beta}(B{sup -} {yields} {Lambda}{sub c}{sup +}{bar p}{pi}{sup -}) = (0.62{sub -0.20}{sup +0.23} {+-} 0.11 {+-} 0.10) x 10{sup -3} and {Beta}({bar B}{sup 0} {yields} {Lambda}{sub c}{sup +}{bar p}{pi}{sup +}{pi}{sup -}) = (1.33{sub -0.42}{sup +0.46} {+-} 0.31 {+-} 0.21) x 10{sup -3}. In addition, they report upper limits for final states of the form {bar B} {yields} {Lambda}{sub c}{sup +}{bar p}(n{pi})more » and {Lambda}{sub c}{sup +}{bar p}(n{pi}){pi}{sup 0} where (n{pi}) denotes up to four charged pions.« less

  6. Mechanistic Characterization of GS-9190 (Tegobuvir), a Novel Nonnucleoside Inhibitor of Hepatitis C Virus NS5B Polymerase▿

    PubMed Central

    Shih, I-hung; Vliegen, Inge; Peng, Betty; Yang, Huiling; Hebner, Christy; Paeshuyse, Jan; Pürstinger, Gerhard; Fenaux, Martijn; Tian, Yang; Mabery, Eric; Qi, Xiaoping; Bahador, Gina; Paulson, Matthew; Lehman, Laura S.; Bondy, Steven; Tse, Winston; Reiser, Hans; Lee, William A.; Schmitz, Uli; Neyts, Johan; Zhong, Weidong

    2011-01-01

    GS-9190 (Tegobuvir) is a novel imidazopyridine inhibitor of hepatitis C virus (HCV) RNA replication in vitro and has demonstrated potent antiviral activity in patients chronically infected with genotype 1 (GT1) HCV. GS-9190 exhibits reduced activity against GT2a (JFH1) subgenomic replicons and GT2a (J6/JFH1) infectious virus, suggesting that the compound's mechanism of action involves a genotype-specific viral component. To further investigate the GS-9190 mechanism of action, we utilized the susceptibility differences between GT1b and GT2a by constructing a series of replicon chimeras where combinations of 1b and 2a nonstructural proteins were encoded within the same replicon. The antiviral activities of GS-9190 against the chimeric replicons were reduced to levels comparable to that of the wild-type GT2a replicon in chimeras expressing GT2a NS5B. GT1b replicons in which the β-hairpin region (amino acids 435 to 455) was replaced by the corresponding sequence of GT2a were markedly less susceptible to GS-9190, indicating the importance of the thumb subdomain of the polymerase in this effect. Resistance selection in GT1b replicon cells identified several mutations in NS5B (C316Y, Y448H, Y452H, and C445F) that contributed to the drug resistance phenotype. Reintroduction of these mutations into wild-type replicons conferred resistance to GS-9190, with the number of NS5B mutations correlating with the degree of resistance. Analysis of GS-9190 cross-resistance against previously reported NS5B drug-selected mutations showed that the resistance pattern of GS-9190 is different from other nonnucleoside inhibitors. Collectively, these data demonstrate that GS-9190 represents a novel class of nonnucleoside polymerase inhibitors that interact with NS5B likely through involvement of the β-hairpin in the thumb subdomain. PMID:21746939

  7. In vivo gene delivery and expression by bacteriophage lambda vectors.

    PubMed

    Lankes, H A; Zanghi, C N; Santos, K; Capella, C; Duke, C M P; Dewhurst, S

    2007-05-01

    Bacteriophage vectors have potential as gene transfer and vaccine delivery vectors because of their low cost, safety and physical stability. However, little is known concerning phage-mediated gene transfer in mammalian hosts. We therefore performed experiments to examine phage-mediated gene transfer in vivo. Mice were inoculated with recombinant lambda phage containing a mammalian expression cassette encoding firefly luciferase (luc). Efficient, dose-dependent in vivo luc expression was detected, which peaked within 24 h of delivery and declined to undetectable levels within a week. Display of an integrin-binding peptide increased cellular internalization of phage in vitro and enhanced phage-mediated gene transfer in vivo. Finally, in vivo depletion of phagocytic cells using clodronate liposomes had only a minor effect on the efficiency of phage-mediated gene transfer. Unmodified lambda phage particles are capable of transducing mammalian cells in vivo, and may be taken up -- at least in part -- by nonphagocytic mechanisms. Surface modifications that enhance phage uptake result in more efficient in vivo gene transfer. These experiments shed light on the mechanisms involved in phage-mediated gene transfer in vivo, and suggest new approaches that may enhance the efficiency of this process.

  8. Chloride conducting light activated channel GtACR2 can produce both cessation of firing and generation of action potentials in cortical neurons in response to light.

    PubMed

    Malyshev, A Y; Roshchin, M V; Smirnova, G R; Dolgikh, D A; Balaban, P M; Ostrovsky, M A

    2017-02-15

    Optogenetics is a powerful technique in neuroscience that provided a great success in studying the brain functions during the last decade. Progress of optogenetics crucially depends on development of new molecular tools. Light-activated cation-conducting channelrhodopsin2 was widely used for excitation of cells since the emergence of optogenetics. In 2015 a family of natural light activated chloride channels GtACR was identified which appeared to be a very promising tool for using in optogenetics experiments as a cell silencer. Here we examined properties of GtACR2 channel expressed in the rat layer 2/3 pyramidal neurons by means of in utero electroporation. We have found that despite strong inhibition the light stimulation of GtACR2-positive neurons can surprisingly lead to generation of action potentials, presumably initiated in the axonal terminals. Thus, when using the GtACR2 in optogenetics experiments, its ability to induce action potentials should be taken into account. Our results also open an interesting possibility of using the GtACR2 both as cell silencer and cell activator in the same experiment varying the pattern of light stimulation. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Chronic hepatitis C infection and liver disease in HIV co-infected patients in Asia

    PubMed Central

    Durier, Nicolas; Yunihastuti, Evy; Ruxrungtham, Kiat; Van Kinh, Nguyen; Kamarulzaman, Adeeba; Boettiger, David; Widhani, Alvina; Avihingsanon, Anchalee; Huy, Bui Vu; Omar, Sharifah Faridah binti Syed; Sanityoso, Andri; Chittmittrapap, Salyavit; Dung, Nguyen Thi Hoai; Pillai, Veena; Suwan-Ampai, Tuangporn; Law, Matthew; Sohn, Annette H.; Matthews, Gail

    2016-01-01

    Data on markers of hepatitis C virus (HCV) disease in HIV-HCV co-infected patients in resource-limited settings are scarce. We assessed HCV-RNA, HCV genotype (GT), IL28B GT, and liver fibrosis (FibroScan®) in 480 HIV-infected patients with positive HCV antibody in four HIV treatment centers in South East Asia. We enrolled 165 (34.4%) patients in Jakarta, 158 (32.9%) in Bangkok, 110 (22.9%) in Hanoi, and 47 (9.8%) in Kuala Lumpur. Overall, 426 (88.8%) were male, the median (IQR) age was 38.1 (34.7–42.5) years, 365 (76.0%) reported HCV exposure through injecting drug use, and 453 (94.4%) were on combination antiretroviral therapy. The median (IQR) CD4 count was 446 (325–614) cells/mm3 and 208 (94.1%) of 221 patients tested had HIV-1 RNA <400 copies/ml. A total of 412 (85.8%) had detectable HCV-RNA, at a median (IQR) of 6.2 (5.4-6.6) log10 IU/mL. Among 380 patients with HCV GT, 223 (58.7%) had GT1, 97 (25.5%) had GT3, 43 (11.3%) had GT6, 8 (2.1%) had GT4, 2 (0.5%) had GT2, and 7 (1.8%) had indeterminate GT. Of 222 patients with IL28B testing, 189 (85.1%) had rs12979860 CC genotype, and 199 (89.6%) had rs8099917 TT genotype. Of 380 patients with FibroScan®, 143 (37.6%) had no/mild liver fibrosis (F0-F1), 83 (21.8%) had moderate fibrosis (F2), 74 (19.5%) had severe fibrosis (F3), and 79 (20.8%) had cirrhosis (F4). One patient (0.3%) had FibroScan® failure. A high proportion of HIV-HCV co-infected patients had chronic HCV infection. HCV GT1 was predominant, and 62% of patients had liver disease warranting prompt treatment (>=F2). PMID:27917597

  10. Chronic hepatitis C infection and liver disease in HIV-coinfected patients in Asia.

    PubMed

    Durier, N; Yunihastuti, E; Ruxrungtham, K; Kinh, N V; Kamarulzaman, A; Boettiger, D; Widhani, A; Avihingsanon, A; Huy, B V; Syed Omar, S F B; Sanityoso, A; Chittmittrapap, S; Dung, N T H; Pillai, V; Suwan-Ampai, T; Law, M; Sohn, A H; Matthews, G

    2017-03-01

    Data on markers of hepatitis C virus (HCV) disease in HIV-HCV-coinfected patients in resource-limited settings are scarce. We assessed HCV RNA, HCV genotype (GT), IL28B GT and liver fibrosis (FibroScan ® ) in 480 HIV-infected patients with positive HCV antibody in four HIV treatment centres in South-East Asia. We enrolled 165 (34.4%) patients in Jakarta, 158 (32.9%) in Bangkok, 110 (22.9%) in Hanoi and 47 (9.8%) in Kuala Lumpur. Overall, 426 (88.8%) were male, the median (IQR) age was 38.1 (34.7-42.5) years, 365 (76.0%) reported HCV exposure through injecting drug use, and 453 (94.4%) were on combination antiretroviral therapy. The median (IQR) CD4 count was 446 (325-614) cells/mm 3 and 208 (94.1%) of 221 patients tested had HIV-1 RNA <400 copies/mL. A total of 412 (85.8%) had detectable HCV RNA, at a median (IQR) of 6.2 (5.4-6.6) log 10 IU/mL. Among 380 patients with HCV GT, 223 (58.7%) had GT1, 97 (25.5%) had GT3, 43 (11.3%) had GT6, eight (2.1%) had GT4, two (0.5%) had GT2, and seven (1.8%) had indeterminate GT. Of 222 patients with IL28B testing, 189 (85.1%) had rs12979860 CC genotype, and 199 (89.6%) had rs8099917 TT genotype. Of 380 patients with FibroScan ® , 143 (37.6%) had no/mild liver fibrosis (F0-F1), 83 (21.8%) had moderate fibrosis (F2), 74 (19.5%) had severe fibrosis (F3), and 79 (20.8%) had cirrhosis (F4). One patient (0.3%) had FibroScan ® failure. In conclusion, a high proportion of HIV-HCV-coinfected patients had chronic HCV infection. HCV GT1 was predominant, and 62% of patients had liver disease warranting prompt treatment (≥F2). © 2016 John Wiley & Sons Ltd.

  11. Sub-optimal pH Preadaptation Improves the Survival of Lactobacillus plantarum Strains and the Malic Acid Consumption in Wine-Like Medium

    PubMed Central

    Succi, Mariantonietta; Pannella, Gianfranco; Tremonte, Patrizio; Tipaldi, Luca; Coppola, Raffaele; Iorizzo, Massimo; Lombardi, Silvia Jane; Sorrentino, Elena

    2017-01-01

    Forty-two oenological strains of Lb. plantarum were assessed for their response to ethanol and pH values generally encountered in wines. Strains showed a higher variability in the survival when exposed to low pH (3.5 or 3.0) than when exposed to ethanol (10 or 14%). The study allowed to individuate the highest ethanol concentration (8%) and the lowest pH value (4.0) for the growth of strains, even if the maximum specific growth rate (μmax) resulted significantly reduced by these conditions. Two strains (GT1 and LT11) preadapted to 2% ethanol and cultured up to 14% of ethanol showed a higher growth than those non-preadapted when they were cultivated at 8% of ethanol. The evaluation of the same strains preadapted to low pH values (5.0 and 4.0) and then grown at pH 3.5 or 3.0 showed only for GT1 a sensitive μmax increment when it was cultivated in MRS at pH 3 after a preadaptation to pH 5.0. The survival of GT1 and LT11 was evaluated in Ringer's solution at 14% ethanol after a long-term adaptation in MRS with 2% ethanol or in MRS with 2% ethanol acidified at pH 5.0 (both conditions, BC). Analogously, the survival was evaluated at pH 3.5 after a long-term adaptation in MRS at pH 5.0 or in MRS BC. The impact of the physiologic state (exponential phase vs stationary phase) on the survival was also evaluated. Preadapted cells showed the same behavior of non-preadapted cells only when cultures were recovered in the stationary phase. Mathematical functions were individuated for the description of the survival of GT1 and LT11 in MRS at 14% ethanol or at pH 3.5. Finally, a synthetic wine (SW) was used to assess the behavior of Lb. plantarum GT1 and LT11 preadapted in MRS at 2% ethanol or at pH 5.0 or in BC. Only GT1 preadapted to pH 5.0 and collected in the stationary phase showed constant values of microbial counts after incubation for 15 days at 20°C. In addition, after 15 days the L-malic acid resulted completely degraded and the pH value increased of about 0.3 units. PMID:28382030

  12. Attitudes of Patients With Cancer About Personalized Medicine and Somatic Genetic Testing

    PubMed Central

    Gray, Stacy W.; Hicks-Courant, Katherine; Lathan, Christopher S.; Garraway, Levi; Park, Elyse R.; Weeks, Jane C.

    2012-01-01

    Purpose: Dramatic advances in genomic technology stand to revolutionize cancer care; however, little is known about patients' understanding and acceptance of personalized medicine and widespread genetic testing (GT). Patients and Methods: We conducted a formative, semi-structured interview study with a random sample of patients with lung, colorectal, and breast cancers to assess awareness of personalized medicine and GT and attitudes about somatic GT. Willingness to undergo GT was elicited through hypothetic scenarios. Results: Sixty-nine patients participated; 71% were women; 42% were black; median age was 59 years; and 42% had an education level ≥ college. We found that a majority of patients either were not aware of the term “personalized medicine” or defined it in unexpected ways. Although many patients identified relevant benefits of somatic testing (eg, informs treatment), many patients also expressed significant concerns (ie, psychological harm and discrimination). A majority of patients expressed a willingness to undergo somatic (predictive, 96%, prognostic, 93%) and germline (cancer risk without incidental information, 87%; cancer risk with incidental information, 81%; pharmacogenetic, 91%) testing; however, far fewer patients expressed a willingness to undergo full genome sequencing (62%). Reluctance was attributed to concerns over incidental findings, information overload, and the lack of a clear benefit. Conclusion: Many patients relayed misunderstandings about somatic testing and a reluctance to undergo full sequencing; oncologists must carefully consider how they present testing to patients so that concerns over discrimination and psychological harm do not hinder test uptake. More work is needed to identify effective ways to communicate complex genomic concepts to patients and research participants. PMID:23598841

  13. Mature middle and inner ears express Chd7 and exhibit distinctive pathologies in a mouse model of CHARGE syndrome.

    PubMed

    Hurd, Elizabeth A; Adams, Meredith E; Layman, Wanda S; Swiderski, Donald L; Beyer, Lisa A; Halsey, Karin E; Benson, Jennifer M; Gong, Tzy-Wen; Dolan, David F; Raphael, Yehoash; Martin, Donna M

    2011-12-01

    Heterozygous mutations in the gene encoding chromodomain-DNA-binding-protein 7 (CHD7) cause CHARGE syndrome, a multiple anomaly condition which includes vestibular dysfunction and hearing loss. Mice with heterozygous Chd7 mutations exhibit semicircular canal dysgenesis and abnormal inner ear neurogenesis, and are an excellent model of CHARGE syndrome. Here we characterized Chd7 expression in mature middle and inner ears, analyzed morphological features of mutant ears and tested whether Chd7 mutant mice have altered responses to noise exposure and correlated those responses to inner and middle ear structure. We found that Chd7 is highly expressed in mature inner and outer hair cells, spiral ganglion neurons, vestibular sensory epithelia and middle ear ossicles. There were no obvious defects in individual hair cell morphology by prestin immunostaining or scanning electron microscopy, and cochlear innervation appeared normal in Chd7(Gt)(/+) mice. Hearing thresholds by auditory brainstem response (ABR) testing were elevated at 4 and 16 kHz in Chd7(Gt)(/+) mice, and there were reduced distortion product otoacoustic emissions (DPOAE). Exposure of Chd7(Gt)(/+) mice to broadband noise resulted in variable degrees of hair cell loss which inversely correlated with severity of stapedial defects. The degrees of hair cell loss and threshold shifts after noise exposure were more severe in wild type mice than in mutants. Together, these data indicate that Chd7(Gt)(/+) mice have combined conductive and sensorineural hearing loss, correlating with changes in both middle and inner ears. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Mature middle and inner ears express Chd7 and exhibit distinctive pathologies in a mouse model of CHARGE syndrome

    PubMed Central

    Hurd, Elizabeth A.; Adams, Meredith E.; Layman, Wanda S.; Swiderski, Donald L.; Beyer, Lisa A.; Halsey, Karin E.; Benson, Jennifer M.; Gong, Tzy-Wen; Dolan, David F.; Raphael, Yehoash; Martin, Donna M.

    2011-01-01

    Heterozygous mutations in the gene encoding chromodomain-DNA-binding-protein 7 (CHD7) cause CHARGE syndrome, a multiple anomaly condition which includes vestibular dysfunction and hearing loss. Mice with heterozygous Chd7 mutations exhibit semicircular canal dysgenesis and abnormal inner ear neurogenesis, and are an excellent model of CHARGE syndrome. Here we characterized Chd7 expression in mature middle and inner ears, analyzed morphological features of mutant ears and tested whether Chd7 mutant mice have altered responses to noise exposure and correlated those responses to inner and middle ear structure. We found that Chd7 is highly expressed in mature inner and outer hair cells, spiral ganglion neurons, vestibular sensory epithelia and middle ear ossicles. There were no obvious defects in individual hair cell morphology by Prestin immunostaining or scanning electron microscopy, and cochlear innervation appeared normal in Chd7Gt/+ mice. Hearing thresholds by auditory brainstem response (ABR) testing were elevated at 4 and 16 kHz in Chd7Gt/+ mice, and there were reduced distortion product otoacoustic emissions (DPOAE). Exposure of Chd7Gt/+ mice to broadband noise resulted in variable degrees of hair cell loss which inversely correlated with severity of stapedial defects. The degrees of hair cell loss and threshold shifts after noise exposure were more severe in wild type mice than in mutants. Together, these data indicate that Chd7Gt/+ mice have combined conductive and sensorineural hearing loss, correlating with changes in both middle and inner ears. PMID:21875659

  15. The effect of maternal diabetes on the Wnt-PCP pathway during embryogenesis as reflected in the developing mouse eye

    PubMed Central

    López-Escobar, Beatriz; Cano, David A.; Rojas, Anabel; de Felipe, Beatriz; Palma, Francisco; Sánchez-Alcázar, José A.; Henderson, Deborah; Ybot-González, Patricia

    2015-01-01

    Embryopathies that develop as a consequence of maternal diabetes have been studied intensely in both experimental and clinical scenarios. Accordingly, hyperglycaemia has been shown to downregulate the expression of elements in the non-canonical Wnt-PCP pathway, such as the Dishevelled-associated activator of morphogenesis 1 (Daam1) and Vangl2. Daam1 is a formin that is essential for actin polymerization and for cytoskeletal reorganization, and it is expressed strongly in certain organs during mouse development, including the eye, neural tube and heart. Daam1gt/gt and Daam1gt/+ embryos develop ocular defects (anophthalmia or microphthalmia) that are similar to those detected as a result of hyperglycaemia. Indeed, studying the effects of maternal diabetes on the Wnt-PCP pathway demonstrated that there was strong association with the Daam1 genotype, whereby the embryopathy observed in Daam1gt/+ mutant embryos of diabetic dams was more severe. There was evidence that embryonic exposure to glucose in vitro diminishes the expression of genes in the Wnt-PCP pathway, leading to altered cytoskeletal organization, cell shape and cell polarity in the optic vesicle. Hence, the Wnt-PCP pathway appears to influence cell morphology and cell polarity, events that drive the cellular movements required for optic vesicle formation and that, in turn, are required to maintain the fate determination. Here, we demonstrate that the Wnt-PCP pathway is involved in the early stages of mouse eye development and that it is altered by diabetes, provoking the ocular phenotype observed in the affected embryos. PMID:25540130

  16. Reconstructing decades of glacial mass loss in the Canadian Arctic Archipelago

    NASA Astrophysics Data System (ADS)

    Noël, Brice; van de Berg, Willem Jan; Lhermitte, Stef; Wouters, Bert; van den Broeke, Michiel

    2017-04-01

    The Canadian Arctic Archipelago (CAA) comprises multiple small glaciers and ice caps mostly concentrated on Ellesmere and Baffin Islands situated in the north (NCAA) and south (SCAA) of the archipelago, respectively. Because they cover a relatively small area and show complex geometries, current regional climate models, generally running at 5 to 20 km horizontal resolution, struggle to accurately resolve surface mass change patterns. Here, we present a 58-year (1958-2015) reconstruction of daily, 1 km surface mass balance (SMB) of the CAA, statistically downscaled from the output of the regional climate model RACMO2.3 at 11 km. By correcting for biases in elevation and ice albedo, the downscaling method significantly improves mass loss estimates over narrow outlet glaciers and isolated ice fields through better resolved marginal meltwater runoff. During the last two decades, CAA glaciers have experienced warmer conditions (+1.1°C) resulting in continued mass loss. NCAA and SCAA mass loss accounted for -24.7 ± 18.0 Gt yr-1 and -21.9 ± 8.2 Gt yr-1 respectively, almost tripling (-8.4 Gt yr-1) and doubling (-11.8 Gt yr-1) the 1958-1995 average. Following the recent warming, enhanced meltwater production reduced the refreezing capacity of inland firn layers by about 6%. While the interior of NCAA ice caps can still buffer most of the additional melt, the lack of a perennial firn area over low-lying SCAA glaciers caused uninterrupted mass loss since the 1980s, which, in the absence of significant refreezing capacity, indicates inevitable disappearance of these highly sensitive glaciers.

  17. Imaging The Genetic Code of a Virus

    NASA Astrophysics Data System (ADS)

    Graham, Jenna; Link, Justin

    2013-03-01

    Atomic Force Microscopy (AFM) has allowed scientists to explore physical characteristics of nano-scale materials. However, the challenges that come with such an investigation are rarely expressed. In this research project a method was developed to image the well-studied DNA of the virus lambda phage. Through testing and integrating several sample preparations described in literature, a quality image of lambda phage DNA can be obtained. In our experiment, we developed a technique using the Veeco Autoprobe CP AFM and mica substrate with an appropriate absorption buffer of HEPES and NiCl2. This presentation will focus on the development of a procedure to image lambda phage DNA at Xavier University. The John A. Hauck Foundation and Xavier University

  18. Polyphenol-rich beverages enhance zinc uptake and metallothionein expression in Caco-2 cells.

    PubMed

    Sreenivasulu, Kilari; Raghu, Pullakhandam; Nair, K Madhavan

    2010-05-01

    The effect of red wine (RW), red grape juice (RGJ), green tea (GT), and representative polyphenols on Caco-2 cell (65)Zn uptake was explored. RW, RGJ, and GT enhanced the uptake of zinc from rice matrix. Fractionation of RW revealed that enhancing activity of zinc uptake was exclusively resided in the polyphenol fraction. Among the polyphenols tested, only tannic acid and quercitin stimulated the uptake of zinc while others did not influence the uptake. In tune with these results, only tannic acid and quercitin competed with zinquin (a zinc selective fluorophore) for zinc in vitro. Although all the polyphenols tested appear to enhance the expression of metallothionein (MT), the induction was higher with tannic acid, quercitin, and RW extract. Furthermore, phytic acid abrogated the tannic acid-induced MT expression. These results suggest that polyphenol-rich beverages, tannic acid, and quercitin bind and stimulate the zinc uptake and MT expression in Caco-2 cells.

  19. A computable expression of closure to efficient causation.

    PubMed

    Mossio, Matteo; Longo, Giuseppe; Stewart, John

    2009-04-07

    In this paper, we propose a mathematical expression of closure to efficient causation in terms of lambda-calculus; we argue that this opens up the perspective of developing principled computer simulations of systems closed to efficient causation in an appropriate programming language. An important implication of our formulation is that, by exhibiting an expression in lambda-calculus, which is a paradigmatic formalism for computability and programming, we show that there are no conceptual or principled problems in realizing a computer simulation or model of closure to efficient causation. We conclude with a brief discussion of the question whether closure to efficient causation captures all relevant properties of living systems. We suggest that it might not be the case, and that more complex definitions could indeed create crucial some obstacles to computability.

  20. High-resolution oscillator strength measurements for the A(v') - X(0) bands of carbon monoxide with 11 less than or equal to v' less than or equal to 14

    NASA Technical Reports Server (NTRS)

    Smith, Peter L.; Stark, G.; Yoshino, K.; Ito, K.

    1994-01-01

    Band oscillator strengths (f-values) for four bands of the Fourth Positive system (A (1)Pi - Chi(sup 1) Sigma(+)) of CO have been determined from high-resolution (lambda/Delta lambda approximately equal to 150,000) absorption spectra. The bands, (14, 0) through (11, 0), are at wavelengths between 121 and 127 nm. Our f-values for the (11, 0) and (12, 0) bands support those of Chan, Cooper, & Brion (1993), which have been shown to be consistent with observations of CO in the clouds in the line of sight to zeta Oph. Our f-values for the (13, 0) and (14, 0) bands are the first directly measured values for these bands.

  1. Molecular cloning of the human UMP synthase gene and characterization of point mutations in two hereditary orotic aciduria families

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

    Suchi, Mariko; Mizuno, Haruo; Tsuboi, Takashi

    Uridine monophosphate (UMP) synthase is a bifunctional enzyme catalyzing the last two steps of de novo pyrimidine biosynthesis, orotate phosphoribosyltransferase (OPRT) and orotidine-5{prime}-monophosphate decarboxylase (ODC). Loss of either enzymatic activity results in hereditary orotic aciduria, a rare autosomal recessive disorder characterized by retarded growth, anemia, and excessive urinary excretion of orotic acid. We have isolated the UMP synthase chromosomal gene from a {lambda}EMBL-3 human genomic library and report a single-copy gene spanning {approximately}15 kb. The UMP synthase genomic structure encodes six exons ranging in size from 115 bp to 672 bp, and all splicing junctions adhere to the canonical GT/AGmore » rule. Cognate promoter elements implicated in glucocorticoid- and cAMP-mediated regulation as well as in liver-, myeloid-, and lymphocyte-specific expression are located within the 5{prime} flanking sequence. Molecular investigation of UMP synthase deficiency in a Japanese orotic aciduria patient revealed mutations R96G (A- to-G transition; nt 286) and G429R (G-to-C transversion; nt 1285) in one allele and V109G (T-to-G transversion; nt 326) in the other allele. Expression of human UMP synthase cDNAs containing these mutations in pyrimidine auxotrophic Escherichia coli and in recombinant baculovirus-infected Sf21 cells demonstrates impaired activity presumably associated with the urinary orotic acid substrate accumulations observed in vivo. We further establish the identity of two polymorphisms, G213A ({nu} = .26) and 440 Gpoly ({nu} = .27) located in exons 3 and 6, respectively, which did not significantly compromise either OPRT or ODC function. 76 refs., 5 figs., 7 tabs.« less

  2. Distributed modeling of diffusive solute transport in peritoneal dialysis.

    PubMed

    Waniewski, Jacek

    2002-01-01

    The diffusive transport between blood and an ex-tissue medium (dialysis fluid) is evaluated using a mathematical model that takes into account the (quasicontinuous) distribution of capillaries within the tissue at various distances from the tissue surface, and includes diffusive-convective transport through the capillary wall and lymphatic absorption from the tissue. General formulas for solute penetration depth, lambda, and for the diffusive mass transport coefficient for the transport between blood and dialysis fluid, K(BD), are provided in terms of local transport coefficients for capillary wall, tissue, and lymphatic absorption. For pure diffusive transport between blood and dialysis fluid and thick tissue layers (i.e., if the solute penetration depth is much lower than the tissue thickness) these formulas yield previously known expressions. It is shown that apparent tissue layers, with widths lambdaTBL and lambdaT, respectively, may be defined according to the values of local transport parameters in such a way that K(BD) is equal to the solute clearance K(TBL) from the tissue by blood and lymph for a layer with width lambdaTBL or to the solute clearance K(T) from blood to dialysate by diffusion through the tissue layer with width lambdaT. For tissue layers with width much higher than the penetration depth: lambdaT approximately = lambdaTBL approximately = lambda. These characteristic width lengths depend on the transport parameters (and thus on the size) of solutes. Effective blood flow, which may be related to the exchange of the solute between blood and dialysate, is defined using an analogy to the extraction/absorption coefficients for blood-tissue exchange. Various approximations for the distributed model formula for diffusive mass transport coefficient (K(BD)) are possible. The appropriate range for their application is obtained from the general formula.

  3. Highly repressible expression system for cloning genes that specify potentially toxic proteins.

    PubMed Central

    O'Connor, C D; Timmis, K N

    1987-01-01

    A highly repressible expression vector system that allows the cloning of potentially deleterious genes has been constructed. Undesired expression of a cloned gene was prevented (i) at the level of initiation of transcription, by the presence of the strong but highly repressible leftward promoter of bacteriophage lambda, lambda pL, and (ii) at the level of transcript elongation or translation, through synthesis of antisense RNA complementary to the mRNA of the cloned gene. The system was tested by measuring the inhibition of expression of traT, the gene for the TraT major outer membrane lipoprotein. Direct detection and functional assays indicated that an essentially complete inhibition of traT expression was obtained. As a further test of the system, the gene encoding the EcoRI restriction endonuclease was cloned in the absence of the gene of the corresponding protective EcoRI modification methylase. Transformants harboring this construct were only viable when both repression controls were operational. Images PMID:2443481

  4. Significance of the evolutionary α1,3-galactosyltransferase (GGTA1) gene inactivation in preventing extinction of apes and old world monkeys.

    PubMed

    Galili, Uri

    2015-01-01

    The α1,3-galactosyltransferase (α1,3GT or GGTA1) gene displays unique evolutionary characteristics. This gene appeared early in mammalian evolution and is absent in other vertebrates. The α1,3GT gene is active in marsupials, nonprimate placental mammals, lemurs (prosimians) and New World monkeys, encoding the α1,3GT enzyme that synthesizes a carbohydrate antigen called "α-gal epitope." The α-gal epitope is present in large numbers on cell membrane glycolipids and glycoproteins. The α1,3GT gene was inactivated in ancestral Old World monkeys and apes by frameshift single-base deletions forming premature stop codons. Because of this gene inactivation, humans, apes, and Old World monkeys lack α-gal epitopes and naturally produce an antibody called the "anti-Gal antibody" which binds specifically to α-gal epitopes and which is the most abundant antibody in humans. The evolutionary event that resulted in the inactivation of the α1,3GT gene in ancestral Old World primates could have been mediated by a pathogen endemic to Eurasia-Africa landmass that exerted pressure for selection of primate populations lacking the α-gal epitope. Once the α-gal epitope was eliminated, primates could produce the anti-Gal antibody, possibly as means of defense against pathogens expressing this epitope. This assumption is supported by the fossil record demonstrating an almost complete extinction of apes in the late Miocene and failure of Old World monkeys to radiate into multiple species before that period. A present outcome of this evolutionary event is the anti-Gal-mediated rejection of mammalian xenografts expressing α-gal epitopes in humans, apes, and Old World monkeys.

  5. The in vitro and in vivo biocompatibility evaluation of electrospun recombinant spider silk protein/PCL/gelatin for small caliber vascular tissue engineering scaffolds.

    PubMed

    Xiang, Ping; Wang, Shan-Shan; He, Meng; Han, Yong-He; Zhou, Zhi-Hua; Chen, Deng-Long; Li, Min; Ma, Lena Q

    2018-03-01

    Recombinant spider silk protein (pNSR32) and gelatin (Gt) were demonstrated to enhance cytocompatibility of electrospun pNSR32/PCL/Gt scaffold. However, its potential pro-inflammatory effects and interactions with tissue and blood are unknown. In this study, the physicochemical properties and in vitro and in vivo biocompatibility of such scaffolds were evaluated. The results showed that the pNSR32/PCL/Gt scaffold possessed larger average fiber diameters, wider fiber diameter distribution and faster degradation rate than that of pNSR32/PCL and PCL scaffolds. The addition of pNSR32 and Gt had little influence on the hemolysis and plasma re-calcification time, but prolonged kinetic clotting time and reduced the platelet adhesion. The Il-6 and Tnf-α mRNA expression levels were up-regulated in macrophages seeded on the PCL and pNSR32/PCL scaffolds. The lowest release of IL-6 and TNF-α appeared in the pNSR32/PCL/Gt scaffold. Histological results revealed that the PCL and pNSR32/PCL scaffolds elicited severe host tissue responses after implantation, while prominent ingrowth of host cells were observed in the pNSR32/PCL and pNSR32/PCL/Gt scaffolds. The comet assay and bone marrow micronucleus test demonstrated that the pNSR32/PCL/Gt scaffold did not increase the frequency of DNA damage or bone marrow micronucleus. In short, this study confirmed that the pNSR32/PCL/Gt scaffold exhibited better blood and tissue compatibility than pNSR32/PCL and PCL scaffolds. No induction of genotoxicity and inflammatory factor releases makes the pNSR32/PCL/Gt scaffold a good candidate for engineering small diameter vascular tissue. Copyright © 2017. Published by Elsevier B.V.

  6. Nebulization with Gamma-Tocopherol Ameliorates Acute Lung Injury after Burn and Smoke Inhalation in the Ovine Model

    PubMed Central

    Yamamoto, Yusuke; Enkhbaatar, Perenlei; Sousse, Linda E.; Sakurai, Hiroyuki; Rehberg, Sebastian W.; Asmussen, Sven; Kraft, Edward R.; Wright, Charlotte L.; Bartha, Eva; Cox, Robert A.; Hawkins, Hal K.; Traber, Lillian D.; Traber, Maret G.; Szabo, Csaba; Herndon, David N.; Traber, Daniel L.

    2012-01-01

    We hypothesize that the nebulization of gamma-tocopherol (g-T) in the airway of our ovine model of acute respiratory distress syndrome (ARDS) will effectively improve pulmonary function following burn and smoke inhalation after 96 hours. Adult ewes (n=14) were subjected to 40% total body surface area burn and were insufflated with 48 breaths of cotton smoke under deep anesthesia, in a double-blind comparative study. A customized aerosolization device continuously delivered g-T in ethanol with each breath from 3 to 48 hours after the injury (g-T group, n=6), while the control group (n=5) was nebulized with only ethanol. Animals were weaned from the ventilator when possible. All animals were sacrificed after 96 hours, with the exception of one untreated animal that was euthanized after 64 hours. Lung g-T concentration significantly increased after g-T nebulization compared to the control group (38.5±16.8 nmol/g vs. 0.39±0.46, p<0.01). The PaO2/FiO2 ratio was significantly higher after treatment with g-T compared to the control group (310±152 vs 150±27.0, p<0.05). The following clinical parameters were improved with g-T treatment: pulmonary shunt fraction, peak and pause pressures, lung bloodless wet-to-dry weight ratios (2.9±0.87 vs 4.6±1.4, p<0.05), and bronchiolar obstruction (2.0±1.1% vs 4.6±1.7%, p<0.05). Nebulization of g-T, carried by ethanol, improved pulmonary oxygenation and markedly reduced the time necessary for assisted ventilation in burn and smoke injured sheep. Delivery of g-T into the lungs may be a safe, novel, and efficient approach for management of ALI patients who have sustained oxidative damage to the airway. PMID:22266978

  7. Label-Free Quantitative Proteomic Analysis of Harmless and Pathogenic Strains of Infectious Microalgae, Prototheca spp.

    PubMed Central

    Murugaiyan, Jayaseelan; Eravci, Murat; Weise, Christoph; Roesler, Uwe

    2016-01-01

    Microalgae of the genus Prototheca (P.) spp are associated with rare algal infections of invertebrates termed protothecosis. Among the seven generally accepted species, P. zopfii genotype 2 (GT2) is associated with a severe form of bovine mastitis while P. blaschkeae causes the mild and sub-clinical form of mastitis. The reason behind the infectious nature of P. zopfii GT2, while genotype 1 (GT1) remains non-infectious, is not known. Therefore, in the present study we investigated the protein expression level difference between the genotypes of P. zopfii and P. blaschkeae. Cells were cultured to the mid-exponential phase, harvested, and processed for LC-MS analysis. Peptide data was acquired on an LTQ Orbitrap Velos, raw spectra were quantitatively analyzed with MaxQuant software and matching with the reference database of Chlorella variabilis and Auxenochlorella protothecoides resulted in the identification of 226 proteins. Comparison of an environmental strain with infectious strains resulted in the identification of 51 differentially expressed proteins related to carbohydrate metabolism, energy production and protein translation. The expression level of Hsp70 proteins and their role in the infectious process is worth further investigation. All mass spectrometry data are available via ProteomeXchange with identifier PXD005305. PMID:28036087

  8. Two-stage continuous operation of recombinant Escherichia coli using the bacteriophage lambda Q- vector.

    PubMed

    Oh, Jeong Seok; Cho, Daechul; Park, Tai Hyun

    2005-11-01

    A two-stage continuous culture of Escherichia coli in combination with a bacteriophage lambda system was performed in order to overcome the intrinsic plasmid instability that is frequently observed in recombinant fermentation. A phage lambda vector with a Q(-) mutation was used to enhance the expression of the lambda system. The optimal values of the important operational variables such as the substrate concentration, the dilution rate, and the mean residence time on the expression of the cloned gene were determined in both batch and continuous cultures. For all culturing modes, the full induction of the cloned gene was observed 4 h after the temperature shift. In the two stage continuous culture, the overproduction reached their maxima at D=0.25 h(-1) with 1.5 S(0) of the medium supply. The maximum productivity of the total beta-galactosidase was 16.3x10(6) U l(-1) h(-1), which was approximately seven times higher than that in the single-copy lysogenic stage. The recombinant cells were stable in the lysogenic state for more than 260 h, while they were stable for 40 h in the lytic state. The instability that developed rapidly in the second tank is believed to be due to the accumulation of lysis proteins as a result of vector leakage during the operation.

  9. Stream Channel Stability. Appendix J. Numerical Model for Routing Graded Sediments in Alluvial Channels,

    DTIC Science & Technology

    1981-04-01

    expressed as volume of dry sediment per unit length of channel. RHB Hydraulic radius. ft SCAP(IF) Potential transport capacity of ft 3/ft material...GO) TO iSO I6=0 DO 104 IC=i,INL IA=IC+ICST-IS IF(KI(I)EQOORI(ICI).E.Q(IC2))GO TO 105 L PROPAGATION OF SHOCK WAVE AA=(QI(IC,i)/KIN)**BET AAF=AA+QL*DTS...KSI(IC).GT.0) GO Tn £09 IF(IA.EQ.i) GO TO 140 IF(XC(IA).L.E.XC(IA-i)) GO TO 11.0 C NO SHOCK IS FORMED 140 KSC(IA)=0 CO TO 104 C SHOCK IS FORMED 110

  10. Interaction between the phage HK022 Nun protein and the nut RNA of phage lambda.

    PubMed

    Chattopadhyay, S; Hung, S C; Stuart, A C; Palmer, A G; Garcia-Mena, J; Das, A; Gottesman, M E

    1995-12-19

    The nun gene product of prophage HK022 excludes phage lambda infection by blocking the expression of genes downstream from the lambda nut sequence. The Nun protein functions both by competing with lambda N transcription-antitermination protein and by actively inducing transcription termination on the lambda chromosome. We demonstrate that Nun binds directly to a stem-loop structure within nut RNA, boxB, which is also the target for the N antiterminator. The two proteins show comparable affinities for boxB and they compete with each other. Their interactions with boxB are similar, as shown by RNase protection experiments, NMR spectroscopy, and analysis of boxB mutants. Each protein binds the 5' strand of the boxB stem and the adjacent loop. The stem does not melt upon the binding of Nun or N, as the 3' strand remains sensitive to a double-strand-specific RNase. The binding of RNA partially protects Nun from proteolysis and changes its NMR spectra. Evidently, although Nun and N bind to the same surface of boxB RNA, their respective complexes interact differently with RNA polymerase, inducing transcription termination or antitermination, respectively.

  11. The effect of maternal diabetes on the Wnt-PCP pathway during embryogenesis as reflected in the developing mouse eye.

    PubMed

    López-Escobar, Beatriz; Cano, David A; Rojas, Anabel; de Felipe, Beatriz; Palma, Francisco; Sánchez-Alcázar, José A; Henderson, Deborah; Ybot-González, Patricia

    2015-02-01

    Embryopathies that develop as a consequence of maternal diabetes have been studied intensely in both experimental and clinical scenarios. Accordingly, hyperglycaemia has been shown to downregulate the expression of elements in the non-canonical Wnt-PCP pathway, such as the Dishevelled-associated activator of morphogenesis 1 (Daam1) and Vangl2. Daam1 is a formin that is essential for actin polymerization and for cytoskeletal reorganization, and it is expressed strongly in certain organs during mouse development, including the eye, neural tube and heart. Daam1(gt/gt) and Daam1(gt/+) embryos develop ocular defects (anophthalmia or microphthalmia) that are similar to those detected as a result of hyperglycaemia. Indeed, studying the effects of maternal diabetes on the Wnt-PCP pathway demonstrated that there was strong association with the Daam1 genotype, whereby the embryopathy observed in Daam1(gt/+) mutant embryos of diabetic dams was more severe. There was evidence that embryonic exposure to glucose in vitro diminishes the expression of genes in the Wnt-PCP pathway, leading to altered cytoskeletal organization, cell shape and cell polarity in the optic vesicle. Hence, the Wnt-PCP pathway appears to influence cell morphology and cell polarity, events that drive the cellular movements required for optic vesicle formation and that, in turn, are required to maintain the fate determination. Here, we demonstrate that the Wnt-PCP pathway is involved in the early stages of mouse eye development and that it is altered by diabetes, provoking the ocular phenotype observed in the affected embryos. © 2015. Published by The Company of Biologists Ltd.

  12. Shedding light on serpent sight: the visual pigments of henophidian snakes.

    PubMed

    Davies, Wayne L; Cowing, Jill A; Bowmaker, James K; Carvalho, Livia S; Gower, David J; Hunt, David M

    2009-06-10

    The biologist Gordon Walls proposed his "transmutation" theory through the 1930s and the 1940s to explain cone-like morphology of rods (and vice versa) in the duplex retinas of modern-day reptiles, with snakes regarded as the epitome of his hypothesis. Despite Walls' interest, the visual system of reptiles, and in particular snakes, has been widely neglected in favor of studies of fishes and mammals. By analyzing the visual pigments of two henophidian snakes, Xenopeltis unicolor and Python regius, we show that both species express two cone opsins, an ultraviolet-sensitive short-wavelength-sensitive 1 (SWS1) (lambda(max) = 361 nm) pigment and a long-wavelength-sensitive (LWS) (lambda(max) = 550 nm) pigment, providing the potential for dichromatic color vision. They also possess rod photoreceptors which express the usual rod opsin (Rh1) pigment with a lambda(max) at 497 nm. This is the first molecular study of the visual pigments expressed in the photoreceptors of any snake species. The presence of a duplex retina and the characterization of LWS, SWS1, and Rh1 visual pigments in henophidian snakes implies that "lower" snakes do not provide support for Walls' transmutation theory, unlike some "higher" (caenophidian) snakes and other reptiles, such as geckos. More data from other snake lineages will be required to test this hypothesis further.

  13. Molecular epidemiology of Escherichia coli O157:H7 strains by bacteriophage lambda restriction fragment length polymorphism analysis: application to a multistate foodborne outbreak and a day-care center cluster.

    PubMed

    Samadpour, M; Grimm, L M; Desai, B; Alfi, D; Ongerth, J E; Tarr, P I

    1993-12-01

    Genomic DNAs prepared from 168 isolates of Escherichia coli O157:H7 were analyzed for restriction fragment length polymorphisms on Southern blots probed with bacteriophage lambda DNA. The isolates analyzed included strains from a recent large multistate outbreak of E. coli O157:H7 infection associated with consumption of poorly cooked beef in restaurants, a day-care center cluster, and temporally and geographically unrelated isolates. E. coli O157:H7 isolates recovered from the incriminated meat and from 61 (96.8%) of 63 patients from Washington and Nevada possessed identical lambda restriction fragment length patterns. The lambda restriction fragment length polymorphisms observed in 11 (91.7%) of 12 day-care center patients were identical, but they differed from that of the strain associated with the multistate outbreak. E. coli O157:H7 from 42 patients temporally or geographically unrelated to either cluster of infection possessed unique and different lambda restriction fragment length patterns, except for paired isolates from three separate clusters of infection. These data demonstrate that the hybridization of DNA digests of E. coli O157:H7 with radiolabelled bacteriophage lambda DNA can be a useful, stable, and discriminatory epidemiologic tool for analyzing the linkage between strains of E. coli O157:H7.

  14. [The role of BDNF pathway in lambda-cyhalothrin disrupting the promotion of 17β-Estradiol on Post-synaptic Density 95 protein expression in HT22 cell].

    PubMed

    Li, N; Wang, Q N; Wu, D J; Yang, C W; Luo, B B

    2016-07-20

    Objective: To explore the effect of BDNF pathway on lambda-cyhalothrin interfering estrogen promoting the expression of PSD95 in hippocampus neurons. Methods: HT22 cell line were used to, treating with lambda-cyhalothrin (LCT, 50 μmol/L) , 17β-Estradiol (E2, 10 nmol/L) , LCT (50 μmol/L) +TrkB FC (20 μg/ml) , E2 (10 nmol/L) +TrkB FC (20 μg/ml) , LCT (50 μmol/L) +ICI182 780 (1 μmol/L) , E2 (10 nmol/L) + ICI182 780 (1 μmol/L) , LCT (50 μmol/L) +E2 (10 nmol/L) for 24 h. MTT kit was used to detect cell viability. Post-synaptic Density 95 protein expression was measured by western blot. ELISA assay was used to detect the level of brain derived neurotrophic factor (BDNF) of culture supernatant and cell. Results: Campared to Sham, LCT or E2 could promote the expression of PSD95 LCT+ICI could reduce the expresion of BDNF ( P <0.05) , campared to LCT, LCT+TrkB FC could reduce the expression of PSD95 and LCT+ICI cound reduce the expresion of BDNF ( P <0.05) , campared to E2, E2+TrkB FC could reduce the expression of PSD95 and E 2 +ICI could reduce the expression of BDNF ( P <0.05) , campared to E2, LCT+ E2 could reduce the expression of PSD95 and BDNF ( P <0.05) . Conclusion: BDNF pathway plays a key role in E2 promoting the expression of PSD95 in neural cells. Although LCT alone has a similar effect on E2. LCT could disrupt the promotion of E2 on PSD95 expression via BDNF pathway.

  15. [Vitamin para-aminobenzoic acid inhibits development of SOS function in tif-1 mutants of Escherichia coli at nonpermissive temperatures].

    PubMed

    Vasil'eva, S V; Gorb, T E; Rapoport, I A

    1983-12-01

    The development of "SOS" inducible functions in lysogenic and non-lysogenic strains of Escherichia coli tif-1 sfiA11 (lambda) at nonpermissive temperature of 42 degrees C was strongly suppressed by para-aminobenzoic acid (PABA). The rate of prophage lambda induction decreased 400 times, as compared to the control level; the efficiency of W-reactivation of UV-irradiated phage lambda decreased 37.5 to 16%. PABA also inhibited to some extent (1.5 times) the process of inducible recombination on the RecF pathway. The processes of spontaneous lambda induction and W-reactivation, as well as spontaneous recombination on RecBC and RecF pathways, were not influenced by PABA. The above data are in accordance with previous studies of PABA action when the manifestation of "SOS" functions was induced by chemical mutagens. The action of PABA has been tentatively interpreted on the basis of negative control of "SOS" repair pathway.

  16. GEMINI-TITAN (GT)-11 - PREFLIGHT PREP - CHECKOUT - CAPE

    NASA Image and Video Library

    1966-07-21

    S66-47635 (21 July 1966) --- McDonnell Aircraft Corporation personnel bolt the Gemini-11 spacecraft to a support ring for bore sighting in the Pyrotechnic Installation Building, Merritt Island, during checkout and preflight preparations at the Kennedy Space Center. Photo credit: NASA

  17. Fate of the insecticide lambda-cyhalothrin in ditch enclosures differing in vegetation density.

    PubMed

    Leistra, Minze; Zweers, Anton J; Warinton, Jacqui S; Crum, Steven J H; Hand, Laurence H; Beltman, Wim H J; Maund, Stephen J

    2004-01-01

    Use of the insecticide lambda-cyhalothrin in agriculture may result in the contamination of water bodies, for example by spray drift. Therefore, the possible exposure of aquatic organisms to this insecticide needs to be evaluated. The exposure of the organisms may be reduced by the strong sorption of the insecticide to organic materials and its susceptibility to hydrolysis at the high pH values in the natural range. In experiments done in May and August, formulated lambda-cyhalothrin was mixed with the water body of enclosures in experimental ditches containing a bottom layer and macrophytes (at different densities) or phytoplankton. Concentrations of lambda-cyhalothrin in the water body and in the sediment layer, and contents in the plant compartment, were measured by gas-liquid chromatography at various times up to 1 week after application. Various water quality parameters were also measured. Concentrations of lambda-cyhalothrin decreased rapidly in the water column: 1 day after application, 24-40% of the dose remained in the water, and by 3 days it had declined to 1.8-6.5%. At the highest plant density, lambda-cyhalothrin residue in the plant compartment reached a maximum of 50% of the dose after 1 day; at intermediate and low plant densities, this maximum was only 3-11% of the dose (after 1-2 days). The percentage of the insecticide in the ditch sediment was 12% or less of the dose and tended to be lower at higher plant densities. Alkaline hydrolysis in the water near the surface of macrophytes and phytoplankton is considered to be the main dissipation process for lambda-cyhalothrin.

  18. Analysis of HIV disease burden by calculating the percentages of patients with CD4 counts <100 cells/µL across 52 districts reveals hot spots for intensified commitment to programmatic support.

    PubMed

    Coetzee, Lindi Marie; Cassim, Naseem; Glencross, Deborah Kim

    2017-05-24

    South Africa (SA)'s Comprehensive HIV and AIDS Care, Management and Treatment (CCMT) programme has reduced new HIV infections and HIV-related deaths. In spite of progress made, 11.2% of South Africans (4.02 million) were living with HIV in 2015. The National Health Laboratory Service (NHLS) in SA performs CD4 testing in support of the CCMT programme and collates data through the NHLS Corporate Data Warehouse. The objective of this study was to assess the distribution of CD4 counts <100 cells/µL (defining severely immunosuppressed HIV-positive patients) and >500 cells/µL (as an HIV-positive 'wellness' indicator). CD4 data were extracted for the financial years 2010/11 and 2014/15, according to the district where the test was ordered, for predefined CD4 ranges. National and provincial averages of CD4 counts <100 and >500 cells/µL were calculated. Data were analysed using Stata 12 and mapping was done with ArcGIS software, reporting percentages of CD4 counts <100 and >500 cells/µL by district. The national average percentage of patients with CD4 counts <100 cells/µL showed a marked decrease (by 22%) over the 5-year study period, with a concurrent increase in CD4 counts >500 cells/µL (by 57%). District-by-district analysis showed that in 2010/11, 44/52 districts had >10% of CD4 samples with counts <100 cells/µL, decreasing to only 17/52 districts by 2014/15. Overall, districts in the Western Cape and KwaZulu-Natal had the lowest percentages of CD4 counts <100 cells/µL, as well as the highest percentages of counts >500 cells/µL. In contrast, in 2014/15, the highest percentages of CD4 counts <100 cells/µL were noted in the West Rand (Gauteng), Vhembe (Limpopo) and Nelson Mandela Bay (Eastern Cape) districts, where the lowest percentages of counts >500 cells/µL were also noted. The percentages of CD4 counts <100 cells/µL highlighted here reveal districts with positive change suggestive of programmatic improvements, and also highlight districts requiring local interventions to achieve the UNAIDS/SA National Department of Health 90-90-90 HIV treatment goals. The study further underscores the value of using NHLS laboratory data, an underutilised national resource, to leverage laboratory test data to enable a more comprehensive understanding of programme-specific health indicators.

  19. Action Mechanism of Chamaecyparis obtusa Oil on Hair Growth

    PubMed Central

    Park, Young-Ok; Kim, Su-Eun; Kim, Young-Chul

    2013-01-01

    This study was carried out to examine the action mechanism of Chamaecyparis obtusa oil (CO) on hair growth in C57BL/6 mice. For alkaline phosphatase (ALP) and γ-glutamyl transpeptidase (γ-GT) activities in the skin tissue, at week 4, the 3% minoxidil (MXD) and 3% CO treatment groups showed an ALP activity that was significantly higher by 85% (p < 0.001) and 48% (p < 0.05) and an γ-GT activity that was significantly higher by 294% (p < 0.01) and 254% (p < 0.05) respectively, as compared to the saline (SA) treatment group. For insulin-like growth factor-1 (IGF-1) mRNA expression in the skin tissue, at week 4, the MXD and CO groups showed a significantly higher expression by 204% (p < 0.05) and 426% (p < 0.01) respectively, as compared to the SA group. At week 4, vascular endothelial growth factor (VEGF) expression in the MXD and CO groups showed a significantly higher expression by 74% and 96% (p < 0.05) respectively, however, epidermal growth factor (EGF) expression in the MXD and CO groups showed a significantly lower expression by 66% and 61% (p < 0.05) respectively, as compared to the SA group. Stem cell factor (SCF) expression in the MXD and CO groups was observed by immunohistochemistry as significant in a part of the bulge around the hair follicle and in a part of the basal layer of the epidermis. Taking all the results together, on the basis of effects on ALP and γ-GT activity, and the expression of IGF-1, VEGF and SCF, which are related to the promotion of hair growth, it can be concluded that CO induced a proliferation and division of hair follicle cells and maintained the anagen phase. Because EGF expression was decreased significantly, CO could delay the transition to the catagen phase. PMID:24578794

  20. Autosomal dominant hypoparathyroidism caused by germline mutation in GNA11: phenotypic and molecular characterization.

    PubMed

    Li, Dong; Opas, Evan E; Tuluc, Florin; Metzger, Daniel L; Hou, Cuiping; Hakonarson, Hakon; Levine, Michael A

    2014-09-01

    Most cases of autosomal dominant hypoparathyroidism (ADH) are caused by gain-of-function mutations in CASR or dominant inhibitor mutations in GCM2 or PTH. Our objectives were to identify the genetic basis for ADH in a multigenerational family and define the underlying disease mechanism. Here we evaluated a multigenerational family with ADH in which affected subjects had normal sequences in these genes and were shorter than unaffected family members. We collected clinical and biochemical data from 6 of 11 affected subjects and performed whole-exome sequence analysis on DNA from two affected sisters and their affected father. Functional studies were performed after expression of wild-type and mutant Gα11 proteins in human embryonic kidney-293-CaR cells that stably express calcium-sensing receptors. Whole-exome-sequencing followed by Sanger sequencing revealed a heterozygous mutation, c.179G>T; p.R60L, in GNA11, which encodes the α-subunit of G11, the principal heterotrimeric G protein that couples calcium-sensing receptors to signal activation in parathyroid cells. Functional studies of Gα11 R60L showed increased accumulation of intracellular concentration of free calcium in response to extracellular concentration of free calcium with a significantly decreased EC50 compared with wild-type Gα11. By contrast, R60L was significantly less effective than the oncogenic Q209L form of Gα11 as an activator of the MAPK pathway. Compared to subjects with CASR mutations, patients with GNA11 mutations lacked hypercalciuria and had normal serum magnesium levels. Our findings indicate that the germline gain-of-function mutation of GNA11 is a cause of ADH and implicate a novel role for GNA11 in skeletal growth.

  1. Autosomal Dominant Hypoparathyroidism Caused by Germline Mutation in GNA11: Phenotypic and Molecular Characterization

    PubMed Central

    Li, Dong; Opas, Evan E.; Tuluc, Florin; Metzger, Daniel L.; Hou, Cuiping; Hakonarson, Hakon

    2014-01-01

    Context: Most cases of autosomal dominant hypoparathyroidism (ADH) are caused by gain-of-function mutations in CASR or dominant inhibitor mutations in GCM2 or PTH. Objective: Our objectives were to identify the genetic basis for ADH in a multigenerational family and define the underlying disease mechanism. Subjects: Here we evaluated a multigenerational family with ADH in which affected subjects had normal sequences in these genes and were shorter than unaffected family members. Methods: We collected clinical and biochemical data from 6 of 11 affected subjects and performed whole-exome sequence analysis on DNA from two affected sisters and their affected father. Functional studies were performed after expression of wild-type and mutant Gα11 proteins in human embryonic kidney-293-CaR cells that stably express calcium-sensing receptors. Results: Whole-exome-sequencing followed by Sanger sequencing revealed a heterozygous mutation, c.179G>T; p.R60L, in GNA11, which encodes the α-subunit of G11, the principal heterotrimeric G protein that couples calcium-sensing receptors to signal activation in parathyroid cells. Functional studies of Gα11 R60L showed increased accumulation of intracellular concentration of free calcium in response to extracellular concentration of free calcium with a significantly decreased EC50 compared with wild-type Gα11. By contrast, R60L was significantly less effective than the oncogenic Q209L form of Gα11 as an activator of the MAPK pathway. Compared to subjects with CASR mutations, patients with GNA11 mutations lacked hypercalciuria and had normal serum magnesium levels. Conclusions: Our findings indicate that the germline gain-of-function mutation of GNA11 is a cause of ADH and implicate a novel role for GNA11 in skeletal growth. PMID:24823460

  2. Note on the practical significance of the Drazin inverse

    NASA Technical Reports Server (NTRS)

    Wilkinson, J. H.

    1979-01-01

    The solution of the differential system Bx = Ax + f where A and B are n x n matrices, and A - Lambda B is not a singular pencil, may be expressed in terms of the Drazin inverse. It is shown that there is a simple reduced form for the pencil A - Lambda B which is adequate for the determination of the general solution and that although the Drazin inverse could be determined efficiently from this reduced form it is inadvisable to do so.

  3. Asymptotic structure of space-time with a positive cosmological constant

    NASA Astrophysics Data System (ADS)

    Kesavan, Aruna

    In general relativity a satisfactory framework for describing isolated systems exists when the cosmological constant Lambda is zero. The detailed analysis of the asymptotic structure of the gravitational field, which constitutes the framework of asymptotic flatness, lays the foundation for research in diverse areas in gravitational science. However, the framework is incomplete in two respects. First, asymptotic flatness provides well-defined expressions for physical observables such as energy and momentum as 'charges' of asymptotic symmetries at null infinity, [special character omitted] +. But the asymptotic symmetry group, called the Bondi-Metzner-Sachs group is infinite-dimensional and a tensorial expression for the 'charge' integral of an arbitrary BMS element is missing. We address this issue by providing a charge formula which is a 2-sphere integral over fields local to the 2-sphere and refers to no extraneous structure. The second, and more significant shortcoming is that observations have established that Lambda is not zero but positive in our universe. Can the framework describing isolated systems and their gravitational radiation be extended to incorporate this fact? In this dissertation we show that, unfortunately, the standard framework does not extend from the Lambda = 0 case to the Lambda > 0 case in a physically useful manner. In particular, we do not have an invariant notion of gravitational waves in the non-linear regime, nor an analog of the Bondi 'news tensor', nor positive energy theorems. In addition, we argue that the stronger boundary condition of conformal flatness of intrinsic metric on [special character omitted]+, which reduces the asymptotic symmetry group from Diff([special character omitted]) to the de Sitter group, is insufficient to characterize gravitational fluxes and is physically unreasonable. To obtain guidance for the full non-linear theory with Lambda > 0, linearized gravitational waves in de Sitter space-time are analyzed in detail. i) We show explicitly that conformal flatness of the boundary removes half the degrees of freedom of the gravitational field by hand and is not justified by physical considerations; ii) We obtain gauge invariant expressions of energy-momentum and angular momentum fluxes carried by gravitational waves in terms of fields defined at [special character omitted]+; iii) We demonstrate that the flux formulas reduce to the familiar ones in Minkowski spacetime in spite of the fact that the limit Lambda → 0 is discontinuous (since, in particular, [special character omitted]+ changes its space-like character to null in the limit); iv) We obtain a generalization of Einstein's 1918 quadrupole formula for power emission by a linearized source to include a positive Lambda; and, finally v) We show that, although energy of linearized gravitational waves can be arbitrarily negative in general, gravitational waves emitted by physically reasonable sources carry positive energy.

  4. Gyrator transform of Gaussian beams with phase difference and generation of hollow beam

    NASA Astrophysics Data System (ADS)

    Xiao, Zhiyu; Xia, Hui; Yu, Tao; Xie, Ding; Xie, Wenke

    2018-03-01

    The optical expression of Gaussian beams with phase difference, which is caused by gyrator transform (GT), has been obtained. The intensity and phase distribution of transform Gaussian beams are analyzed. It is found that the circular hollow vortex beam can be obtained by overlapping two GT Gaussian beams with π phase difference. The effect of parameters on the intensity and phase distributions of the hollow vortex beam are discussed. The results show that the shape of intensity distribution is significantly influenced by GT angle α and propagation distance z. The size of the hollow vortex beam can be adjusted by waist width ω 0. Compared with previously reported results, the work shows that the hollow vortex beam can be obtained without any model conversion of the light source.

  5. Gyrator transform of Gaussian beams with phase difference and generation of hollow beam

    NASA Astrophysics Data System (ADS)

    Xiao, Zhiyu; Xia, Hui; Yu, Tao; Xie, Ding; Xie, Wenke

    2018-06-01

    The optical expression of Gaussian beams with phase difference, which is caused by gyrator transform (GT), has been obtained. The intensity and phase distribution of transform Gaussian beams are analyzed. It is found that the circular hollow vortex beam can be obtained by overlapping two GT Gaussian beams with π phase difference. The effect of parameters on the intensity and phase distributions of the hollow vortex beam are discussed. The results show that the shape of intensity distribution is significantly influenced by GT angle α and propagation distance z. The size of the hollow vortex beam can be adjusted by waist width ω 0. Compared with previously reported results, the work shows that the hollow vortex beam can be obtained without any model conversion of the light source.

  6. Comparative proteomic analysis in Aphis glycines Mutsumura under lambda-cyhalothrin insecticide stress.

    PubMed

    Bi, Rui; Pan, Yiou; Shang, Qingli; Peng, Tianfei; Yang, Shuang; Wang, Shang; Xin, Xuecheng; Liu, Yan; Xi, Jinghui

    2016-09-01

    Lambda-cyhalothrin is now widely used in China to control the soybean aphid Aphis glycines. To dissect the resistance mechanism, a laboratory-selected resistant soybean aphid strain (CRR) was established with a 43.42-fold resistance ratio to λ-cyhalothrin than the susceptible strain (CSS) in adult aphids. In this study, a comparative proteomic analysis between the CRR and CSS strains revealed important differences between the susceptible and resistant strains of soybean aphids for λ-cyhalothrin. Approximately 493 protein spots were detected in two-dimensional polyacrylamide gel electrophoresis (2-DE). Thirty-six protein spots displayed differential expression of >2-fold in the CRR strain compared to the CSS strain. Out of these 36 protein spots, 21 had elevated and 15 had decreased expression. Twenty-four differentially expressed proteins were identified by MALDI TOF MS/MS and categorized into the functional groups cytoskeleton-related protein, carbohydrate and energy metabolism, protein folding, antioxidant system, and nucleotide and amino acid metabolism. Function analysis showed that cytoskeleton-related proteins and energy metabolism proteins have been associated with the λ-cyhalothrin resistance of A. glycines. The differential expression of λ-cyhalothrin responsive proteins reflected the overall change in cellular structure and metabolism after insecticide treatment in aphids. In summary, our studies improve understanding of the molecular mechanism resistance of soybean aphid to lambda-cyhalothrin, which will facilitate the development of rational approaches to improve the management of this pest and to improve the yield of soybean. Copyright © 2016. Published by Elsevier Inc.

  7. Disruption of a Spermatogenic Cell-Specific Mouse Enolase 4 (Eno4) Gene Causes Sperm Structural Defects and Male Infertility1

    PubMed Central

    Nakamura, Noriko; Dai, Qunsheng; Williams, Jason; Goulding, Eugenia H.; Willis, William D.; Brown, Paula R.; Eddy, Edward M.

    2013-01-01

    ABSTRACT Sperm utilize glycolysis to generate ATP required for motility, and several spermatogenic cell-specific glycolytic isozymes are associated with the fibrous sheath (FS) in the principal piece of the sperm flagellum. We used proteomics and molecular biology approaches to confirm earlier reports that a novel enolase is present in mouse sperm. We then found that a pan-enolase antibody, but not antibodies to ENO2 and ENO3, recognized a protein in the principal piece of the mouse sperm flagellum. Database analyses identified two previously uncharacterized enolase family-like candidate genes, 64306537H0Rik and Gm5506. Northern analysis indicated that 64306537H0Rik (renamed Eno4) was transcribed in testes of mice by Postnatal Day 12. To determine the role of ENO4, we generated mice using embryonic stem cells in which an Eno4 allele was disrupted by a gene trap containing a beta galactosidase (beta-gal) reporter (Eno4+/Gt). Expression of beta-gal occurred in the testis, and male mice homozygous for the gene trap allele (Eno4Gt/Gt) were infertile. Epididymal sperm numbers were 2-fold lower and sperm motility was reduced substantially in Eno4Gt/Gt mice compared to wild-type mice. Sperm from Eno4Gt/Gt mice had a coiled flagellum and a disorganized FS. The Gm5506 gene encodes a protein identical to ENO1 and also is transcribed at a low level in testis. We conclude that ENO4 is required for normal assembly of the FS and provides most of the enolase activity in sperm and that Eno1 and/or Gm5506 may encode a minor portion of the enolase activity in sperm. PMID:23446454

  8. Proteomic analyses reveal the key roles of BrlA and AbaA in biogenesis of gliotoxin in Aspergillus fumigatus.

    PubMed

    Shin, Kwang-Soo; Kim, Young Hwan; Yu, Jae-Hyuk

    2015-07-31

    The opportunistic human pathogenic fungus Aspergillus fumigatus primarily reproduces by forming a large number of asexual spores (conidia). Sequential activation of the central regulators BrlA, AbaA and WetA is necessary for the fungus to undergo asexual development. In this study, to address the presumed roles of these key developmental regulators during proliferation of the fungus, we analyzed and compared the proteomes of vegetative cells of wild type (WT) and individual mutant strains. Approximately 1300 protein spots were detectable from 2-D electrophoresis gels. Among these, 13 proteins exhibiting significantly altered accumulation levels were further identified by ESI-MS/MS. Markedly, we found that the GliM and GliT proteins associated with gliotoxin (GT) biosynthesis and self-protection of the fungus from GT were significantly down-regulated in the ΔabaA and ΔbrlA mutants. Moreover, mRNA levels of other GT biosynthetic genes including gliM, gliP, gliT, and gliZ were significantly reduced in both mutant strains, and no and low levels of GT were detectable in the ΔbrlA and ΔabaA mutant strains, respectively. As GliT is required for the protection of the fungus from GT, growth of the ΔbrlA mutant with reduced levels of GliT was severely impaired by exogenous GT. Our studies demonstrate that AbaA and BrlA positively regulate expression of the GT biosynthetic gene cluster in actively growing vegetative cells, and likely bridge morphological and chemical development during the life-cycle of A. fumigatus. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Association of heme oxygenase-1 GT-repeat polymorphism with blood pressure phenotypes and its relevance to future cardiovascular mortality risk: an observation based on arsenic-exposed individuals.

    PubMed

    Wu, Meei-Maan; Chiou, Hung-Yi; Chen, Chi-Ling; Hsu, Ling-I; Lien, Li-Ming; Wang, Chih-Hao; Hsieh, Yi-Chen; Wang, Yuan-Hung; Hsueh, Yu-Mei; Lee, Te-Chang; Cheng, Wen-Fang; Chen, Chien-Jen

    2011-12-01

    Heme oxygenase (HO)-1 is up-regulated as a cellular defense responding to stressful stimuli in experimental studies. A GT-repeat length polymorphism in the HO-1 gene promoter was inversely correlated to HO-1 induction. Here, we reported the association of GT-repeat polymorphism with blood pressure (BP) phenotypes, and their interaction on cardiovascular (CV) mortality risk in arsenic-exposed cohorts. Associations of GT-repeat polymorphism with BP phenotypes were investigated at baseline in a cross-sectional design. Effect of GT-repeat polymorphism on CV mortality was investigated in a longitudinal design stratified by hypertension. GT-repeat variants were grouped by S (<27 repeats) or L (≥ 27 repeats) alleles. Multivariate analyses were used to estimate the effect size after accounting for CV covariates. Totally, 894 participants were recruited and analyzed. At baseline, carriers with HO-1 S alleles had lower diastolic BP (L/S genotypes, P = 0.014) and a lower possibility of being hypertensive (L/S genotypes, P = 0.048). After follow-up, HO-1 S allele was significantly associated with a reduced CV risk in hypertensive participants [relative mortality ratio (RMR) 0.27 (CI 0.11, 0.69), P = 0.007] but not in normotensive. Hypertensive participants without carrying the S allele had a 5.23-fold increased risk [RMR 5.23 (CI 1.99, 13.69), P = 0.0008] of CV mortality compared with normotensive carrying the S alleles. HO-1 short GT-repeat polymorphism may play a protective role in BP regulation and CV mortality risk in hypertensive individuals against environmental stressors. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. Removal of arsenic in flotation of galena and sphalerite

    NASA Astrophysics Data System (ADS)

    Yu, Dae-hwan; Kim, Min-kyu; Han, Oh-hyung; Park, Chul-hyun

    2017-04-01

    In Korea, Janggun mine that produces the concentrate of galena (PbS) /sphalerite (ZnS) containing arsenic of 1.3% charges a penalty of US 3/ton to LS-Nikko smelter. Hence in this work, flotation tests for removal of arsenopyrite (FeAsS) from sulfide minerals were carried out using lab scale flotation cell, which maintain grade and recovery of PbS and ZnS in comparison to flotation plant. Particularly, this study was focused on investigating the combination of several chemical reagents such as depressant, collector, activator and etc. that affect flotation performance. In the straight differential flotation for PbS, a PbS grade of 67.80% and a recovery of 80.2% could be obtained with FeAsS removal of 84.1% (0.2% As) under the conditions of 20% feed solids concentration, pH 8.5, 50g/t frother (AF65), 50g/t collector (AP242) and 600g/t As depressant (NaHSO3) and 600g/t Zn depressant (ZnSO4). In the ZnS flotation, the maximum separation achievable for ZnS has been shown to be a grade of 50.27% and a recovery of 88.7%. At this time, FeAsS removal of 87.8% (0.16% As) could be successfully accomplished under pH 11, and 1.2kg/t Zn activator (CuSO4), 100g/t frother (AF65), 100g/t collector (AP211) and 400g/t As depressant (NaHSO3). Acknowledgments This work was supported by the Energy and Resources Engineering Program Grant funded by the Ministry of Trade, Industry and Energy, Korea

  11. GEMINI-TITAN (GT)-11 - EARTH SKY - OUTER SPACE

    NASA Image and Video Library

    1966-09-14

    S66-54643 (14 Sept. 1966) --- Western half of Australia, including the coastline from Perth to Port Darwin, looking west, as seen from the Gemini-11 spacecraft at a record-high apogee of 740 nautical miles during its 26th revolution of Earth. Photo credit: NASA

  12. A single amino acid substitution in the variable region of the light chain specifically blocks immunoglobulin secretion.

    PubMed Central

    Dul, J L; Argon, Y

    1990-01-01

    Although immunoglobulin light chains are usually secreted in association with heavy chains, free light chains can be secreted by lymphocytes. To identify the structural features of light chains that are essential for their secretion, we mutated a conserved sequence in the variable domain of a lambda I light chain. The effects of the mutations on secretion were assayed by transient expression in COS-1 cells. One mutant (AV60), which replaced Ala-60 with Val, was secreted as efficiently as wild-type lambda I by transfected COS-1 cells. This result was not surprising because secreted lambda II chains contain valine in this position. However, a second lambda I mutant (AV60FS62), which replaced Phe-62 with Ser as well as Ala-60 with Val, was not secreted. This mutant was arrested in the endoplasmic reticulum, as judged by immunofluorescence and by its association with a lumenal endoplasmic reticulum protein, immunoglobulin heavy chain binding protein (BiP). The defect in secretion was not due to gross misfolding of the lambda I chain, since cells cotransfected with AV60FS62 and an immunoglobulin heavy chain gene produced functional antigen-binding antibodies. These assembled IgM molecules were still not secreted. Hence, the replacement of Phe-62 with Ser specifically affects a determinant on the lambda I light chain that is necessary for the intracellular transport of this molecule. Images PMID:2122454

  13. Removal of arsenopyrite from complex sulfide minerals by froth flotation

    NASA Astrophysics Data System (ADS)

    Choi, Jin-young; Kim, Yang-soo; Kim, Dong-gyu; Han, Oh-hyung; Park, Chul-hyun

    2016-04-01

    Arsenic (As) is one of hazardous materials and a penalty element in metal concentrates and so metal concentrates containing arsenic of over 0.5% has been currently restricted in import and export trade. It also corrodes a smelting furnace as well as shortens its life cycle. In korea, Janggun mine that produces galena (PbS) /sphalerite (ZnS) concentrate containing arsenic of 1.78% charges a penalty of US 2/ton to LS-Nikko smelter. Hence in this work, flotation tests for removal of arsenopyrite (FeAsS) from sulfide mineral concentrates were carried out using lab scale flotation cell, which maintain grade and recovery of PbS and ZnS in comparison to flotation plant. Particularly, this study was focused on investigating the combination of several chemical reagents (depressant, collector, activator and etc.) that affect flotation performance. In the straight differential flotation for PbS, a PbS grade of 75.80% and a recovery of 90.12% could be obtained with FeAsS removal of 84.1% (0.2% As) under the conditions of 20% feed solids concentration, pH 8.5, 50g/t frother (AF65), 40g/t collector (AP242) and 800g/t As depressant (NaHSO3) and 600g/t Zn depressant (ZnSO4). In the ZnS flotation, the maximum separation achievable for ZnS using froth flotation has been shown to be a grade of 72.57% and a recovery of 95.43%. At this time, FeAsS removal of 87.8% (0.16% As) could be successfully accomplished under pH 11, and 800g/t Zn activator (CuSO4), 75g/t frother (AF65), 60g/t collector (AP211) and 600g/t As depressant (NaHSO3). Acknowledgments This work was supported by the Energy and Resources Engineering Program Grant funded by the Ministry of Trade, Industry and Energy, Korea

  14. Mouse model for deficiency of methionine synthase reductase exhibits short-term memory impairment and disturbances in brain choline metabolism.

    PubMed

    Jadavji, Nafisa M; Bahous, Renata H; Deng, Liyuan; Malysheva, Olga; Grand'maison, Marilyn; Bedell, Barry J; Caudill, Marie A; Rozen, Rima

    2014-07-15

    Hyperhomocysteinaemia can contribute to cognitive impairment and brain atrophy. MTRR (methionine synthase reductase) activates methionine synthase, which catalyses homocysteine remethylation to methionine. Severe MTRR deficiency results in homocystinuria with cognitive and motor impairments. An MTRR polymorphism may influence homocysteine levels and reproductive outcomes. The goal of the present study was to determine whether mild hyperhomocysteinaemia affects neurological function in a mouse model with Mtrr deficiency. Mtrr+/+, Mtrr+/gt and Mtrrgt/gt mice (3 months old) were assessed for short-term memory, brain volumes and hippocampal morphology. We also measured DNA methylation, apoptosis, neurogenesis, choline metabolites and expression of ChAT (choline acetyltransferase) and AChE (acetylcholinesterase) in the hippocampus. Mtrrgt/gt mice exhibited short-term memory impairment on two tasks. They had global DNA hypomethylation and decreased choline, betaine and acetylcholine levels. Expression of ChAT and AChE was increased and decreased respectively. At 3 weeks of age, they showed increased neurogenesis. In the cerebellum, mutant mice had DNA hypomethylation, decreased choline and increased expression of ChAT. Our work demonstrates that mild hyperhomocysteinaemia is associated with memory impairment. We propose a mechanism whereby a deficiency in methionine synthesis leads to hypomethylation and compensatory disturbances in choline metabolism in the hippocampus. This disturbance affects the levels of acetylcholine, a critical neurotransmitter in learning and memory.

  15. Probability weighted moments: Definition and relation to parameters of several distributions expressable in inverse form

    USGS Publications Warehouse

    Greenwood, J. Arthur; Landwehr, J. Maciunas; Matalas, N.C.; Wallis, J.R.

    1979-01-01

    Distributions whose inverse forms are explicitly defined, such as Tukey's lambda, may present problems in deriving their parameters by more conventional means. Probability weighted moments are introduced and shown to be potentially useful in expressing the parameters of these distributions.

  16. Neutrino-nucleus reactions based on recent structure studies

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

    Suzuki, Toshio; National Astronomical Observatory of Japan, Mitaka, Tokyo 181-8588

    2015-05-15

    Neutrino-nucleus reactions are studied with the use of new shell model Hamiltonians, which have proper tensor components in the interactions and prove to be successful in the description of Gamow-Teller (GT) strengths in nuclei. The new Hamiltonians are applied to obtain new neutrino-nucleus reaction cross sections in {sup 12}C, {sup 13}C, {sup 56}Fe and {sup 56}Ni induced by solar and supernova neutrinos. The element synthesis by neutrino processes in supernova explosions is discussed with the new cross sections. The enhancement of the production yields of {sup 7}Li, {sup 11}B and {sup 55}Mn is obtained while fragmented GT strength in {supmore » 56}Ni with two-peak structure is found to result in smaller e-capture rates at stellar environments. The monopole-based universal interaction with tensor force of π+ρ meson exchanges is used to evaluate GT strength in {sup 40}Ar and ν-induced reactions on {sup 40}Ar. It is found to reproduce well the experimental GT strength in {sup 40}Ar.« less

  17. Hematopoiesis In The Equine Fetal Liver Suggests Immune Preparedness

    PubMed Central

    Battista, JM; Tallmadge, RL; Stokol, T; Felippe, MJB

    2014-01-01

    We investigated how the equine fetus prepares its pre-immune humoral repertoire for an imminent exposure to pathogens in the neonatal period, particularly how the primary hematopoietic organs are equipped to support B cell hematopoiesis and immunoglobulin (Ig) diversity. We demonstrated that the liver and the bone marrow at approximately 100 days of gestation (DG) are active sites of hematopoiesis based on the expression of signature mRNA (c-KIT, CD34, IL7R, CXCL12, IRF8, PU.1, PAX5, NOTCH1, GATA1, CEBPA) and protein markers (CD34, CD19, IgM, CD3, CD4, CD5, CD8, CD11b, CD172A) of hematopoietic development and leukocyte differentiation molecules, respectively. To verify Ig diversity achieved during the production of B cells, V(D)J segments were sequenced in primary lymphoid organs of the equine fetus and adult horse, revealing that similar heavy chain VDJ segments and CDR3 lengths were most frequently used independent of life stage. In contrast, different lambda light chain segments were predominant in equine fetal compared to adult stage and, surprisingly, the fetus had less restricted use of variable gene segments to construct the lambda chain. Fetal Igs also contained elements of sequence diversity, albeit to a smaller degree than that of the adult horse. Our data suggest that the B cells produced in the liver and bone marrow of the equine fetus generate a wide repertoire of pre-immune Igs for protection, and the more diverse use of different lambda variable gene segments in fetal life may provide the neonate an opportunity to respond to a wider range of antigens at birth. PMID:25179685

  18. Nucleic acid immunization protects dogs against challenge with virulent canine parvovirus.

    PubMed

    Jiang, W; Baker, H J; Swango, L J; Schorr, J; Self, M J; Smith, B F

    1998-04-01

    Nucleic acid vaccines (NAVs) use expression vectors encoding one or more antigen genes to transfect host cells inducing both humoral and cellular immunity against the expressed antigen. NAV offers major advantages over conventional vaccines for the protection of humans and animals. This study shows that a plasmid DNA (pGT36VP1) encoding the full length VP1 region of canine parvovirus (CPV) induces immunity that protects dogs against challenge with virulent virus. Five dogs without anti-CPV antibodies were injected at 9 months of age with increasing doses of pGT36VP1 or saline. NAV vaccinated dogs showed an increase of serum IgG titer starting 1 week post-injection which peaked at week 2 and remained detectable for at least 14 weeks. A second dose of NAV resulted in an anamnestic response within 1 week. IgG titers peaked at week 3 and 4 after the second injection. All pGT36VP1 vaccinated dogs were protected against infection after virulent CPV challenge regardless of dose and the unvaccinated control dog was fully susceptible. This study demonstrated for the first time that a NAV can protect dogs against an infectious disease.

  19. 75 FR 70229 - Combined Notice of Filings No. 2

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-17

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Combined Notice of Filings No. 2... Storage Company submits tariff section 6.11.11- GT&C North American Energy Standards Board, v.3.0 etc., to...-001. Applicants: National Grid LNG, LP. Description: National Grid LNG, LP submits tariff filing per...

  20. GEMINI-TITAN (GT)-11 - EARTH SKY - OUTER SPACE

    NASA Image and Video Library

    1966-09-14

    S66-54548 (12-15 Sept. 1966) --- This photograph, taken during one of the 44 orbits the Gemini-11 crew made around Earth, shows the Indian Ocean west of Australia looking northwest. The crew consisted of astronauts Charles Conrad Jr. and Richard F. Gordon Jr. Photo credit: NASA

  1. Family values in the age of genomics: comparative analyses of temperate bacteriophage HK022.

    PubMed

    Weisberg, R A; Gottesmann, M E; Hendrix, R W; Little, J W

    1999-01-01

    HK022 is a temperate coliphage related to phage lambda. Its chromosome has been completely sequenced, and several aspects of its life cycle have been intensively studied. In the overall arrangement, expression, and function of most of its genes, HK022 broadly resembles lambda and other members of the lambda family. Upon closer view, significant differences emerge. The differences reveal alternative strategies used by related phages to cope with similar problems and illuminate previously unknown regulatory and structural motifs. HK022 prophages protect lysogens from superinfection by producing a sequence-specific RNA binding protein that prematurely terminates nascent transcripts of infecting phage. It uses a novel RNA-based mechanism to antiterminate its own early transcription. The HK022 protein shell is strengthened by a complex pattern of covalent subunit interlinking to form a unitary structure that resembles chain-mail armour. Its integrase and repressor proteins are similar to those of lambda, but the differences provide insights into the evolution of biological specificity and the elements needed for construction of a stable genetic switch.

  2. Large magnetic penetration depth and thermal fluctuations in a superconducting Ca10(Pt3As8)[(Fe1 xPtx)2As2]5 (x = 0.097) single crystal

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

    Kim J.; Nazaretski E.; Ronning, F.

    2012-05-18

    We have measured the temperature dependence of the absolute value of the magnetic penetration depth {lambda}(T) in a Ca{sub 10}(Pt{sub 3}As{sub 8})[(Fe{sub 1-x}Pt{sub x}){sub 2}As{sub 2}]{sub 5} (x = 0.097) single crystal using a low-temperature magnetic force microscope (MFM). We obtain {lambda}{sub ab}(0) {approx} 1000 nm via extrapolating the data to T = 0. This large {lambda} and pronounced anisotropy in this system are responsible for large thermal fluctuations and the presence of a liquid vortex phase in this low-temperature superconductor with a critical temperature of 11 K, consistent with the interpretation of the electrical transport data. The superconducting parametersmore » obtained from {lambda} and coherence length {zeta} place this compound in the extreme type II regime. Meissner responses (via MFM) at different locations across the sample are similar to each other, indicating good homogeneity of the superconducting state on a submicron scale.« less

  3. New primordial-magnetic-field limit from the latest LIGO S5 data

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

    Wang, S.

    Since the energy momentum tensor of a magnetic field always contains a spin-2 component in its anisotropic stress, stochastic primordial magnetic field (PMF) in the early universe must generate stochastic gravitational-wave (GW) background. This process will greatly affect the relic gravitational wave (RGW), which is one of the major scientific goals of the laser interferometer GW detections. Recently, the fifth science (S5) run of laser interferometer gravitational-wave observatory (LIGO) gave a latest upper limit {Omega}{sub GW}<6.9x10{sup -6} on the RGW background. Utilizing this upper limit, we derive new PMF limits: for a scale of galactic cluster {lambda}=1 Mpc, the amplitudemore » of PMF, that produced by the electroweak phase transition, has to be weaker than B{sub {lambda}{<=}4}x10{sup -7} G; for a scale of supercluster {lambda}=100 Mpc, the amplitude of PMF has to be weaker than B{sub {lambda}{<=}9}x10{sup -11} G. In this manner, GW observation has potential to make interesting contributions to the study of primordial magnetic field.« less

  4. Human placenta: relative content of antibodies of different classes and subclasses (IgG1-IgG4) containing lambda- and kappa-light chains and chimeric lambda-kappa-immunoglobulins.

    PubMed

    Lekchnov, Evgenii A; Sedykh, Sergey E; Dmitrenok, Pavel S; Buneva, Valentina N; Nevinsky, Georgy A

    2015-06-01

    The specific organ placenta is much more than a filter: it is an organ that protects, feeds and regulates the growth of the embryo. Affinity chromatography, ELISA, SDS-PAGE and matrix-assisted laser desorption ionization mass spectrometry were used. Using 10 intact human placentas deprived of blood, a quantitative analysis of average relative content [% of total immunoglobulins (Igs)] was carried out for the first time: (92.7), IgA (2.4), IgM (2.5), kappa-antibodies (51.4), lambda-antibodies (48.6), IgG1 (47.0), IgG2 (39.5), IgG3 (8.8) and IgG4 (4.3). It was shown for the first time that placenta contains sIgA (2.5%). In the classic paradigm, Igs represent products of clonal B-cell populations, each producing antibodies recognizing a single antigen. There is a common belief that IgGs in mammalian biological fluids are monovalent molecules having stable structures and two identical antigen-binding sites. However, similarly to human milk Igs, placenta antibodies undergo extensive half-molecule exchange and the IgG pool consists of 43.5 ± 15.0% kappa-kappa-IgGs and 41.6 ± 17.0% lambda-lambda-IgGs, while 15.0 ± 4.0% of the IgGs contained both kappa- and lambda-light chains. Kappa-kappa-IgGs and lambda-lambda-IgGs contained, respectively (%): IgG1 (47.7 and 34.4), IgG2 (36.3 and 44.5), IgG3 (7.4 and 11.8) and IgG4 (7.5 and 9.1), while chimeric kappa-lambda-IgGs consisted of (%): 43.5 IgG1, 41.0 IgG2, 5.6 IgG3 and 7.9 IgG4. Our data are indicative of the possibility of half-molecule exchange between placenta IgGs of various subclasses, raised against different antigens, which explains a very well-known polyspecificity and cross-reactivity of different human IgGs. © The Japanese Society for Immunology. 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Transient and Prolonged Response of Chicken Cecum Mucosa to Colonization with Different Gut Microbiota

    PubMed Central

    Volf, Jiri; Polansky, Ondrej; Varmuzova, Karolina; Gerzova, Lenka; Sekelova, Zuzana; Faldynova, Marcela; Babak, Vladimir; Medvecky, Matej; Smith, Adrian L.; Kaspers, Bernd; Velge, Philippe; Rychlik, Ivan

    2016-01-01

    In this study we determined protein and gene expression in the caeca of newly hatched chickens inoculated with cecal contents sourced from hens of different ages. Over 250 proteins exhibited modified expression levels in response to microbiota inoculation. The most significant inductions were observed for ISG12-2, OASL, ES1, LYG2, DMBT1-L, CDD, ANGPTL6, B2M, CUZD1, IgM and Ig lambda chain. Of these, ISG12-2, ES1 and both immunoglobulins were expressed at lower levels in germ-free chickens compared to conventional chickens. In contrast, CELA2A, BRT-2, ALDH1A1, ADH1C, AKR1B1L, HEXB, ALDH2, ALDOB, CALB1 and TTR were expressed at lower levels following inoculation of microbiota. When chicks were given microbiota preparations from different age donors, the recipients mounted differential responses to the inoculation which also differed from the response profile in naturally colonised birds. For example, B2M, CUZD1 and CELA2A responded differently to the inoculation with microbiota of 4- or 40-week-old hens. The increased or decreased gene expression could be recorded 6 weeks after the inoculation of newly hatched chickens. To characterise the proteins that may directly interact with the microbiota we characterised chicken proteins that co-purified with the microbiota and identified a range of host proteins including CDD, ANGPTL6, DMBT1-L, MEP1A and Ig lambda. We propose that induction of ISG12-2 results in reduced apoptosis of host cells exposed to the colonizing commensal microbiota and that CDD, ANGPTL6, DMBT1-L, MEP1A and Ig lambda reduce contact of luminal microbiota with the gut epithelium thereby reducing the inflammatory response. PMID:27685470

  6. A novel homozygous mutation IVS6+5G>T in CYP11B1 gene in a Vietnamese patient with 11β-hydroxylase deficiency.

    PubMed

    Nguyen, Thi Phuong Mai; Nguyen, Thu Hien; Ngo, Diem Ngoc; Vu, Chi Dung; Nguyen, Thi Kim Lien; Nong, Van Hai; Nguyen, Huy Hoang

    2015-07-10

    Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease which is characterized by a deficiency of one of the enzymes involved in the synthesis of cortisol from cholesterol by the adrenal cortex. CAH cases arising from impaired 11β-hydroxylase are the second most common form. Mutations in the CYP11B1 gene are the cause of 11β-hydroxylase deficiency. This study was performed on a patient with congenital adrenal hyperplasia and with premature development such as enlarged penis, muscle development, high blood pressure, and bone age equivalent of 5 years old at 2 years of chronological age. Biochemical tests for steroids confirmed the diagnosis of CAH. We used PCR and sequencing to screen for mutations in CYP11B1 gene. Results showed that the patient has a novel homozygous mutation of guanine (G) to thymine (T) in intron 6 (IVS6+5G>T). The analysis of this mutation by MaxEntScan boundary software indicated that this mutant could affect the gene splicing during transcription. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Purification of bacteriophage lambda repressor

    PubMed Central

    Gao, Ning; Shearwin, Keith; Mack, John; Finzi, Laura; Dunlap, David

    2013-01-01

    Bacteriophage lambda repressor controls the lysogeny/lytic growth switch after infection of E. coli by lambda phage. In order to study in detail the looping of DNA mediated by the protein, tag-free repressor and a loss-of-cooperativity mutant were expressed in E.coli and purified by (1) ammonium sulfate fractionation, (2) anion-exchange chromatography and (3) heparin affinity chromatography. This method employs more recently developed and readily available chromatography resins to produce highly pure protein in good yield. In tethered particle motion looping assays and atomic force microscopy “footprinting” assays, both the wild-type protein and a C-terminal His-tagged variant, purified using immobilized metal affinity chromatography, bound specifically to high affinity sites to mediate loop formation. In contrast the G147D loss-of-cooperativity mutant bound specifically but did not secure loops. PMID:23831434

  8. Emission of a pulsed purely rotational transition chemical H{sub 2}-F{sub 2} laser

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

    Molevich, N E; Pichugin, S Yu

    2008-04-30

    The possibility of obtaining efficient emission at purely rotational transitions of HF molecules in a pulsed chemical hydrogen fluoride laser is studied theoretically. The operation of a H{sub 2}-F{sub 2} laser with a gas pressure of 1.1 atm emitting at the v, j {yields} v, j - 1 (v = 1 - 6, j = 10 - 14) transitions is simulated taking into account resonance VR processes. The total specific laser energy release calculated over all the vibrational levels is 5.5 J L{sup -1} on purely rotational transitions at {lambda}{approx}17 {mu}m (j = 14), 3.5 J L{sup -1} at {lambda}{approx}18.5more » {mu}m (j = 13), and 2.5 J L{sup -1} at {lambda}{approx}20 {mu}m (j = 12). (lasers and amplifiers)« less

  9. Coronography with a dynamic hologram

    NASA Astrophysics Data System (ADS)

    Ricci, D.; Le Coroller, H.; Piron, P.

    2010-10-01

    An innovative solution to improve the performances of coronagraphs consists in adding, in the optical scheme, a dynamic hologram removing most of the residual speckle starlight. Our simulations show that the detection limit in the flux ratio between a host star and a very near planet, in the case of wavefront bumpiness imperfections at lambda/20 (resp. lambda/100), improves over a factor 1000 (resp. 10000) when equipped with a hologram, allowing to direct image an exo-Earth at a distance of 11 parsec with a ∼6.5m space telescope.

  10. Liver enzymes and risk of diabetes and cardiovascular disease: results of the Firenze Bagno a Ripoli (FIBAR) study.

    PubMed

    Monami, Matteo; Bardini, Gianluca; Lamanna, Caterina; Pala, Laura; Cresci, Barbara; Francesconi, Paolo; Buiatti, Eva; Rotella, Carlo M; Mannucci, Edoardo

    2008-03-01

    The aim of the study was to assess gamma-glutamyl transpeptidase (gamma-GT), alanine aminotransferase, and aspartate aminotransferase (AST) in the prediction of diabetes and cardiovascular disease (CVD) in subjects free from hepatic diseases other than nonalcoholic fatty liver disease. The present analysis was performed on the cohort of subjects enrolled in the Firenze Bagno a Ripoli (FIBAR) study, a screening program for diabetes performed between 1 March 2001 and 31 December 2003 in the city of Florence on 3124 subjects who underwent an oral glucose tolerance test. Incident cases of diabetes in nondiabetic subjects (n = 2662) were obtained through databases of drug prescriptions, hospital admissions, and lists of subjects eligible for reimbursement. Incident CVD in subjects free of diabetes and CVD at enrollment (n = 2617) was identified through hospital admissions and through the register of causes of death. Mean follow-up was 39.6 +/- 12.0 months and 39.8 +/- 11.4 months for diabetes and CVD, respectively. Yearly incidence of diabetes and CVD was 0.4% and 0.2%, respectively. After adjustment for age and sex, gamma-GT >40 U/L was associated with increased incidence of diabetes and CVD (hazard ratio [95% confidence interval]: 2.54 [1.26-5.11], P < .05 and 2.21 [0.98-5.43], P < .10, respectively). Risk of diabetes, but not of CVD, was increased in patients with gamma-GT in the 25- to 40-U/L range. After adjustment for confounders, AST >40 U/L predicted CVD (hazard ratio, 6.5 [95% confidence interval, 1.5-28.1]), but not diabetes. Elevated gamma-GT or AST is an independent predictor of CVD. An increase of gamma-GT levels above the reference range, or also in the upper reference range, is an independent predictor of incident diabetes.

  11. JNK pathway activation is controlled by Tao/TAOK3 to modulate ethanol sensitivity.

    PubMed

    Kapfhamer, David; King, Ian; Zou, Mimi E; Lim, Jana P; Heberlein, Ulrike; Wolf, Fred W

    2012-01-01

    Neuronal signal transduction by the JNK MAP kinase pathway is altered by a broad array of stimuli including exposure to the widely abused drug ethanol, but the behavioral relevance and the regulation of JNK signaling is unclear. Here we demonstrate that JNK signaling functions downstream of the Sterile20 kinase family gene tao/Taok3 to regulate the behavioral effects of acute ethanol exposure in both the fruit fly Drosophila and mice. In flies tao is required in neurons to promote sensitivity to the locomotor stimulant effects of acute ethanol exposure and to establish specific brain structures. Reduced expression of key JNK pathway genes substantially rescued the structural and behavioral phenotypes of tao mutants. Decreasing and increasing JNK pathway activity resulted in increased and decreased sensitivity to the locomotor stimulant properties of acute ethanol exposure, respectively. Further, JNK expression in a limited pattern of neurons that included brain regions implicated in ethanol responses was sufficient to restore normal behavior. Mice heterozygous for a disrupted allele of the homologous Taok3 gene (Taok3Gt) were resistant to the acute sedative effects of ethanol. JNK activity was constitutively increased in brains of Taok3Gt/+ mice, and acute induction of phospho-JNK in brain tissue by ethanol was occluded in Taok3Gt/+ mice. Finally, acute administration of a JNK inhibitor conferred resistance to the sedative effects of ethanol in wild-type but not Taok3Gt/+ mice. Taken together, these data support a role of a TAO/TAOK3-JNK neuronal signaling pathway in regulating sensitivity to acute ethanol exposure in flies and in mice.

  12. Investigating energy deposition within cell populations using Monte Carlo simulations.

    PubMed

    Oliver, Patricia A K; Thomson, Rowan M

    2018-06-27

    In this work, we develop multicellular models of healthy and cancerous human soft tissues, which are used to investigate energy deposition in subcellular targets, quantify the microdosimetric spread in a population of cells, and determine how these results depend on model details. Monte Carlo (MC) tissue models combining varying levels of detail on different length scales are developed: microscopically-detailed regions of interest (>1500 explicitly-modelled cells) are embedded in bulk tissue phantoms irradiated by photons (20 keV to 1.25 MeV). Specific energy (<i>z</i>; energy imparted per unit mass) is scored in nuclei and cytoplasm compartments using the EGSnrc user-code egs_chamber; specific energy mean, <<i>z</i>>, standard deviation, <i>σ</i><sub><i>z</i></sub>, and distribution, <i>f</i>(<i>z</i>,<i>D</i>), are calculated for a variety of macroscopic doses, <i>D</i>. MC-calculated <i>f</i>(<i>z</i>,<i>D</i>) are compared with normal distributions having the same mean and standard deviation. For mGy doses, there is considerable variation in energy deposition (microdosimetric spread) throughout a cell population: <i>e</i>.<i>g</i>., for 30 keV photons irradiating melanoma with 7.5 μm cell radius and 3 μm nuclear radius, <i>σ</i><sub><i>z</i></sub>/<<i>z</i>> for nuclear targets is 170%, and the fraction of nuclei receiving no energy deposition, <i>f</i><sub><i>z</i>=0</sub>, is 0.31 for a dose of 10 mGy. If cobalt-60 photons are considered instead, then <i>σ</i><sub><i>z</i></sub>/<<i>z</i>> decreases to 84%, and <i>f</i><sub><i>z</i>=0</sub> decreases to 0.036. These results correspond to randomly arranged cells with cell/nucleus sizes randomly sampled from a normal distribution with a standard deviation of 1 μm. If cells are arranged in a hexagonal lattice and cell/nucleus sizes are uniform throughout the population, then <i>σ</i><sub><i>z</i></sub>/<<i>z</i>> decreases to 106% and 68% for 30 keV and cobalt-60,respectively; <i>f</i><sub><i>z</i>=0</sub> decreases to 0.25 and 0.00094 for 30 keV and cobalt-60, respectively. Thus, specific energy distributions are sensitive to cell/nucleus sizes and their distributions: variations in specific energy deposited over a cell population are underestimated if targets are assumed to be uniform in size compared with more realistic variation in target size. Bulk tissue dose differs from <<i>z</i>> for nuclei (cytoplasms) by up to 21% (12%) across all cell/nucleus sizes, bulk tissues, and incident photon energies, considering a 50 mGy dose level. Overall, results demonstrate the importance of microdosimetric considerations at low doses, and indicate the sensitivity of energy deposition within subcellular targets to incident photon energy, dose level, elemental compositions, and microscopic tissue model. © 2018 Institute of Physics and Engineering in Medicine.

  13. Tissue-specific Requirements of β-Catenin in External Genitalia Development

    PubMed Central

    Lin, Congxing; Yin, Yan; Long, Fanxin; Ma, Liang

    2008-01-01

    SUMMARY External genitalia are body appendages specialized for internal fertilization. Its development can be divided into two phases, an early androgen-independent phase and a late androgen-dependant sexual differentiation phase. In the early phase, the embryonic anlage of external genitalia, the genital tubercle (GT), are morphologically identical in both sexes. Although congenital external genitalia malformations represent the second most common birth defect in humans, the genetic pathways governing early external genitalia development and urethra formation are poorly understood. Proper development of the GT requires coordinated outgrowth of the mesodermally-derived mesenchyme and extension of the endodermal urethra within an ectodermal epithelial capsule. Here we demonstrate that β-Catenin plays indispensable and distinct roles in each of the aforementioned three tissue layers in early androgen-independent GT development. WNT-β-Catenin signaling is required in the endodermal urethra to activate and maintain Fgf8 expression and direct GT outgrowth, as well as to maintain homeostasis of the urethra. Moreover, β-Catenin is required in the mesenchyme to promote cell proliferation. In contrast, β-Catenin is required in the ectoderm to maintain tissue integrity possibly through cell-cell adhesion during GT outgrowth. The fact that both endodermal and ectodermal β-Catenin knockout animals develop severe hypospadias in both sexes raises the possibility that deregulation of any of these functions can contribute to the etiology of congenital external genital defects in humans. PMID:18635608

  14. Thermal annealing and pressure effects on BaFe2-xCoxAs2 single crystals.

    PubMed

    Shin, Dongwon; Jung, Soon-Gil; Prathiba, G; Seo, Soonbeom; Choi, Ki-Young; Kim, Kee Hoon; Park, Tuson

    2017-11-26

    We investigate the pressure and thermal annealing effects on BaFe<sub>2-<i>x</i></sub>Co<sub><i>x</i></sub>As<sub>2</sub> (Co-Ba122) single crystals with <i>x</i> = 0.1 and 0.17 via electrical transport measurements. The thermal annealing treatment not only enhances the superconducting transition temperature (<i>T</i><sub>c</sub>) from 9.6 to 12.7 K for <i>x</i> = 0.1 and from 18.1 to 21.0 K for <i>x</i> = 0.17, but also increases the antiferromagnetic transition temperature (<i>T</i><sub>N</sub>). Simultaneous enhancement of <i>T</i><sub>c</sub> and <i>T</i><sub>N</sub> by the thermal annealing treatment indicates that thermal annealing could substantially improve the quality of the Co-doped Ba122 samples. Interestingly, <i>T</i><sub>c</sub> of the Co-Ba122 compounds shows a scaling behavior with a linear dependence on the resistivity value at 290 K, irrespective of tuning parameters, such as chemical doping, pressure, and thermal annealing. These results not only provide an effective way to access the intrinsic properties of the BaFe<sub>2</sub>As<sub>2</sub> system, but also may shed a light on designing new materials with higher superconducting transition temperature. © 2017 IOP Publishing Ltd.

  15. Transferring elements of a density matrix

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

    Allahverdyan, Armen E.; Hovhannisyan, Karen V.; Yerevan State University, A. Manoogian Street 1, Yerevan

    2010-01-15

    We study restrictions imposed by quantum mechanics on the process of matrix-element transfer. This problem is at the core of quantum measurements and state transfer. Given two systems A and B with initial density matrices lambda and r, respectively, we consider interactions that lead to transferring certain matrix elements of unknown lambda into those of the final state r-tilde of B. We find that this process eliminates the memory on the transferred (or certain other) matrix elements from the final state of A. If one diagonal matrix element is transferred, r(tilde sign){sub aa}=lambda{sub aa}, the memory on each nondiagonal elementmore » lambda{sub an}ot ={sub b} is completely eliminated from the final density operator of A. Consider the following three quantities, Relambda{sub an}ot ={sub b}, Imlambda{sub an}ot ={sub b}, and lambda{sub aa}-lambda{sub bb} (the real and imaginary part of a nondiagonal element and the corresponding difference between diagonal elements). Transferring one of them, e.g., Rer(tilde sign){sub an}ot ={sub b}=Relambda{sub an}ot ={sub b}, erases the memory on two others from the final state of A. Generalization of these setups to a finite-accuracy transfer brings in a trade-off between the accuracy and the amount of preserved memory. This trade-off is expressed via system-independent uncertainty relations that account for local aspects of the accuracy-disturbance trade-off in quantum measurements. Thus, the general aspect of state disturbance in quantum measurements is elimination of memory on non-diagonal elements, rather than diagonalization.« less

  16. Effects of Low Phytanic Acid-Concentrated DHA on Activated Microglial Cells: Comparison with a Standard Phytanic Acid-Concentrated DHA.

    PubMed

    Ruiz-Roso, María Belén; Olivares-Álvaro, Elena; Quintela, José Carlos; Ballesteros, Sandra; Espinosa-Parrilla, Juan F; Ruiz-Roso, Baltasar; Lahera, Vicente; de Las Heras, Natalia; Martín-Fernández, Beatriz

    2018-05-30

    Docosahexaenoic acid (DHA, 22:6 n-3) is an essential omega-3 (ω-3) long chain polyunsaturated fatty acid of neuronal membranes involved in normal growth, development, and function. DHA has been proposed to reduce deleterious effects in neurodegenerative processes. Even though, some inconsistencies in findings from clinical and pre-clinical studies with DHA could be attributed to the presence of phytanic acid (PhA) in standard DHA treatments. Thus, the aim of our study was to analyze and compare the effects of a low PhA-concentrated DHA with a standard PhA-concentrated DHA under different neurotoxic conditions in BV-2 activated microglial cells. To this end, mouse microglial BV-2 cells were stimulated with either lipopolysaccharide (LPS) or hydrogen peroxide (H 2 O 2 ) and co-incubated with DHA 50 ppm of PhA (DHA (PhA:50)) or DHA 500 ppm of PhA (DHA (PhA:500)). Cell viability, superoxide anion (O 2 - ) production, Interleukin 6 (L-6), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), glutathione peroxidase (GtPx), glutathione reductase (GtRd), Caspase-3, and the brain-derived neurotrophic factor (BDNF) protein expression were explored. Low PhA-concentrated DHA protected against LPS or H 2 O 2 -induced cell viability reduction in BV-2 activated cells and O 2 - production reduction compared to DHA (PhA:500). Low PhA-concentrated DHA also decreased COX-2, IL-6, iNOS, GtPx, GtRd, and SOD-1 protein expression when compared to DHA (PhA:500). Furthermore, low PhA-concentrated DHA increased BDNF protein expression in comparison to DHA (PhA:500). The study provides data supporting the beneficial effect of low PhA-concentrated DHA in neurotoxic injury when compared to a standard PhA-concentrated DHA in activated microglia.

  17. Temporally and spatially restricted expression of a gland cell gene during regeneration and in vitro transdifferentiation in the hydrozoan Podocoryne carnea.

    PubMed

    Baader, C D; Schuchert, P; Schmid, V; Heiermann, Reinhard; Plickert, Günter

    1995-01-01

    An antiserum to transdifferentiated striated muscle cells from the medusa of Podocoryne carnea was prepared and used to screen a λ gt11-expression library prepared from gonozoids of P. carnea. We isolated a cDNA clone termed Pod-EPPT with at least 63 tandem repeats of the tetrapeptide-motive glu-pro-pro-thr, named Pod-EPPT. Using Pod-EPPT as a molecular marker for head quality the morphological relationship between the two metagenic life stages of this hydroid, the polyp and the medusa, was studied. In situ hybridization demonstrated that expression of the gene corresponding is restricted to secretory cells in the endoderm of the oral hypostome region of polyps and medusae and, presumably, to progenitor cells of this type. Cells expressing Pod-EPPT could not be observed in the larval stage. During head regeneration in polyps, Pod-EPPT expression is upregulated soon after head removal in previously non-expressing cells and in newly differentiating secretory cells. This activation of a head-specific gene precedes the morphologically obvious events of head regeneration. Pod-EPPT is one of the genes that are activated during manubrium (mouth) regeneration from experimentally combined subumbrellar plate endoderm and striated muscle of the medusa.

  18. Filamentation of plasma in the auroral region by an ion-ion instability: A process for the formation of bidimensional potential structures

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

    Mottez, F.; Chanteur, G.; Roux, A.

    1992-07-01

    A two-dimensional, explicit, electrostatic particle code is used to investigate the nonlinear behavior of electrostatic ion waves generated by an ion beam flowing through a thermal ion and electron background in a strongly magnetized plasma ({omega}{sub ce} {much gt} {omega}{sub pe} where {omega}{sub ce} and {omega}{sub pe} are the electron gyrofrequency and the plasma frequency). To follow the nonlinear evolution of these ions waves, a long-lasting simulation is run with a large simulation grid: 128 {times} 512{lambda}{sub d}. Beam ions are shown to generate oblique waves. The nonlinear beatings between these oblique waves produce purely transverse waves, which leads tomore » a strong modulation of the density and of the electric potential in a direction transverse to the magnetic field. The transverse scale of these essentially field-aligned filaments is L{sub {perpendicular}} = 10 {rho}{sub i} where {rho}{sub i} is the ion Larmor radius of beam ions. Within these filaments, relatively stable field-aligned density and potential structures develop. The typical size, along the magnetic field, of these structures is L{sub {parallel}} = 10 {lambda}{sub d}, the density is modulated by 30%, and the electric potential is as large as T{sub e} within these structures. Unlike the potential structures that develop in a two-component plasma with downgoing electrons, these structures move upward. These characteristics are in good agreement with the weak double layers recently detected by Viking.« less

  19. The effects of a pre-workout supplement containing caffeine, creatine, and amino acids during three weeks of high-intensity exercise on aerobic and anaerobic performance

    PubMed Central

    2010-01-01

    Background A randomized, single-blinded, placebo-controlled, parallel design study was used to examine the effects of a pre-workout supplement combined with three weeks of high-intensity interval training (HIIT) on aerobic and anaerobic running performance, training volume, and body composition. Methods Twenty-four moderately-trained recreational athletes (mean ± SD age = 21.1 ± 1.9 yrs; stature = 172.2 ± 8.7 cm; body mass = 66.2 ± 11.8 kg, VO2max = 3.21 ± 0.85 l·min-1, percent body fat = 19.0 ± 7.1%) were assigned to either the active supplement (GT, n = 13) or placebo (PL, n = 11) group. The active supplement (Game Time®, Corr-Jensen Laboratories Inc., Aurora, CO) was 18 g of powder, 40 kcals, and consisted of a proprietary blend including whey protein, cordyceps sinensis, creatine, citrulline, ginseng, and caffeine. The PL was also 18 g of powder, 40 kcals, and consisted of only maltodextrin, natural and artificial flavors and colors. Thirty minutes prior to all testing and training sessions, participants consumed their respective supplements mixed with 8-10 oz of water. Both groups participated in a three-week HIIT program three days per week, and testing was conducted before and after the training. Cardiovascular fitness (VO2max) was assessed using open circuit spirometry (Parvo-Medics TrueOne® 2400 Metabolic Measurement System, Sandy, UT) during graded exercise tests on a treadmill (Woodway, Pro Series, Waukesha, WI). Also, four high-speed runs to exhaustion were conducted at 110, 105, 100, and 90% of the treadmill velocity recorded during VO2max, and the distances achieved were plotted over the times-to-exhaustion. Linear regression was used to determine the slopes (critical velocity, CV) and y-intercepts (anaerobic running capacity, ARC) of these relationships to assess aerobic and anaerobic performances, respectively. Training volumes were tracked by summing the distances achieved during each training session for each subject. Percent body fat (%BF) and lean body mass (LBM) were assessed with air-displacement plethysmography (BOD POD®, Life Measurement, Inc., Concord, CA). Results Both GT and PL groups demonstrated a significant (p = 0.028) increase in VO2max from pre- to post-training resulting in a 10.3% and 2.9% improvement, respectively. CV increased (p = 0.036) for the GT group by 2.9%, while the PL group did not change (p = 0.256; 1.7% increase). ARC increased for the PL group by 22.9% and for the GT group by 10.6%. Training volume was 11.6% higher for the GT versus PL group (p = 0.041). %BF decreased from 19.3% to 16.1% for the GT group and decreased from 18.0% to 16.8% in the PL group (p = 0.178). LBM increased from 54.2 kg to 55.4 kg (p = 0.035) for the GT group and decreased from 52.9 kg to 52.4 kg in the PL group (p = 0.694). Conclusion These results demonstrated improvements in VO2max, CV, and LBM when GT is combined with HIIT. Three weeks of HIIT alone also augmented anaerobic running performance, VO2max and body composition. PMID:20156347

  20. [Susceptibility of Aedes aegypti to DDT, deltamethrin, and lambda-cyhalothrin in Colombia].

    PubMed

    Santacoloma Varón, Liliana; Chaves Córdoba, Bernardo; Brochero, Helena Luisa

    2010-01-01

    To assess the susceptibility status of 13 natural populations of Aedes aegypti (collected from sites in Colombia where dengue is a serious public health problem) to the pyrethroids, deltamethrin and lambda-cyhalothrin, and to the organochlorine, DDT, and to identify any biochemical mechanisms associated with resistance. Immature forms of the vector were collected from natural breeding spots at each site and then raised under controlled conditions. Using the F2 generation, bioassays were performed using the World Health Organization's 1981 methodology (impregnated paper) and United States Centers for Disease Control and Prevention's 1998 methodology (impregnated bottles). In populations where mortality rates were consistent with decreased susceptibility, levels of nonspecific esterases (NSE), mixed-function oxidases (MFO), and acetylcholinesterase (AChE) were measured using colorimetric tests. All of the mosquito populations that were tested showed resistance to the organochlorine DDT. In the case of the pyrethroids, widespread resistance to lambda-cyhalothrin was found, but not to deltamethrin. Assessing the biochemical resistance mechanisms showed that 7 of the 11 populations had elevated NSE, and one population, increased MFO. Physiological cross-resistance between DDT and lambda-cyhalothrin in the A. aegypti populations tested was dismissed. Physiological resistance to lambda-cyhalothrin appears to be associated with increased NSE. The differences in susceptibility levels and enzyme values among the populations were associated with genetic variations and chemicals in use locally.

  1. Phase shifting interferometer

    DOEpatents

    Sommargren, G.E.

    1999-08-03

    An interferometer is disclosed which has the capability of measuring optical elements and systems with an accuracy of {lambda}/1000 where {lambda} is the wavelength of visible light. Whereas current interferometers employ a reference surface, which inherently limits the accuracy of the measurement to about {lambda}/50, this interferometer uses an essentially perfect spherical reference wavefront generated by the fundamental process of diffraction. Whereas current interferometers illuminate the optic to be tested with an aberrated wavefront which also limits the accuracy of the measurement, this interferometer uses an essentially perfect spherical measurement wavefront generated by the fundamental process of diffraction. This interferometer is adjustable to give unity fringe visibility, which maximizes the signal-to-noise, and has the means to introduce a controlled prescribed relative phase shift between the reference wavefront and the wavefront from the optics under test, which permits analysis of the interference fringe pattern using standard phase extraction algorithms. 11 figs.

  2. Study of {Lambda}-{Lambda} oscillation in quantum coherent {Lambda}{Lambda} by using J/{psi}{yields}{Lambda}{Lambda} decay

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

    Kang Xianwei; Department of Physics, Henan Normal University, Xinxiang 453007; Li Haibo

    2010-03-01

    We discuss the possibility of searching for the {Lambda}-{Lambda} oscillations for coherent {Lambda}{Lambda} production in the J/{psi}{yields}{Lambda}{Lambda} decay process. The sensitivity of measurement of {Lambda}-{Lambda} oscillation in the external field at BES-III experiment is considered. These considerations indicate an alternative way to probe the {Delta}B=2 amplitude in addition to neutron oscillation experiments. Both coherent and time-dependent information can be used to extract the {Lambda}-{Lambda} oscillation parameter. With one year's luminosity at BES-III, we can set an upper limit of {delta}m{sub {Lambda}{Lambda}<}10{sup -15} MeV at 90% confidence level, corresponding to about 10{sup -6} s of {Lambda}-{Lambda} oscillation time.

  3. Comparative Analysis of the Lambda-Interferons IL-28A and IL-29 regarding Their Transcriptome and Their Antiviral Properties against Hepatitis C Virus

    PubMed Central

    Diegelmann, Julia; Beigel, Florian; Zitzmann, Kathrin; Kaul, Artur; Göke, Burkhard; Auernhammer, Christoph J.; Bartenschlager, Ralf; Diepolder, Helmut M.; Brand, Stephan

    2010-01-01

    Background Specific differences in signaling and antiviral properties between the different Lambda-interferons, a novel group of interferons composed of IL-28A, IL-28B and IL-29, are currently unknown. This is the first study comparatively investigating the transcriptome and the antiviral properties of the Lambda-interferons IL-28A and IL-29. Methodology/Principal Findings Expression studies were performed by microarray analysis, quantitative PCR (qPCR), reporter gene assays and immunoluminometric assays. Signaling was analyzed by Western blot. HCV replication was measured in Huh-7 cells expressing subgenomic HCV replicon. All hepatic cell lines investigated as well as primary hepatocytes expressed both IFN-λ receptor subunits IL-10R2 and IFN-λR1. Both, IL-28A and IL-29 activated STAT1 signaling. As revealed by microarray analysis, similar genes were induced by both cytokines in Huh-7 cells (IL-28A: 117 genes; IL-29: 111 genes), many of them playing a role in antiviral immunity. However, only IL-28A was able to significantly down-regulate gene expression (n = 272 down-regulated genes). Both cytokines significantly decreased HCV replication in Huh-7 cells. In comparison to liver biopsies of patients with non-viral liver disease, liver biopsies of patients with HCV showed significantly increased mRNA expression of IL-28A and IL-29. Moreover, IL-28A serum protein levels were elevated in HCV patients. In a murine model of viral hepatitis, IL-28 expression was significantly increased. Conclusions/Significance IL-28A and IL-29 are up-regulated in HCV patients and are similarly effective in inducing antiviral genes and inhibiting HCV replication. In contrast to IL-29, IL-28A is a potent gene repressor. Both IFN-λs may have therapeutic potential in the treatment of chronic HCV. PMID:21170333

  4. Cloning of a cDNA encoding bovine mitochondrial NADP(+)-specific isocitrate dehydrogenase and structural comparison with its isoenzymes from different species.

    PubMed Central

    Huh, T L; Ryu, J H; Huh, J W; Sung, H C; Oh, I U; Song, B J; Veech, R L

    1993-01-01

    Mitochondrial NADP(+)-specific isocitrate dehydrogenase (IDP) was co-purified with the pyruvate dehydrogenase complex from bovine kidney mitochondria. The determination of its N-terminal 16-amino-acid sequence revealed that it is highly similar to the IDP from yeast. A cDNA clone (1.8 kb long) encoding this protein was isolated from a bovine kidney lambda gt11 cDNA library using a synthetic oligodeoxynucleotide. The deduced protein sequence of this cDNA clone rendered a precursor protein of 452 amino-acid residues (50,830 Da) and a mature protein of 413 amino-acid residues (46,519 Da). It is 100% identical to the internal tryptic peptide sequences of the autologous form from pig heart and 62% similar to that from yeast. However, it shares little similarity with the mitochondrial NAD(+)-specific isoenzyme from yeast. Structural analyses of the deduced proteins of IDP isoenzymes from different species indicated that similarity exists in certain regions, which may represent the common domains for the active sites or coenzyme-binding sites. In Northern-blot analysis, one species of mRNA (about 2.2 kb for both bovine and human) was hybridized with a 32P-labelled cDNA probe. Southern-blot analysis of genomic DNAs verified simple patterns of hybridization with this cDNA. These results strongly indicate that the mitochondrial IDP may be derived from a single gene family which does not appear to be closely related to that of the NAD(+)-specific isoenzyme. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:8318002

  5. Electrical and thermoelectric transport properties of two-dimensional fermionic systems with k-cubic spin-orbit coupling.

    PubMed

    Mawrie, Alestin; Verma, Sonu; Ghosh, Tarun Kanti

    2017-09-01

    We investigate effect of <i>k</i>-cubic spin-orbit interaction on electrical and thermoelectric transport properties of two-dimensional fermionic systems. We obtain exact analytical expressions of the inverse relaxation time (IRT) and the Drude conductivity for long-range Coulomb and short-range delta scattering potentials. The IRT reveals that the scattering is completely suppressed along the three directions θ = (2n+1)π/3 with n=1,2,3. We also obtain analytical results of the thermopower and thermal conductivity at low temperature. The thermoelectric transport coefficients obey the Wiedemann-Franz law, even in the presence of <i>k</i>-cubic Rashba spin-orbit interaction (RSOI) at low temperature. In the presence of quantizing magnetic field, the signature of the RSOI is revealed through the appearance of the beating pattern in the Shubnikov-de Haas (SdH) oscillations of thermopower and thermal conductivity in low magnetic field regime. The empirical formulae for the SdH oscillation frequencies accurately describe the locations of the beating nodes. The beating pattern in magnetothermoelectric measurement can be used to extract the spin-orbit coupling constant. © 2017 IOP Publishing Ltd.

  6. The development and validity of the Salford Gait Tool: an observation-based clinical gait assessment tool.

    PubMed

    Toro, Brigitte; Nester, Christopher J; Farren, Pauline C

    2007-03-01

    To develop the construct, content, and criterion validity of the Salford Gait Tool (SF-GT) and to evaluate agreement between gait observations using the SF-GT and kinematic gait data. Tool development and comparative evaluation. University in the United Kingdom. For designing construct and content validity, convenience samples of 10 children with hemiplegic, diplegic, and quadriplegic cerebral palsy (CP) and 152 physical therapy students and 4 physical therapists were recruited. For developing criterion validity, kinematic gait data of 13 gait clusters containing 56 children with hemiplegic, diplegic, and quadriplegic CP and 11 neurologically intact children was used. For clinical evaluation, a convenience sample of 23 pediatric physical therapists participated. We developed a sagittal plane observational gait assessment tool through a series of design, test, and redesign iterations. The tool's grading system was calibrated using kinematic gait data of 13 gait clusters and was evaluated by comparing the agreement of gait observations using the SF-GT with kinematic gait data. Criterion standard kinematic gait data. There was 58% mean agreement based on grading categories and 80% mean agreement based on degree estimations evaluated with the least significant difference method. The new SF-GT has good concurrent criterion validity.

  7. Spontaneous mutations of the UDP-glucose:flavonoid 3-O-glucosyltransferase gene confers pale- and dull-colored flowers in the Japanese and common morning glories.

    PubMed

    Morita, Yasumasa; Ishiguro, Kanako; Tanaka, Yoshikazu; Iida, Shigeru; Hoshino, Atsushi

    2015-09-01

    UDP-glucose:flavonoid 3- O -glucosyltransferase is essential for maintaining proper production quantity, acylation, and glucosylation of anthocyanin, and defects cause pale and dull flower pigmentation in morning glories. The Japanese (Ipomoea nil) and the common (I. purpurea) morning glory display bright blue and dark purple flowers, respectively. These flowers contain acylated and glucosylated anthocyanin pigments, and a number of flower color mutants have been isolated in I. nil. Of these, the duskish mutants of I. nil produce pale- and dull-colored flowers. We found that the Duskish gene encodes UDP-glucose:flavonoid 3-O-glucosyltransferase (3GT). The duskish-1 mutation is a frameshift mutation caused by a 4-bp insertion, and duskish-2 is an insertion of a DNA transposon, Tpn10, at 1.3 kb upstream of the 3GT start codon. In the duskish-2 mutant, excision of Tpn10 is responsible for restoration of the expression of the 3GT gene. The recombinant 3GT protein displays expected 3GT enzymatic activities to catalyze 3-O-glucosylation of anthocyanidins in vitro. Anthocyanin analysis of a duskish-2 mutant and its germinal revertant showing pale and normal pigmented flowers, respectively, revealed that the mutation caused around 80 % reduction of anthocyanin accumulation. We further characterized two I. purpurea mutants showing pale brownish-red flowers, and found that they carry the same frameshift mutation in the 3GT gene. Most of the flower anthocyanins in the mutants were previously found to be anthocyanidin 3-O-glucosides lacking several caffeic acid and glucose moieties that are attached to the anthocyanins in the wild-type plants. These results indicated that 3GT is essential not only for production, but also for proper acylation and glucosylation, of anthocyanin in the morning glories.

  8. Antiviral Activity and Resistance Analysis of NS3/4A Protease Inhibitor Grazoprevir and NS5A Inhibitor Elbasvir in Hepatitis C Virus GT4 Replicons.

    PubMed

    Asante-Appiah, Ernest; Curry, Stephanie; McMonagle, Patricia; Ingravallo, Paul; Chase, Robert; Nickle, David; Qiu, Ping; Howe, Anita; Lahser, Frederick C

    2017-07-01

    Although genotype 4 (GT4)-infected patients represent a minor overall percentage of the global hepatitis C virus (HCV)-infected population, the high prevalence of the genotype in specific geographic regions coupled with substantial sequence diversity makes it an important genotype to study for antiviral drug discovery and development. We evaluated two direct-acting antiviral agents-grazoprevir, an HCV NS3/4A protease inhibitor, and elbasvir, an HCV NS5A inhibitor-in GT4 replicons prior to clinical studies in this genotype. Following a bioinformatics analysis of available GT4 sequences, a set of replicons bearing representative GT4 clinical isolates was generated. For grazoprevir, the 50% effective concentration (EC 50 ) against the replicon bearing the reference GT4a (ED43) NS3 protease and NS4A was 0.7 nM. The median EC 50 for grazoprevir against chimeric replicons encoding NS3/4A sequences from GT4 clinical isolates was 0.2 nM (range, 0.11 to 0.33 nM; n = 5). The difficulty in establishing replicons bearing NS3/4A resistance-associated substitutions was substantially overcome with the identification of a G162R adaptive substitution in NS3. Single NS3 substitutions D168A/V identified from de novo resistance selection studies reduced grazoprevir antiviral activity by 137- and 47-fold, respectively, in the background of the G162R replicon. For elbasvir, the EC 50 against the replicon bearing the reference full-length GT4a (ED43) NS5A gene was 0.0002 nM. The median EC 50 for elbasvir against chimeric replicons bearing clinical isolates from GT4 was 0.0007 nM (range, 0.0002 to 34 nM; n = 14). De novo resistance selection studies in GT4 demonstrated a high propensity to suppress the emergence of amino acid substitutions that confer high-potency reductions to elbasvir. Phenotypic characterization of the NS5A amino acid substitutions identified (L30F, L30S, M31V, and Y93H) indicated that they conferred 15-, 4-, 2.5-, and 7.5-fold potency losses, respectively, to elbasvir. The activity profiles of grazoprevir and elbasvir supported the testing of the direct-acting antivirals in clinical studies. Copyright © 2017 American Society for Microbiology.

  9. Detection of silicate emission features in the 8- to 13-micron spectra of main belt asteroids

    NASA Technical Reports Server (NTRS)

    Feierberg, M. A.; Witteborn, F. C.; Lebofsky, L. A.

    1983-01-01

    A presentation is given of 8.0-13.0 micron spectra (Delta lambda/lambda = 0.02-0.03) for six main belt asteroids, which range from 58 to 220 km in diameter and sample the five principal taxonomic classes (C, S, M, R and E). Narrow, well-defined silicate emission features are present on two of the asteroids, the C-type 19 Fortuna and the M-type 21 Lutetia. No comparable emission features are observed on the S-types 11 Parthenope and 14 Irene, the R-type 349 Dembowska or the E-type 64 Angelina.

  10. Stress perception and (GT)n repeat polymorphism in haem oxygenase 1 promoter are both risk factors in development of eating disorders.

    PubMed

    Slachtová, L; Kaminská, D; Chvál, M; Králík, L; Martásek, P; Papežová, H

    2013-01-01

    Haem oxygenase 1 (HO-1) plays a pivotal role in metabolic stress protecting cells in dependence on reactive oxygen species. This study investigated a potential gene environment interaction between the (GT)n repeat HO1 polymorphism and the stress perception in patients with eating disorder and in controls. Stress perception and (GT)n polymorphism were measured in 127 patients with eating disorders and in 78 healthy controls using Stress and Coping Inventory and genotyping. Based on the inventory, overall, specific and weighted stress scores were defined. Clinical stress score was generated according to the patient's history and interviews. According to our hypothesis, 1) all stress scores describing subjective stress perception were significantly higher in patients compared to controls (P ≤ 0.001; P ≤ 0.002; P ≤ 0.001), 2) the L/L genotype of GT promoter repeats (L < 25 GT repeats, S < 25 GT repeats) in the patients was associated with higher overall (P ≤ 0.001), specific (P ≤ 0.010) and weighted stress score (P ≤ 0.005) compared to the L/S variant, and 3) Pearson's correlation of clinical versus objective stress scores showed not very tight relationship (0.198; 0.287; 0.224, respectively). We assume potential risk of the L allele of HO1 promoter polymorphism for the stress response and contribution of the subjective stress perception together with the L/L genotype to the development of eating disorder. Decreased HO1 expression in the presence of L/L genotype plus more intensive stress perception in the patients can lead to secondary stress, with increasing severity of the symptoms and aggravation of the disease.

  11. Hymenobacter seoulensis sp. nov., isolated from river water.

    PubMed

    Lee, Jae-Jin; Lee, Yeon-Hee; Park, Su-Jin; Lee, Seung-Yeol; Park, Sangkyu; Kim, Myung Kyum; Ten, Leonid N; Jung, Hee-Young

    2017-04-01

    A Gram-stain-negative, aerobic, rod-shaped, non-motile and pink-pigmented bacterial strain, designated 16F7GT, was isolated from river water. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain 16F7GT belongs to the genus Hymenobacter. The 16S rRNA gene sequence similarity to members of the genus Hymenobacter ranged from 90.5 to 97.4 %, and the most closely related strains were Hymenobacter rigui WPCB131T (97.4 %) and Hymenobacter xinjiangensis X2-1gT (97.3 %). Strain 16F7GT had <70 % DNA-DNA relatedness with H. rigui (32.8±7.8 %) and H. xinjiangensis (30.2±6.2 %), indicating that it represents a novel genospecies. Cells were catalase- and oxidase-positive. The genomic DNA G+C content was 56.6 mol%. The major fatty acids were summed feature 4 (C17 : 1iso I/C17 : 1 anteiso B; 19.8 %), summed feature 3 (C16 : 1ω7c/C16 : 1ω6c; 18.4 %), C15 : 0 iso (17.0 %), C16 : 1ω5c (11.8 %) and C15 : 0 anteiso (9.8 %). The major polar lipid was phosphatidylethanolamine and the predominant respiratory quinone was menaquinone 7 (MK-7). Based on the phylogenetic, phenotypic, genotypic and chemotaxonomic analyses, it is concluded that strain 16F7GT represents a novel species within the genus Hymenobacter, for which the name Hymenobacter seoulensis sp. nov. is proposed. The type strain is 16F7GT (=KCTC 52197T=JCM 31655T).

  12. An Empirically Calibrated Model of Cell Fate Decision Following Viral Infection

    NASA Astrophysics Data System (ADS)

    Coleman, Seth; Igoshin, Oleg; Golding, Ido

    The life cycle of the virus (phage) lambda is an established paradigm for the way genetic networks drive cell fate decisions. But despite decades of interrogation, we are still unable to theoretically predict whether the infection of a given cell will result in cell death or viral dormancy. The poor predictive power of current models reflects the absence of quantitative experimental data describing the regulatory interactions between different lambda genes. To address this gap, we are constructing a theoretical model that captures the known interactions in the lambda network. Model assumptions and parameters are calibrated using new single-cell data from our lab, describing the activity of lambda genes at single-molecule resolution. We began with a mean-field model, aimed at exploring the population averaged gene-expression trajectories under different initial conditions. Next, we will develop a stochastic formulation, to capture the differences between individual cells within the population. The eventual goal is to identify how the post-infection decision is driven by the interplay between network topology, initial conditions, and stochastic effects. The insights gained here will inform our understanding of cell fate choices in more complex cellular systems.

  13. Electron excitation cross sections for the 2s(2)2p(3)4S(O) -- 2s(2)2p(3)2D(O) (forbidden) and 4S(O) -- 2s2p(4) 4P (resonance) transitions in O II

    NASA Technical Reports Server (NTRS)

    Zuo, M.; Smith, Steven J.; Chutjian, A.; Williams, I. D.; Tayal, S. S.; Mclaughlin, Brendan M.

    1995-01-01

    Experimental and theoretical excitation cross sections are reported for the first forbidden transition 4S(O) -- 2S(2)2p(3) 2D(O) (lambda-lambda 3726, 3729) and the first allowed (resonance) transition 4S(O) -- 2s2p(4) 4P(lambda-833) in O II. Use is made of electron energy loss and merged-beams methods. The electron energy range covered is 3.33 (threshold) to 15 eV for the S -- D transition, and 14.9 (threshold) to 40 eV for the S -- P transition. Care was taken to assess and minimize the metastable fraction of the O II beam. An electron mirror was designed and tested to reflect inelastically backscattered electrons into the forward direction to account for the full range of polar scattering angles. Comparisons are made between present experiments and 11-state R-matrix calculations. Calculations are also presented for the 4S(O) -- 2s(2)2p(3)2P(O) (lambda-2470) transition.

  14. Enhanced peculiar velocities in brane-induced gravity

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

    Wyman, Mark; Khoury, Justin

    The mounting evidence for anomalously large peculiar velocities in our Universe presents a challenge for the {Lambda}CDM paradigm. The recent estimates of the large-scale bulk flow by Watkins et al. are inconsistent at the nearly 3{sigma} level with {Lambda}CDM predictions. Meanwhile, Lee and Komatsu have recently estimated that the occurrence of high-velocity merging systems such as the bullet cluster (1E0657-57) is unlikely at a 6.5-5.8{sigma} level, with an estimated probability between 3.3x10{sup -11} and 3.6x10{sup -9} in {Lambda}CDM cosmology. We show that these anomalies are alleviated in a broad class of infrared-modifed gravity theories, called brane-induced gravity, in which gravitymore » becomes higher-dimensional at ultralarge distances. These theories include additional scalar forces that enhance gravitational attraction and therefore speed up structure formation at late times and on sufficiently large scales. The peculiar velocities are enhanced by 24-34% compared to standard gravity, with the maximal enhancement nearly consistent at the 2{sigma} level with bulk flow observations. The occurrence of the bullet cluster in these theories is {approx_equal}10{sup 4} times more probable than in {Lambda}CDM cosmology.« less

  15. 76 FR 34197 - Anchorage; Change to Cottonwood Island Anchorage, Columbia River, Oregon and Washington

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-13

    .... * * * * * Dated: May 11, 2011. G.T. Blore, Rear Admiral, U.S. Coast Guard Commander, Thirteenth Coast Guard.... Voluntary consensus standards are technical standards (e.g., specifications of materials, performance...

  16. 75 FR 16002 - Drawbridge Operation Regulation; Chehalis River, Aberdeen, WA, Schedule Change

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-31

    ...: March 11, 2010. G.T. Blore, Rear Admiral, U.S. Coast Guard, Commander, Thirteenth Coast Guard District... standards (e.g., specifications of materials, performance, design, or operation; test methods; sampling...

  17. Mutations of the phage lambda nutL region that prevent the action of Nun, a site-specific transcription termination factor.

    PubMed Central

    Baron, J; Weisberg, R A

    1992-01-01

    Phage HK022 encodes a protein, Nun, that promotes transcription termination within the pL and pR operons of its relative, phage lambda. The lambda sequences required for termination had previously been shown to overlap the nut sites, which are essential for transcription antitermination during normal lambda growth. To further specify the Nun target and to determine its relation to the nut sites, we constructed deletion and base substitution mutations of the lambda nutL region and measured Nun-dependent reduction of the expression of a downstream reporter gene. The shortest construct that retained full Nun responsiveness was a 42-bp segment that included both boxA and boxB, sequences that have been implicated in lambda antitermination. Deletion of boxA reduced Nun termination, and deletion of both sequences eliminated Nun termination. Base substitutions in boxA and the proximal portion of boxB impaired Nun termination, while base substitutions between boxA and boxB, in the distal portion of boxB, and immediately downstream from boxB had no appreciable effect. The termination defect of all of the base substitution mutations was relieved by increasing the level of Nun protein; in contrast, the deletions and a multiple-base substitution did not regain full Nun responsiveness at elevated Nun concentrations. We also asked if these mutant nut regions retained their ability to interact with N, the lambda-encoded antitermination protein. A qualitative assay showed that mutations within boxA or boxB reduced interaction, while mutations outside boxA and boxB did not. These data show that (i) the recognition sites for N and Nun overlap to a very considerable extent but are probably not identical and (ii) a high concentration of Nun promotes its interaction with mutant nut sites, a behavior also reported to be characteristic of N. PMID:1532174

  18. Docking - Gemini-Titan (GT)-11 - Outer Space

    NASA Image and Video Library

    1966-09-14

    S66-54555 (14 Sept. 1966) --- The Gemini-11 spacecraft is docked to the Agena Target Vehicle in this photograph taken by astronaut Richard F. Gordon Jr., pilot, as he stood in the open hatch of the Gemini-11 spacecraft during his extravehicular activity (EVA). Note Agena's L-band antenna. Taken during Gemini-11's 29th revolution of Earth, using a modified 70mm Hasselblad camera, with Eastman Kodak, Ektachrome, MS (S.O. 368) color film. Photo credit: NASA

  19. Bruton's tyrosine kinase and SLP-65 regulate pre-B cell differentiation and the induction of Ig light chain gene rearrangement.

    PubMed

    Kersseboom, Rogier; Ta, Van B T; Zijlstra, A J Esther; Middendorp, Sabine; Jumaa, Hassan; van Loo, Pieter Fokko; Hendriks, Rudolf W

    2006-04-15

    Bruton's tyrosine kinase (Btk) and the adapter protein SLP-65 (Src homology 2 domain-containing leukocyte-specific phosphoprotein of 65 kDa) transmit precursor BCR (pre-BCR) signals that are essential for efficient developmental progression of large cycling into small resting pre-B cells. We show that Btk- and SLP-65-deficient pre-B cells have a specific defect in Ig lambda L chain germline transcription. In Btk/SLP-65 double-deficient pre-B cells, both kappa and lambda germline transcripts are severely reduced. Although these observations point to an important role for Btk and SLP-65 in the initiation of L chain gene rearrangement, the possibility remained that these signaling molecules are only required for termination of pre-B cell proliferation or for pre-B cell survival, whereby differentiation and L chain rearrangement is subsequently initiated in a Btk/SLP-65-independent fashion. Because transgenic expression of the antiapoptotic protein Bcl-2 did not rescue the developmental arrest of Btk/SLP-65 double-deficient pre-B cells, we conclude that defective L chain opening in Btk/SLP-65-deficient small resting pre-B cells is not due to their reduced survival. Next, we analyzed transgenic mice expressing the constitutively active Btk mutant E41K. The expression of E41K-Btk in Ig H chain-negative pro-B cells induced 1) surface marker changes that signify cellular differentiation, including down-regulation of surrogate L chain and up-regulation of CD2, CD25, and MHC class II; and 2) premature rearrangement and expression of kappa and lambda light chains. These findings demonstrate that Btk and SLP-65 transmit signals that induce cellular maturation and Ig L chain rearrangement independently of their role in termination of pre-B cell expansion.

  20. Stepwise morphological evolution of the active Yellow River (Huanghe) delta lobe (1976-2013): Dominant roles of riverine discharge and sediment grain size

    NASA Astrophysics Data System (ADS)

    Wu, Xiao; Bi, Naishuang; Xu, Jingping; Nittrouer, Jeffrey A.; Yang, Zuosheng; Saito, Yoshiki; Wang, Houjie

    2017-09-01

    The presently active Yellow River (Huanghe) delta lobe has been formed since 1976 when the river was artificially diverted. The process and driving forces of morphological evolution of the present delta lobe still remain unclear. Here we examined the stepwise morphological evolution of the active Yellow River delta lobe including both the subaerial and the subaqueous components, and illustrated the critical roles of riverine discharge and sediment grain size in dominating the deltaic evolution. The critical sediment loads for maintaining the delta stability were also calculated from water discharge and sediment load measured at station Lijin, the last gauging station approximately 100 km upstream from the river mouth. The results indicated that the development of active delta lobe including both subaerial and subaqueous components has experienced four sequential stages. During the first stage (1976-1981) after the channel migration, the unchannelized river flow enhanced deposition within the channel and floodplain between Lijin station and the river mouth. Therefore, the critical sediment supply calculated by the river inputs obtained from station Lijin was the highest. However, the actual sediment load at this stage (0.84 Gt/yr) was more than twice of the critical sediment load ( 0.35 Gt/yr) for sustaining the active subaerial area, which favored a rapid seaward progradation of the Yellow River subaerial delta. During the second stage (1981-1996), the engineering-facilitated channelized river flow and the increase in median grain size of suspended sediment delivered to the sea resulted in the critical sediment load for keeping the delta stability deceasing to 0.29 Gt/yr. The active delta lobe still gradually prograded seaward at an accretion rate of 11.9 km2/yr at this stage as the annual sediment load at Lijin station was 0.55 Gt/yr. From 1996 to 2002, the critical sediment load further decreased to 0.15 Gt/yr with the sediment grain size increased to 22.5 μm; however, the delta suffered net erosion because of the insufficient sediment supply (0.11 Gt/yr). In the most recent stage (2002 - 2013), the intensive scouring of the lower river channel induced by the dam regulation provided relatively coarser sediment, which effectively reduced the critical sediment load to 0.06 Gt/yr, much lower than the corresponding sediment load at Lijin station ( 0.16 Gt/yr). Consequently, the subaerial Yellow River delta transitioned to a slight accretion phase. Overall, the evolution of the active Yellow River delta is highly correlated to riverine water and sediment discharge. The sediment supply for keeping the subaerial delta stability is inconstant and varying with the river channel morphology and sediment grain size. We conclude that the human-impacted riverine sediment discharge and grain-size composition play dominant roles in the stepwise morphological evolution of the active delta lobe.

  1. Magnetic and electronic properties of the Cu-substituted Weyl semimetal candidate ZrCo2Sn.

    PubMed

    Kushwaha, S K; Wang, Zhijun; Kong, Tai; Cava, Robert

    2018-01-04

    We report that the partial substitution of Cu for Co has a significant impact on the magnetic properties of the Heusler-phase Weyl fermion candidate ZrCo<sub>2</sub>Sn. Polycrystalline samples of ZrCo<sub>2-<i>x</i></sub>Cu<sub><i>x</i></sub>Sn (<i>x</i> = 0.0 to 1.0) exhibited a linearly decreasing ferromagnetic transition temperature and similarly decreasing saturated magnetic moment on increasing Cu substitution x. Materials with Cu contents near <i>x</i> = 1 and several other quaternary materials synthesized at the same <i>x</i> (ZrCo<i>T</i>'Sn (<i>T</i>' = Rh, Pd, Ni)) display what appears to be non-ferromagnetic magnetization behavior with spin glass characteristics. Electronic structure calculations suggest that the half-metallic nature of unsubstituted ZrCo<sub>2</sub>Sn is disrupted significantly by the Cu substitutions, leading to the breakdown of the magnetization vs. electron count guidelines usually followed by Heusler phases, and a more typical metallic non-spin-polarized electronic structure at high <i>x</i>. © 2018 IOP Publishing Ltd.

  2. Demonstration of Broadband Contrast at 1.2 Lambda/D for the EXCEDE Phase-Induced Amplitude Apodization Coronagraph

    NASA Technical Reports Server (NTRS)

    Sirbu, Dan; Thomas, Sandrine J.; Belikov, Ruslan; Lozi, Julien; Bendek, Eduardo; Pluzhnik, Eugene; Lynch, Dana H.; Hix, Troy; Zell, Peter; Schneider, Glenn; hide

    2015-01-01

    The proposed coronagraph instrument on the EXCEDE (EXoplanetary Circumstellar Environments and Disk Explorer) mission study uses a Phase-Induced Amplitude Apodization (PIAA) coronagraph architecture to enable high-contrast imaging of circumstellar debris disks and giant planets at angular separations as close in as the habitable zone of nearby host stars. We report on the experimental results obtained in the vacuum chamber at the Lockheed Martin Advanced Technology Center in 10 percent broadband light centered about 650 nanometers, with a median contrast of 1 x 10 (sup -5) between 1.2 and 2.0 lambda /D simultaneously with 3 x 10 (sup -7) contrast between 2 and 11 =D between 2 and 11 lambda/D for a single-sided dark hole using a deformable mirror (DM) upstream of the PIAA coronagraph. The results are stable and repeatable as demonstrated by three measurements runs with DM settings set from scratch and maintained on the best 90 percent out of the 1000 collected frames. We compare the reduced experimental data with simulation results from modeling observed experimental limits; performance is consistent with uncorrected low-order modes not estimated by the Low Order Wavefront Sensor (LOWFS). Modeled sensitivity to bandwidth and residual tip/tilt modes is well-matched to the experiment.

  3. Magnetization, resistivity, specific heat and ab initio calculations of Gd5Sb3.

    PubMed

    Samatham, S Shanmukharao; Patel, Akhilesh Kumar; Lukoyanov, Alexey V; Suresh, K G

    2018-06-07

    We report on the combined results of structural, magnetic, transport and calorimetric properties of Mn<sub>5</sub>Si<sub>3</sub>-type hexagonal Gd<sub>5</sub>Sb<sub>3</sub>, together with <i>ab-initio</i> calculations. It exhibits a ferromagnetic (FM)-like transition at 265 K, antiferromagnetic (AFM) Néel transition at 95.5 K followed by a spin-orientation transition at 62 K. The system is found to be in AFM state down to 2 K in a field of 70 kOe. The FM-AFM phase coexistence is not noticeable despite large positive Curie-Weiss temperature (θ<sub>CW</sub> = 223.5 ± 0.2 K). Instead, low-temperature AFM and high-temperature FM-like phases are separated in large temperatures. Temperature-magnetic field (<i>H</i>-<i>T</i>) phase diagram reveals field-driven complex magnetic phases. Within the AFM phase, the system is observed to undergo field-driven spin-orientation transitions. Field-induced tricritical and quantum critical points appear to be absent due to strong AFM nature and by the intervention of FM-like state between paramagnetic and AFM states, respectively. The metallic behavior of the compound is inferred from resistivity along with large Sommerfeld parameter. However, no sign of strong electron-correlations is reasoned from the Kadowaki-Wood's ratio <i>A</i>/γ<sup>2</sup> ∼ 1.9×10<sup>-6</sup> μΩ.cm.(mol.K)<sup>2</sup>(mJ)<sup>-2</sup>, despite heavy γ. Essentially, <i>ab initio</i> calculations accounting for electronic correlations confirm AFM nature of low-temperature magnetic state in Gd<sub>5</sub>Sb<sub>3</sub> and attainable FM ordering in agreement with experimental data. © 2018 IOP Publishing Ltd.

  4. Dual color microscopic imagery of cells expressing the green fluorescent protein and a red-shifted variant.

    PubMed

    Yang, T T; Kain, S R; Kitts, P; Kondepudi, A; Yang, M M; Youvan, D C

    1996-01-01

    The green fluorescent protein (GFP) from the jellyfish, Aequorea victoria, has become a versatile reporter for monitoring gene expression and protein localization in a variety of cells and organisms. GFP emits bright green light (lambda max = 510 nm) when excited with ultraviolet (UV) or blue light (lambda max = 395 nm, minor peak at 470 nm). The chromophore in GFP is intrinsic to the primary structure of the protein, and fluorescence from GFP does not require additional gene products, substrates or other factors. GFP fluorescence is stable, species-independent and can be monitored noninvasively using the techniques of fluorescence microscopy and flow cytometry [Chalfie et al., Science 263 (1994) 802-805; Stearns, Curr. Biol. 5 (1995) 262-264]. The protein appears to undergo an autocatalytic reaction to create the fluorophore [Heim et al., Proc. Natl. Acad. Sci. USA 91 (1994) 12501-12504] in a process involving cyclization of a Tyr66 aa residue. Recently [Delagrave et al., Bio/Technology 13 (1995) 151-154], a combinatorial mutagenic strategy was targeted at aa 64 through 69, which spans the chromophore of A. victoria GFP, yielding a number of different mutants with red-shifted fluorescence excitation spectra. One of these, RSGFP4, retains the characteristic green emission spectra (lambda max = 505 nm), but has a single excitation peak (lambda max = 490 nm). The fluorescence properties of RSGFP4 are similar to those of another naturally occurring GFP from the sea pansy, Renilla reniformis [Ward and Cormier, Photobiochem. Photobiol. 27 (1978) 389-396]. In the present study, we demonstrate by fluorescence microscopy that selective excitation of A. victoria GFP and RSGFP4 allows for spectral separation of each fluorescent signal, and provides the means to image these signals independently in a mixed population of bacteria or mammalian cells.

  5. Metadata Analysis of Phanerochaete chrysosporium Gene Expression Data Identified Common CAZymes Encoding Gene Expression Profiles Involved in Cellulose and Hemicellulose Degradation.

    PubMed

    Kameshwar, Ayyappa Kumar Sista; Qin, Wensheng

    2017-01-01

    In literature, extensive studies have been conducted on popular wood degrading white rot fungus, Phanerochaete chrysosporium about its lignin degrading mechanisms compared to the cellulose and hemicellulose degrading abilities. This study delineates cellulose and hemicellulose degrading mechanisms through large scale metadata analysis of P. chrysosporium gene expression data (retrieved from NCBI GEO) to understand the common expression patterns of differentially expressed genes when cultured on different growth substrates. Genes encoding glycoside hydrolase classes commonly expressed during breakdown of cellulose such as GH-5,6,7,9,44,45,48 and hemicellulose are GH-2,8,10,11,26,30,43,47 were found to be highly expressed among varied growth conditions including simple customized and complex natural plant biomass growth mediums. Genes encoding carbohydrate esterase class enzymes CE (1,4,8,9,15,16) polysaccharide lyase class enzymes PL-8 and PL-14, and glycosyl transferases classes GT (1,2,4,8,15,20,35,39,48) were differentially expressed in natural plant biomass growth mediums. Based on these results, P. chrysosporium, on natural plant biomass substrates was found to express lignin and hemicellulose degrading enzymes more than cellulolytic enzymes except GH-61 (LPMO) class enzymes, in early stages. It was observed that the fate of P. chrysosporium transcriptome is significantly affected by the wood substrate provided. We believe, the gene expression findings in this study plays crucial role in developing genetically efficient microbe with effective cellulose and hemicellulose degradation abilities.

  6. Resistance to lambda-cyhalothrin in Spanish field populations of Ceratitis capitata and metabolic resistance mediated by P450 in a resistant strain.

    PubMed

    Arouri, Rabeh; Le Goff, Gaelle; Hemden, Hiethem; Navarro-Llopis, Vicente; M'saad, Mariem; Castañera, Pedro; Feyereisen, René; Hernández-Crespo, Pedro; Ortego, Félix

    2015-09-01

    The withdrawal of malathion in the European Union in 2009 resulted in a large increase in lambda-cyhalothrin applications for the control of the Mediterranean fruit fly, Ceratitis capitata, in Spanish citrus crops. Spanish field populations of C. capitata have developed resistance to lambda-cyhalothrin (6-14-fold), achieving LC50 values (129-287 ppm) higher than the recommended concentration for field treatments (125 ppm). These results contrast with the high susceptibility to lambda-cyhalothrin found in three Tunisian field populations. We have studied the mechanism of resistance in the laboratory-selected resistant strain W-1Kλ (205-fold resistance). Bioassays with synergists showed that resistance was almost completely suppressed by the P450 inhibitor PBO. The study of the expression of 53 P450 genes belonging to the CYP4, CYP6, CYP9 and CYP12 families in C. capitata revealed that CYP6A51 was overexpressed (13-18-fold) in the resistant strain. The W-1Kλ strain also showed high levels of cross-resistance to etofenprox (240-fold) and deltamethrin (150-fold). Field-evolved resistance to lambda-cyhalothrin has been found in C. capitata. Metabolic resistance mediated by P450 appears to be the main resistance mechanism in the resistant strain W-1Kλ. The levels of cross-resistance found may compromise the effectiveness of other pyrethroids for the control of this species. © 2014 Society of Chemical Industry. © 2014 Society of Chemical Industry.

  7. The Gediz River fluvial archive: A benchmark for Quaternary research in Western Anatolia

    NASA Astrophysics Data System (ADS)

    Maddy, D.; Veldkamp, A.; Demir, T.; van Gorp, W.; Wijbrans, J. R.; van Hinsbergen, D. J. J.; Dekkers, M. J.; Schreve, D.; Schoorl, J. M.; Scaife, R.; Stemerdink, C.; van der Schriek, T.; Bridgland, D. R.; Aytaç, A. S.

    2017-06-01

    The Gediz River, one of the principal rivers of Western Anatolia, has an extensive Pleistocene fluvial archive that potentially offers a unique window into fluvial system behaviour on the western margins of Asia during the Quaternary. In this paper we review our work on the Quaternary Gediz River Project (2001-2010) and present new data which leads to a revised stratigraphical model for the Early Pleistocene development of this fluvial system. In previous work we confirmed the preservation of eleven buried Early Pleistocene fluvial terraces of the Gediz River (designated GT11, the oldest and highest, to GT1, the youngest and lowest) which lie beneath the basalt-covered plateaux of the Kula Volcanic Province. Deciphering the information locked in this fluvial archive requires the construction of a robust geochronology. Fortunately, the Gediz archive provides ample opportunity for age-constraint based upon age estimates derived from basaltic lava flows that repeatedly entered the palaeo-Gediz valley floors. In this paper we present, for the first time, our complete dataset of 40Ar/39Ar age estimates and associated palaeomagnetic measurements. These data, which can be directly related to the underlying fluvial deposits, provide age constraints critical to our understanding of this sequence. The new chronology establishes the onset of Quaternary volcanism at ∼1320ka (MIS42). This volcanism, which is associated with GT6, confirms a pre-MIS42 age for terraces GT11-GT7. Evidence from the colluvial sequences directly overlying these early terraces suggests that they formed in response to hydrological and sediment budget changes forced by climate-driven vegetation change. The cyclic formation of terraces and their timing suggests they represent the obliquity-driven climate changes of the Early Pleistocene. By way of contrast the GT5-GT1 terrace sequence, constrained by a lava flow with an age estimate of ∼1247ka, span the time-interval MIS42 - MIS38 and therefore do not match the frequency of climate change as previously suggested. The onset of volcanism breaks the simple linkage of terracing to climate-driven change. These younger terraces more likely reflect a localized terracing process triggered by base level changes forced by volcanic eruptions and associated reactivation of pre-existing faults, lava dam construction, landsliding and subsequent lava-dammed lake drainage. Establishing a firm stratigraphy and geochronology for the Early Pleistocene archive provides a secure framework for future exploitation of this part of the archive and sets the standard as we begin our work on the Middle-Late Pleistocene sequence. We believe this work forms a benchmark study for detailed Quaternary research in Turkey.

  8. Measurement of the forward-backward asymmetry of $$\\Lambda$$ and $$\\bar{\\Lambda}$$ production in $$p \\bar{p}$$ collisions

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

    Abazov, Victor Mukhamedovich

    Here, we studymore » $$\\Lambda$$ and $$\\bar{\\Lambda}$$ production asymmetries in $$p \\bar{p} \\rightarrow \\Lambda (\\bar{\\Lambda}) X$$, $$p \\bar{p} \\rightarrow J/\\psi \\Lambda (\\bar{\\Lambda}) X$$, and $$p \\bar{p} \\rightarrow \\mu^\\pm \\Lambda (\\bar{\\Lambda}) X$$ events recorded by the D0 detector at the Fermilab Tevatron collider at $$\\sqrt{s} = 1.96$$ TeV. We find an excess of $$\\Lambda$$'s ($$\\bar{\\Lambda}$$'s) produced in the proton (antiproton) direction. This forward-backward asymmetry is measured as a function of rapidity. We confirm that the $$\\bar{\\Lambda}/\\Lambda$$ production ratio, measured by several experiments with various targets and a wide range of energies, is a universal function of "rapidity loss", i.e., the rapidity difference of the beam proton and the lambda.« less

  9. Measurement of the forward-backward asymmetry of $$\\Lambda$$ and $$\\bar{\\Lambda}$$ production in $$p \\bar{p}$$ collisions

    DOE PAGES

    Abazov, Victor Mukhamedovich

    2016-02-09

    Here, we studymore » $$\\Lambda$$ and $$\\bar{\\Lambda}$$ production asymmetries in $$p \\bar{p} \\rightarrow \\Lambda (\\bar{\\Lambda}) X$$, $$p \\bar{p} \\rightarrow J/\\psi \\Lambda (\\bar{\\Lambda}) X$$, and $$p \\bar{p} \\rightarrow \\mu^\\pm \\Lambda (\\bar{\\Lambda}) X$$ events recorded by the D0 detector at the Fermilab Tevatron collider at $$\\sqrt{s} = 1.96$$ TeV. We find an excess of $$\\Lambda$$'s ($$\\bar{\\Lambda}$$'s) produced in the proton (antiproton) direction. This forward-backward asymmetry is measured as a function of rapidity. We confirm that the $$\\bar{\\Lambda}/\\Lambda$$ production ratio, measured by several experiments with various targets and a wide range of energies, is a universal function of "rapidity loss", i.e., the rapidity difference of the beam proton and the lambda.« less

  10. Individual differences in the propensity to approach signals vs goals promote different adaptations in the dopamine system of rats.

    PubMed

    Flagel, Shelly B; Watson, Stanley J; Robinson, Terry E; Akil, Huda

    2007-04-01

    The way an individual responds to cues associated with rewards may be a key determinant of vulnerability to compulsive behavioral disorders. We studied individual differences in Pavlovian conditioned approach behavior and examined the expression of neurobiological markers associated with the dopaminergic system, the same neural system implicated in incentive motivational processes. Pavlovian autoshaping procedures consisted of the brief presentation of an illuminated retractable lever (conditioned stimulus) followed by the response-independent delivery of a food pellet (unconditioned stimulus), which lead to a Pavlovian conditioned response. In situ hybridization was performed on brains obtained either following the first or last (fifth) day of training. Two phenotypes emerged. Sign-trackers (ST) exhibited behavior that seemed to be largely controlled by the cue that signaled impending reward delivery; whereas goal-trackers (GT) preferentially approached the location where the reward was delivered. Following a single training session, ST showed greater expression of dopamine D1 receptor mRNA relative to GT. After 5 days of training, GT exhibited greater expression levels of tyrosine hydroxylase, dopamine transporter, and dopamine D2 receptor mRNA relative to ST. These findings suggest that the development of approach behavior towards signals vs goal leads to distinct adaptations in the dopamine system. The sign-tracker vs goal-tracker phenotype may prove to be a valuable animal model to investigate individual differences in the way incentive salience is attributed to environmental stimuli, which may contribute to the development of addiction and other compulsive behavioral disorders.

  11. An R2R3 MYB transcription factor determines red petal colour in an Actinidia (kiwifruit) hybrid population

    PubMed Central

    2013-01-01

    Background Red colour in kiwifruit results from the presence of anthocyanin pigments. Their expression, however, is complex, and varies among genotypes, species, tissues and environments. An understanding of the biosynthesis, physiology and genetics of the anthocyanins involved, and the control of their expression in different tissues, is required. A complex, the MBW complex, consisting of R2R3-MYB and bHLH transcription factors together with a WD-repeat protein, activates anthocyanin 3-O-galactosyltransferase (F3GT1) to produce anthocyanins. We examined the expression and genetic control of anthocyanins in flowers of Actinidia hybrid families segregating for red and white petal colour. Results Four inter-related backcross families between Actinidia chinensis Planch. var. chinensis and Actinidia eriantha Benth. were identified that segregated 1:1 for red or white petal colour. Flower pigments consisted of five known anthocyanins (two delphinidin-based and three cyanidin-based) and three unknowns. Intensity and hue differed in red petals from pale pink to deep magenta, and while intensity of colour increased with total concentration of anthocyanin, no association was found between any particular anthocyanin data and hue. Real time qPCR demonstrated that an R2R3 MYB, MYB110a, was expressed at significant levels in red-petalled progeny, but not in individuals with white petals. A microsatellite marker was developed that identified alleles that segregated with red petal colour, but not with ovary, stamen filament, or fruit flesh colour in these families. The marker mapped to chromosome 10 in Actinidia. The white petal phenotype was complemented by syringing Agrobacterium tumefaciens carrying Actinidia 35S::MYB110a into the petal tissue. Red pigments developed in white petals both with, and without, co-transformation with Actinidia bHLH partners. MYB110a was shown to directly activate Actinidia F3GT1 in transient assays. Conclusions The transcription factor, MYB110a, regulates anthocyanin production in petals in this hybrid population, but not in other flower tissues or mature fruit. The identification of delphinidin-based anthocyanins in these flowers provides candidates for colour enhancement in novel fruits. PMID:23324587

  12. Event-specific plasmid standards and real-time PCR methods for transgenic Bt11, Bt176, and GA21 maize and transgenic GT73 canola.

    PubMed

    Taverniers, Isabel; Windels, Pieter; Vaïtilingom, Marc; Milcamps, Anne; Van Bockstaele, Erik; Van den Eede, Guy; De Loose, Marc

    2005-04-20

    Since the 18th of April 2004, two new regulations, EC/1829/2003 on genetically modified food and feed products and EC/1830/2003 on traceability and labeling of GMOs, are in force in the EU. This new, comprehensive regulatory framework emphasizes the need of an adequate tracing system. Unique identifiers, such as the transgene genome junction region or a specific rearrangement within the transgene DNA, should form the basis of such a tracing system. In this study, we describe the development of event-specific tracing systems for transgenic maize lines Bt11, Bt176, and GA21 and for canola event GT73. Molecular characterization of the transgene loci enabled us to clone an event-specific sequence into a plasmid vector, to be used as a marker, and to develop line-specific primers. Primer specificity was tested through qualitative PCRs and dissociation curve analysis in SYBR Green I real-time PCRs. The primers were then combined with event-specific TaqMan probes in quantitative real-time PCRs. Calibration curves were set up both with genomic DNA samples and the newly synthesized plasmid DNA markers. It is shown that cloned plasmid GMO target sequences are perfectly suitable as unique identifiers and quantitative calibrators. Together with an event-specific primer pair and a highly specific TaqMan probe, the plasmid markers form crucial components of a unique and straighforward tracing system for Bt11, Bt176, and GA21 maize and GT73 canola events.

  13. Dietary Intervention of Artemisia and Green Tea Extracts to Rejuvenate Helicobacter pylori-Associated Chronic Atrophic Gastritis and to Prevent Tumorigenesis.

    PubMed

    Jeong, Migyeong; Park, Jong-Min; Han, Young-Min; Kangwan, Napapan; Kwon, Sang-Oh; Kim, Bok-Nam; Kim, Won-Hee; Hahm, Ki-Baik

    2016-02-01

    As nonmicrobial dietary approach is capable of controlling Helicobacter pylori infection, we evaluated the efficacy of long-term dietary administration of Artemisia and/or green tea extracts on H. pylori-initiated, high-salt-promoted chronic atrophic gastritis and gastric tumorigenesis mouse model. Helicobacter pylori-infected and high-salt-diet-administered C57BL/6 mice were administered with Artemisia extracts (MP group) and/or green tea extracts (GT group) for 36 weeks in addition to the control group (ES group, gastroprotective drug, ecabet sodium 30 mg/kg, diet pellet). Gross and pathological gastric lesions were evaluated after 24 and 36 weeks, respectively, and their underlying molecular changes were measured in gastric homogenates. Detailed mechanisms were further evaluated in in vitro cell models. The erythematous and nodular changes and mucosal ulcerative and erosive lesions were noted in the control group at 24 weeks. MP, GT, MPGT, and ES groups all showed significantly ameliorated pathologic lesion compared to the control group (p < .05). After the 36 weeks, scattered nodular masses with some central ulcers and thin gastric surface were noted in the control stomach, whereas no tumorous lesion and milder atrophic changes were observed in all MP, GT, and MPGT groups except ES group (p < .05). On molecular analysis, increased expressions of COX-2, TNF-α, IL-6, lipid peroxide, and activated STAT3 relevant to H. pylori infection were significantly decreased with MPGT administration (p < .01), whereas HSP70 was significantly increased. PGDH expressions, core tumor suppressor involved in carcinogenesis, were significantly decreased with H. pylori infection (p < .05), but significantly increased in MPGT group (p < .05). Increased mucosal apoptotic index noted in the control group was significantly decreased with MP and/or GT along with significantly preserved gastric gastroprotective mediators (p < .01) such as mucins, HSP27, and HSP70. H. pylori-induced serum TNF-α and NF-κB activations were significantly decreased with MPGT administration (p < .05). Long-term dietary intake of MP and/or GT can be an effective strategy either to rejuvenate H. pylori atrophic gastritis or to suppress tumorigenesis. © 2015 John Wiley & Sons Ltd.

  14. GORDON, RICHARD F., ASTRONAUT - TRAINING - GEMINI-TITAN (GT)-11 - WATER EGRESS - GULF

    NASA Image and Video Library

    1966-07-23

    S66-44497 (23 July 1966) --- Astronauts Charles Conrad Jr. (left) and Richard F. Gordon Jr. (right), prime crew for the Gemini-11 spaceflight, practice water egress procedures in the Gulf of Mexico. Static Article 5 was used in the training exercise. A MSC swimmer is in the water assisting in the training. Photo credit: NASA

  15. Functional Comparison of Induced Pluripotent Stem Cell- and Blood-Derived GPIIbIIIa Deficient Platelets

    PubMed Central

    Haas, Jessica; Sandrock-Lang, Kirstin; Gärtner, Florian; Jung, Christian Billy; Zieger, Barbara; Parrotta, Elvira; Kurnik, Karin; Sinnecker, Daniel; Wanner, Gerhard; Laugwitz, Karl-Ludwig; Massberg, Steffen; Moretti, Alessandra

    2015-01-01

    Human induced pluripotent stem cells (hiPSCs) represent a versatile tool to model genetic diseases and are a potential source for cell transfusion therapies. However, it remains elusive to which extent patient-specific hiPSC-derived cells functionally resemble their native counterparts. Here, we generated a hiPSC model of the primary platelet disease Glanzmann thrombasthenia (GT), characterized by dysfunction of the integrin receptor GPIIbIIIa, and compared side-by-side healthy and diseased hiPSC-derived platelets with peripheral blood platelets. Both GT-hiPSC-derived platelets and their peripheral blood equivalents showed absence of membrane expression of GPIIbIIIa, a reduction of PAC-1 binding, surface spreading and adherence to fibrinogen. We demonstrated that GT-hiPSC-derived platelets recapitulate molecular and functional aspects of the disease and show comparable behavior to their native counterparts encouraging the further use of hiPSC-based disease models as well as the transition towards a clinical application. PMID:25607928

  16. Pyrethroid insecticide lambda-cyhalothrin and its metabolites induce liver injury through the activation of oxidative stress and proinflammatory gene expression in rats following acute and subchronic exposure.

    PubMed

    Aouey, Bakhta; Derbali, Mohamed; Chtourou, Yassine; Bouchard, Michèle; Khabir, Abdelmajid; Fetoui, Hamadi

    2017-02-01

    Lambda-cyhalothrin (LTC) [α-cyano-3-phenoxybenzyl-3-(2-chloro-3,3,3-trifluoro-1-propenyl)-2,2-dimethylcyclo-propanecarboxylate] is a synthetic type II pyrethroid insecticide commonly used in residential and agricultural areas. The potential hepatotoxicity of pyrethroids remains unclear and could easily be assessed by measuring common clinical indicators of liver disease. To understand more about the potential risks for humans associated with LTC exposure, male adult rats were orally exposed to 6.2 and 31.1 mg/kg bw of LTC for 7, 30, 45, and 60 days. Histopathological changes and alterations of main parameters related to oxidative stress and inflammatory responses in the liver were evaluated. Further, lambda-cyhalothrin metabolites [3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethyl-cyclopropane carboxylic acid (CFMP), 4-hydroxyphenoxybenzoic acid (4-OH-3-PBA), and 3-phenoxybenzoic acid (3-PBA)] in the liver tissues were identified and quantified by ultra-high-performance liquid chromatography coupled to quadripole time-of-flight mass spectrometry (UHPLC-MS-Q-ToF). Results revealed that LTC exposure significantly increased markers of hepatic oxidative stress in a time-dependent and dose-dependent manner, and this was associated with an accumulation of CFMP and 3-PBA in the liver tissues. In addition, the levels of tumor necrosis factor-α (TNF-α) and interleukin (IL-6 and IL-1β) gene expressions were significantly increased in the liver of exposed rats compared to controls. Correlation analyses revealed that CFMP and 3-PBA metabolite levels in the liver tissues were significantly correlated with the indexes of oxidative stress, redox status, and inflammatory markers in rats exposed to lambda-cyhalothin. Overall, this study provided novel evidence that hepatic damage is likely due to increased oxidative stress and inflammation under the condition of acute and subchronic exposure to lambda-cyhalothrin and that LTC metabolites (CFMP and 3-PBA) could be used as potential biomarker in human biomonitoring studies.

  17. Seed-Specific Expression of OsDWF4, a Rate-Limiting Gene Involved in Brassinosteroids Biosynthesis, Improves Both Grain Yield and Quality in Rice.

    PubMed

    Li, Qian-Feng; Yu, Jia-Wen; Lu, Jun; Fei, Hong-Yuan; Luo, Ming; Cao, Bu-Wei; Huang, Li-Chun; Zhang, Chang-Quan; Liu, Qiao-Quan

    2018-04-18

    Brassinosteroids (BRs) are essential plant-specific steroidal hormones that regulate diverse growth and developmental processes in plants. We evaluated the effects of OsDWF4, a gene that encodes a rate-limiting enzyme in BR biosynthesis, on both rice yield and quality when driven by the Gt1 or Ubi promoter, which correspond to seed-specific or constitutive expression, respectively. Generally, transgenic plants expressing OsDWF4 showed increased grain yield with more tillers and longer and heavier seeds. Moreover, the starch physicochemical properties of the transgenic rice were also improved. Interestingly, OsDWF4 was found to exert different effects on either rice yield or quality when driven by the different promoters. The overall performance of the pGt1::OsDWF4 lines was better than that of the pUbi::OsDWF4 lines. Our data not only demonstrate the effects of OsDWF4 overexpression on both rice yield and quality but also suggest that a seed-specific promoter is a good choice in BR-mediated rice breeding programs.

  18. DSN G/T(sub op) and telecommunications system performance

    NASA Technical Reports Server (NTRS)

    Stelzried, C.; Clauss, R.; Rafferty, W.; Petty, S.

    1992-01-01

    Provided here is an intersystem comparison of present and evolving Deep Space Network (DSN) microwave receiving systems. Comparisons of the receiving systems are based on the widely used G/T sub op figure of merit, which is defined as antenna gain divided by operating system noise temperature. In 10 years, it is expected that the DSN 32 GHz microwave receiving system will improve the G/T sub op performance over the current 8.4 GHz system by 8.3 dB. To compare future telecommunications system end-to-end performance, both the receiving systems' G/T sub op and spacecraft transmit parameters are used. Improving the 32 GHz spacecraft transmitter system is shown to increase the end-to-end telecommunications system performance an additional 3.2 dB, for a net improvement of 11.5 dB. These values are without a planet in the field of view (FOV). A Saturn mission is used for an example calculation to indicate the degradation in performance with a planet in the field of view.

  19. Redox-linked effects of green tea on DNA damage and repair, and influence of microsatellite polymorphism in HMOX-1: results of a human intervention trial.

    PubMed

    Choi, Siu-Wai; Yeung, Vincent T F; Collins, Andrew R; Benzie, Iris F F

    2015-01-01

    Green tea has many reported health benefits, including genoprotective and antioxidant effects, but green tea has pro-oxidant activity in vitro. A tea-induced pro-oxidant shift that triggers cytoprotective adaptations has been postulated, but human data are lacking. We investigated effects on oxidation-induced DNA damage and redox-linked cytoprotective factors, including 8-oxoguanine glycosylase (hOGG1) and heme oxygenase 1 (HMOX-1) in lymphocytes in a randomised, placebo-controlled, cross-over supplementation trial. hOGG1 catalyses the first step in base excision repair; increased HMOX-1 is a sign of cytoprotective response to pro-oxidant change. The influence of microsatellite polymorphisms in the HMOX-1 promoter region was also explored. Higher numbers of GT repeats [GT(n)] in this region reportedly diminish response to pro-oxidant change. Green tea [2 × 150 ml of 1% w/v tea/day (or water as control)] was taken for 12 weeks by 43 Type 2 diabetes subjects {20 with short [S/S; GT(n) < 25] and 23 with long [L/L; GT(n) ≥ 25]}. Fasting venous blood was collected before and after each treatment. The formamidopyrimidine DNA glycosylase-assisted comet assay was used to measure DNA damage in lymphocytes. For measuring hOGG1 activity, we used photo-damaged HeLa cells incubated with lymphocyte extracts from test subjects, in combination with the comet assay. Lymphocyte HMOX-1 and hOGG1 protein concentrations and expression (mRNA) of redox-sensitive genes, including HMOX-1 and hOGG1, were also investigated. Results showed significantly (P < 0.01) lower (~15%) DNA damage, higher (~50%) hOGG1 activity and higher (~40%) HMOX-1 protein concentration after tea. No changes in mRNA expression were seen. Baseline HMOX-1 protein and hOGG1 activity were higher (P < 0.05) in the S/S group, but tea-associated responses were similar in both GT(n) groups. Green tea is clearly associated with lowered DNA damage, increased hOGG1 activity and higher HMOX-1 protein levels. Further study is needed to confirm a cause and effect relationship and to establish if these effects are mediated by post-translational changes in proteins or by increased gene expression. © The Author 2014. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Transcriptome sequencing of a chimaera reveals coordinated expression of anthocyanin biosynthetic genes mediating yellow formation in herbaceous peony (Paeonia lactiflora Pall.).

    PubMed

    Zhao, Daqiu; Jiang, Yao; Ning, Chuanlong; Meng, Jiasong; Lin, Shasha; Ding, Wen; Tao, Jun

    2014-08-19

    Herbaceous peony (Paeonia lactiflora Pall.) is a traditional flower in China and a wedding attractive flower in worldwide. In its flower colour, yellow is the rarest which is ten times the price of the other colours. However, the breeding of new yellow P. lactiflora varieties using genetic engineering is severely limited due to the little-known biochemical and molecular mechanisms underlying its characteristic formation. In this study, two cDNA libraries generated from P. lactiflora chimaera with red outer-petal and yellow inner-petal were sequenced using an Illumina HiSeq™ 2000 platform. 66,179,398 and 65,481,444 total raw reads from red outer-petal and yellow inner-petal cDNA libraries were generated, which were assembled into 61,431 and 70,359 Unigenes with an average length of 628 and 617 nt, respectively. Moreover, 61,408 non-redundant All-unigenes were obtained, with 37,511 All-unigenes (61.08%) annotated in public databases. In addition, 6,345 All-unigenes were differentially expressed between the red outer-petal and yellow inner-petal, with 3,899 up-regulated and 2,446 down-regulated All-unigenes, and the flavonoid metabolic pathway related to colour development was identified using the Kyoto encyclopedia of genes and genomes database (KEGG). Subsequently, the expression patterns of 10 candidate differentially expressed genes (DEGs) involved in the flavonoid metabolic pathway were examined, and flavonoids were qualitatively and quantitatively analysed. Numerous anthoxanthins (flavone and flavonol) and a few anthocyanins were detected in the yellow inner-petal, which were all lower than those in the red outer-petal due to the low expression levels of the phenylalanine ammonialyase gene (PlPAL), flavonol synthase gene (PlFLS), dihydroflavonol 4-reductase gene (PlDFR), anthocyanidin synthase gene (PlANS), anthocyanidin 3-O-glucosyltransferase gene (Pl3GT) and anthocyanidin 5-O-glucosyltransferase gene (Pl5GT). Transcriptome sequencing (RNA-Seq) analysis based on the high throughput sequencing technology was an efficient approach to identify critical genes in P. lactiflora and other non-model plants. The flavonoid metabolic pathway and glucide metabolic pathway were identified as relatived yellow formation in P. lactiflora, PlPAL, PlFLS, PlDFR, PlANS, Pl3GT and Pl5GT were selected as potential candidates involved in flavonoid metabolic pathway, which inducing inhibition of anthocyanin biosynthesis mediated yellow formation in P. lactiflora. This study could lay a theoretical foundation for breeding new yellow P. lactiflora varieties.

  1. Effect of dysprosium and lutetium metal buffer layers on the resistive switching characteristics of Cu-Sn alloy-based conductive-bridge random access memory.

    PubMed

    Vishwanath, Sujaya Kumar; Woo, Hyunsuk; Jeon, Sanghun

    2018-06-18

    Conductive-bridge random access memory (CBRAM) has become one of the most suitable candidates for non-volatile memory in next-generation information and communication technology. The resistive switching mechanism of CBRAM depends on the formation/annihilation of the conductive filament (CF) between the active metal electrode and the inert electrode. However, excessive ion injection from the active electrode into the solid electrolyte is reduces the uniformity and reliability of the resistive switching devices. To solve this problem, we investigated the resistive switching characteristics of a modified active electrode with different compositions of Cu<sub>x</sub>-Sn<sub><sub>1-x </sub></sub>(0.13 < X < 0.55). The resistive switching characteristics were further improved by inserting a dysprosium (Dy) or lutetium (Lu) buffer layer at the interface of Cu<sub>x</sub>-Sn<sub>1-x</sub>/Al<sub>2</sub>O<sub>3</sub>. Electrical analysis of the optimal Cu<sub>0.27</sub>-Sn<sub>0.73</sub>/Lu-based CBRAM exhibited stable resistive switching behavior with low operation voltage (SET: 0.7 V and RESET: -0.3 V), a high on/off resistive ratio (10<sup>6</sup>), cyclic endurance (>10<sup>4</sup>), and long-term retention (85℃/10 years). To achieve these performance parameters, CFs were locally formed inside the electrolyte using a modified CuSn active electrode, and the amount of Cu-ion injection was reduced by inserting the Dy or Lu buffer layer between the CuSn active electrode and the electrolyte. In particular, conductive-atomic force microscopy results at the Dy/ or Lu/Al<sub>2</sub>O<sub>3</sub> interface directly showed and defined the diameter of the CF. © 2018 IOP Publishing Ltd.

  2. Interaction between DRD2 variation and sound environment on mood and emotion-related brain activity.

    PubMed

    Quarto, T; Fasano, M C; Taurisano, P; Fazio, L; Antonucci, L A; Gelao, B; Romano, R; Mancini, M; Porcelli, A; Masellis, R; Pallesen, K J; Bertolino, A; Blasi, G; Brattico, E

    2017-01-26

    Sounds, like music and noise, are capable of reliably affecting individuals' mood and emotions. However, these effects are highly variable across individuals. A putative source of variability is genetic background. Here we explored the interaction between a functional polymorphism of the dopamine D2 receptor gene (DRD2 rs1076560, G>T, previously associated with the relative expression of D2S/L isoforms) and sound environment on mood and emotion-related brain activity. Thirty-eight healthy subjects were genotyped for DRD2 rs1076560 (G/G=26; G/T=12) and underwent functional magnetic resonance imaging (fMRI) during performance of an implicit emotion-processing task while listening to music or noise. Individual variation in mood induction was assessed before and after the task. Results showed mood improvement after music exposure in DRD2GG subjects and mood deterioration after noise exposure in GT subjects. Moreover, the music, as opposed to noise environment, decreased the striatal activity of GT subjects as well as the prefrontal activity of GG subjects while processing emotional faces. These findings suggest that genetic variability of dopamine receptors affects sound environment modulations of mood and emotion processing. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Measurements of J/{psi} and {psi}(2S) decays into {lambda}{lambda}{pi}{sup 0} and {lambda}{lambda}{eta}

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

    Ablikim, M.; Bai, J. Z.; Cai, X.

    2007-11-01

    Using 58x10{sup 6} J/{psi} and 14x10{sup 6} {psi}(2S) events collected by the BESII detector at the BEPC, branching fractions or upper limits for the decays J/{psi} and {psi}(2S){yields}{lambda}{lambda}{pi}{sup 0} and {lambda}{lambda}{eta} are measured. For the isospin violating decays, the upper limits are determined to be B(J/{psi}{yields}{lambda}{lambda}{pi}{sup 0})<6.4x10{sup -5} and B[{psi}(2S){yields}{lambda}{lambda}{pi}{sup 0}]<4.9x10{sup -5} at the 90% confidence level. The isospin conserving process J/{psi}{yields}{lambda}{lambda}{eta} is observed for the first time, and its branching fraction is measured to be B(J/{psi}{yields}{lambda}{lambda}{eta})=(2.62{+-}0.60{+-}0.44)x10{sup -4}, where the first error is statistical and the second one is systematic. No {lambda}{lambda}{eta} signal is observed in {psi}(2S) decays, and B[{psi}(2S){yields}{lambda}{lambda}{eta}]<1.2x10{supmore » -4} is set at the 90% confidence level. Branching fractions of J/{psi} decays into {sigma}{sup +}{pi}{sup -}{lambda} and {sigma}{sup -}{pi}{sup +}{lambda} are also reported, and the sum of these branching fractions is determined to be B(J/{psi}{yields}{sigma}{sup +}{pi}{sup -}{lambda}+c.c.)=(1.52{+-}0.08{+-}0.16)x10{sup -3}.« less

  4. Study of B{yields}{lambda}{sub c}{lambda}{sub c} and B{yields}{lambda}{sub c}{lambda}{sub c}K

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

    Cheng, H.-Y.; Hsiao, Y.-K.; Chua, C.-K.

    2009-06-01

    We study the doubly charmful two-body and three-body baryonic B decays B{yields}{lambda}{sub c}{sup +}{lambda}{sub c}{sup -} and B{yields}{lambda}{sub c}{sup +}{lambda}{sub c}{sup -}K. As pointed out before, a naive estimate of the branching ratio O(10{sup -8}) for the latter decay is too small by 3 to 4 orders of magnitude compared to experiment. Previously, it has been shown that a large enhancement for the {lambda}{sub c}{sup +}{lambda}{sub c}{sup -}K production can occur due to a charmoniumlike resonance (e.g. X(4630) discovered by Belle) with a mass near the {lambda}{sub c}{lambda}{sub c} threshold. Motivated by the BABAR's observation of a resonance in themore » {lambda}{sub c}K system with a mass of order 2930 MeV, we study in this work the contribution to B{yields}{lambda}{sub c}{sup +}{lambda}{sub c}{sup -}K from the intermediate state {xi}{sub c}(2980) which is postulated to be a first positive-parity excited D-wave charmed baryon state. Assuming that a soft qq quark pair is produced through the {sigma} and {pi} meson exchanges in the configuration for B{yields}{xi}{sub c}(2980){lambda}{sub c} and {lambda}{sub c}{lambda}{sub c}, it is found that branching ratios of B{yields}{lambda}{sub c}{sup +}{lambda}{sub c}{sup -}K and B{yields}{lambda}{sub c}{sup +}{lambda}{sub c}{sup -} are of order 3.5x10{sup -4} and 5x10{sup -5}, respectively, in agreement with experiment except that the prediction for the {lambda}{sub c}{lambda}{sub c}K{sup -} is slightly smaller. In conjunction with our previous analysis, we conclude that the enormously large rate of B{yields}{lambda}{sub c}{sup +}{lambda}{sub c}{sup -}K arises from the resonances {xi}{sub c}(2980) and X(4630)« less

  5. Study of genetic effects of high energy radiations with different ionizing capacities on extracellular phages.

    PubMed

    Bresler, S E; Kalinin, V L; Kopylova, Y U; Krivisky, A S; Rybchin, V N; Shelegedin, V N

    1975-07-01

    The inactivating and mutagenic action of high-energy radiations with different ionizing capacities (gamma-rays, protons, alpha-particles and accelerated ions of 12C and 20Ne) was studied by using coliphages lambda11 and SD as subjects. In particular the role of irradiation conditions (broth suspension, pure buffer, dry samples) and of the host functions recA, exrA and polA was investigated. The dose-response curve of induced mutagenesis was studied by measuring the yield of vir mutants in lambda11 and plaque mutants in SD. The following results were obtained. (1) The inactivation kinetics of phages under the action of gamma-rays and protons was first order to a survival of 10(-7). Heavy ions also showed exponential inactivation kinetics to a survival of 10(-4). At higher doses of 20Ne ion bombardment some deviation from one-hit kinetics was observed. For dry samples of phages the dimensions of targets for all types of radiation were approximately proportional to the molecular weights of phage DNA's. For densely ionizing radiation (heavy ions) the inactivating action was 3-5 times weaker than for gamma-rays and protons. (2) Mutagenesis was observed for all types of radiation, but heavy ions were 1-5-2 times less efficient than gamma-rays. For both phages studied the dose-response curve of mutagenesis was non-linear. The dependence on the dose was near to parabolic for lambda11. For SD a plateau or maximum of mutagenesis was observed for the relative number of mutants at a survival of about 10(-4). (3) Host-cell functions recA and exrA were practically indifferent for survival of gamma-irradiated phage lambda11, but indispensable for mutagenesis. Mutation recAI3 abolished induced vir mutations totally and exrA- reduced them significantly. The absence of the function polA had a considerable influence on phage survival, but no effect on vir mutation yield (if compared at the same survival level). (4) In conditions of indirect action of gamma-rays no vir mutations were induced. This is regarded as evidence that the single-strand breaks formed under indirect action conditions cannot serve as pre-mutational damage in DNA.

  6. Pendulating-A grounded theory explaining patients' behavior shortly after having a leg amputated due to vascular disease.

    PubMed

    Madsen, Ulla Riis; Hommel, Ami; Bååth, Carina; Berthelsen, Connie Bøttcher

    2016-01-01

    Although the group of vascular leg amputated patients constitutes some of the most vulnerable and frail on the orthopedic wards, previous research of amputated patients has focused on patients attending gait training in rehabilitation facilities leaving the patient experience shortly after surgery unexplored. Understanding patients' behavior shortly after amputation could inform health professionals in regard to how these vulnerable patients' needs at hospital can be met as well as how to plan for care post-discharge. To construct a grounded theory (GT) explaining patients' behavior shortly after having a leg amputated as a result of vascular disease. In line with constructivist GT methodology, data from ethnographic observations and interviews were simultaneously collected and analyzed using the constant comparative method covering the patients' experiences during the first 4 weeks post-surgery. Data collection was guided by theoretical sampling and comprised 11 patients. A GT was constructed. Patients went through a three-phased process as they realized they were experiencing a life-changing event. The first phase was "Losing control" and comprised the sub-categories "Being overwhelmed" and "Facing dependency." The second phase was "Digesting the shock" and comprised the sub-categories "Swallowing the life-changing decision," "Detecting the amputated body" and "Struggling dualism." The third phase was "Regaining control" and comprised the sub-categories "Managing consequences" and "Building-up hope and self-motivation." "Pendulating" was identified as the core category describing the general pattern of behavior and illustrated how patients were swinging both cognitively and emotionally throughout the process. The theory of "Pendulating" offers a tool to understand the amputated patients' behavior and underlying concerns and to recognize where they are in the process. Concepts from the theory could be used by health professionals who support patients coping with the situation by offering terms to express and recognize patients' reactions.

  7. Identification of flavonoids and expression of flavonoid biosynthetic genes in two coloured tree peony flowers.

    PubMed

    Zhao, Daqiu; Tang, Wenhui; Hao, Zhaojun; Tao, Jun

    2015-04-10

    Tree peony (Paeonia suffruticosa Andr.) has been named the "king of flowers" because of its elegant and gorgeous flower colour. Among these colours, the molecular mechanisms of white formation and how white turned to red in P. suffruticosa is little known. In this study, flower colour variables, flavonoid accumulation and expression of flavonoid biosynthetic genes of white ('Xueta') and red ('Caihui') P. suffruticosa were investigated. The results showed that the flower colours of both cultivars were gradually deepened with the development of flowers. Moreover, two anthoxanthin compositions apigenin 7-O-glucoside together with apigenin deoxyheso-hexoside were identified in 'Xueta' and 'Caihui', but one main anthocyanin composition peonidin 3,5-di-O-glucoside (Pn3G5G) was only found in 'Caihui'. Total contents of anthocyanins in 'Caihui' was increased during flower development, and the same trend was presented in anthoxanthins and flavonoids of these two cultivars, but the contents of these two category flavonoid in 'Caihui' were always higher than those in 'Xueta'. Furthermore, nine structural genes in flavonoid biosynthetic pathway were isolated including the full-length cDNAs of phenylalanine ammonialyase gene (PAL), chalcone synthase gene (CHS) and chalcone isomerase gene (CHI), together with the partial-length cDNAs of flavanone 3-hydroxylase gene (F3H), flavonoid 3'-hydroxylase gene (F3'H), dihydroflavonol 4-reductase gene (DFR), anthocyanidin synthase gene (ANS), UDP-glucose: flavonoid 3-O-glucosyltransferase gene (UF3GT) and UDP-glucose: flavonoid 5-O-glucosyltransferase gene (UF5GT), and PAL, UF3GT and UF5GT were reported in P. suffruticosa for the first time. Their expression patterns showed that transcription levels of downstream genes in 'Caihui' were basically higher than those in 'Xueta', especially PsDFR and PsANS, suggesting that these two genes may play a key role in the anthocyanin biosynthesis which resulted in the shift from white to red in flowers. These results would provide a better understanding of the underlying molecular mechanisms of flower pigmentation in P. suffruticosa. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Measurement of the $$\\Lambda_b$$ cross section and the $$_{\\bar{\\Lambda}_b}$$ to $$\\Lambda_b$$ ratio with $$J/\\Psi \\Lambda$$ decays in $pp$ collisions at $$\\sqrt{s}=7$$ TeV

    DOE PAGES

    Chatrchyan, Serguei; et al.

    2013-07-16

    The Lambda(b) differential production cross section and the cross section ratio anti-Lambda(b)/Lambda(b) are measured as functions of transverse momentum pt(Lambda(b)) and rapidity abs(y(Lambda(b))) in pp collisions at sqrt(s) = 7 TeV using data collected by the CMS experiment at the LHC. The measurements are based on Lambda(b) decays reconstructed in the exclusive final state J/Psi Lambda, with the subsequent decays J/Psi to an opposite-sign muon pair and Lambda to proton pion, using a data sample corresponding to an integrated luminosity of 1.9 inverse femtobarns. The product of the cross section times the branching ratio for Lambda(b) to J/Psi Lambda versusmore » pt(Lambda(b)) falls faster than that of b mesons. The measured value of the cross section times the branching ratio for pt(Lambda(b)) > 10 GeV and abs(y(Lambda(b))) < 2.0 is 1.06 +/- 0.06 +/- 0.12 nb, and the integrated cross section ratio for anti-Lambda(b)/Lambda(b) is 1.02 +/- 0.07 +/- 0.09, where the uncertainties are statistical and systematic, respectively.« less

  9. The control of lambda DNA terminase synthesis.

    PubMed Central

    Murialdo, H; Davidson, A; Chow, S; Gold, M

    1987-01-01

    Nu1 and A, the genes coding for bacteriophage lambda DNA terminase, rank among the most poorly translated genes expressed in E. coli. To understand the reason for this low level of translation the genes were cloned into plasmids and their expression measured. In addition, the wild type DNA sequences immediately preceding the genes were reduced and modified. It was found that the elements that control translation are contained in the 100 base pairs upstream from the initiation codon. Interchanging these upstream sequences with those of an efficiently translated gene dramatically increased the translation of terminase subunits. It seems unlikely that the rare codons present in the genes, and any feature of their mRNA secondary structure play a role in the control of their translation. The elimination of cos from plasmids containing Nu1 and A also resulted in an increase in terminase production. This result suggests a role for cos in the control of late gene expression. The terminase subunit overproducer strains are potentially very useful for the design of improved DNA packaging and cosmid mapping techniques. Images PMID:3029667

  10. Switch from hapten-specific immunoglobulin M to immunoglobulin D secretion in a hybrid mouse cell line.

    PubMed Central

    Neuberger, M S; Rajewsky, K

    1981-01-01

    From a hybrid mouse cell line (B1-8) that secreted an IgM, lambda 1 anti-(4-hydroxy-3-nitrophenyl)acetyl antibody but that had no detectable surface IgM, selection for a variant with lambda 1 chains on the surface resulted in the isolation of a line that had switched from mu to delta expression. The surface and secreted Igs of this line were typed as IgD with two monoclonal antibodies, and the parental IgM and variant IgD molecules carried the same variable regions as judged by hapten-binding and idiotypic analysis. The surface and secreted delta chains of the IgD variant have apparent molecular weights of 64,000 and 61,000, respectively. However, the unglycosylated secreted delta polypeptide chain has a molecular weight of only 44,000. The secreted IgD exists predominantly in the delta 2 lambda A2 form, does not contain J protein, is relatively stable in serum, and does not fix complement. Images PMID:6940132

  11. Comparison of the nutrient and chemical contents of traditional Korean Chungtaejeon and green teas.

    PubMed

    Park, Yong-Seo; Lee, Mi-Kyung; Heo, Buk-Gu; Ham, Kyung-Sik; Kang, Seong-Gook; Cho, Ja-Yong; Gorinstein, Shela

    2010-06-01

    This study was conducted in order to compare the nutrient and chemical contents of two Korean teas: traditional Chungtaejeon tea (CTJ) with that of green tea (GT). Main bioactive compounds and the antioxidant activities using four radical scavenging assays (ABTS, CUPRAC, FRAP and DPPH) in methanol and acetone extracts of both teas were determined. It was found that the contents of vitamin C, amino acids and total nitrogen in CTJ were lower than that of GT (p < 0.05). Caffeine, reducing sugar and chlorophyll contents in CTJ were similar to GT. Catechin (C), epicatechin (EC), and epigallocatechin (EGC) contents were lower in CTJ than in green tea (p < 0.05), but gallocatechin (GC), epicatechin gallate (ECG), epigallocatechin gallate (EGCG) and catechin gallate (CG) showed no significant differences between CTJ and GT (p >/= 0.05). The contents of polyphenols, flavonoids, flavanols and tannins in CTJ methanol were 229.30 +/- 11.3 mg GAE/g dry weight (DW), 15.24 +/- 0.8 mg CE/g DW, 109.10 +/- 5.1 mg CE/g DW and 25.68 +/- 1.2 mg CE/g DW, respectively, and significantly higher than in acetone extracts (p < 0.05). Flavonoids (quercetin and kaempferol) were higher in GT than in CTJ and myricetin was higher in CTJ (p < 0.05). Threonine and aspartic acid was lower, and glutamic acid was higher in CTJ compared with GT (p < 0.05). Free amino acid content in CTJ and GT showed no significant difference. Potassium and magnesium in CTJ were lower compared to GT, but no significant difference was found for iron, manganese and calcium. Also, the level of the antioxidant activity by all four used assays was significantly higher in CTJ and in methanol was higher than in acetone extracts (p < 0.05). In conclusion, traditional fermented Korean tea Chungtaejeon contains high quantities of bioactive compounds and possesses high antioxidant activity. The contents of the bioactive compounds and the levels of antioxidant activities are significantly higher in methanol than in acetone extracts. 3-D fluorescence and FTIR- spectroscopy showed slight differences between the two investigated tea samples and can be used as additional tools for identification of polyphenols. Both studied teas can be recommended as a source of bioactive compounds.

  12. Measurement of trilinear gauge boson couplings from WW+WZ{yields}l{nu}jj events in pp collisions at {radical}(s)=1.96 TeV

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

    Abazov, V. M.; Alexeev, G. D.; Kharzheev, Y. N.

    2009-09-01

    We present a direct measurement of trilinear gauge boson couplings at {gamma}WW and ZWW vertices in WW and WZ events produced in pp collisions at {radical}(s)=1.96 TeV. We consider events with one electron or muon, missing transverse energy, and at least two jets. The data were collected using the D0 detector and correspond to 1.1 fb{sup -1} of integrated luminosity. Considering two different relations between the couplings at the {gamma}WW and ZWW vertices, we measure these couplings at 68% C.L. to be {kappa}{sub {gamma}}=1.07{sub -0.29}{sup +0.26}, {lambda}=0.00{sub -0.06}{sup +0.06}, and g{sub 1}{sup Z}=1.04{sub -0.09}{sup +0.09} in a scenario respecting SU(2){submore » L} x U(1){sub Y} gauge symmetry and {kappa}=1.04{sub -0.11}{sup +0.11} and {lambda}=0.00{sub -0.06}{sup +0.06} in an 'equal couplings' scenario.« less

  13. Derivation of the cut-off length from the quantum quadratic enhancement of a mass in vacuum energy constant Lambda

    NASA Astrophysics Data System (ADS)

    Fukushima, Kimichika; Sato, Hikaru

    2018-04-01

    Ultraviolet self-interaction energies in field theory sometimes contain meaningful physical quantities. The self-energies in such as classical electrodynamics are usually subtracted from the rest mass. For the consistent treatment of energies as sources of curvature in the Einstein field equations, this study includes these subtracted self-energies into vacuum energy expressed by the constant Lambda (used in such as Lambda-CDM). In this study, the self-energies in electrodynamics and macroscopic classical Einstein field equations are examined, using the formalisms with the ultraviolet cut-off scheme. One of the cut-off formalisms is the field theory in terms of the step-function-type basis functions, developed by the present authors. The other is a continuum theory of a fundamental particle with the same cut-off length. Based on the effectiveness of the continuum theory with the cut-off length shown in the examination, the dominant self-energy is the quadratic term of the Higgs field at a quantum level (classical self-energies are reduced to logarithmic forms by quantum corrections). The cut-off length is then determined to reproduce today's tiny value of Lambda for vacuum energy. Additionally, a field with nonperiodic vanishing boundary conditions is treated, showing that the field has no zero-point energy.

  14. Visual pigments of marine carnivores: pinnipeds, polar bear, and sea otter.

    PubMed

    Levenson, David H; Ponganis, Paul J; Crognale, Michael A; Deegan, Jess F; Dizon, Andy; Jacobs, Gerald H

    2006-08-01

    Rod and cone visual pigments of 11 marine carnivores were evaluated. Rod, middle/long-wavelength sensitive (M/L) cone, and short-wavelength sensitive (S) cone opsin (if present) sequences were obtained from retinal mRNA. Spectral sensitivity was inferred through evaluation of known spectral tuning residues. The rod pigments of all but one of the pinnipeds were similar to those of the sea otter, polar bear, and most other terrestrial carnivores with spectral peak sensitivities (lambda(max)) of 499 or 501 nm. Similarly, the M/L cone pigments of the pinnipeds, polar bear, and otter had inferred lambda(max) of 545 to 560 nm. Only the rod opsin sequence of the elephant seal had sensitivity characteristic of adaptation for vision in the marine environment, with an inferred lambda(max) of 487 nm. No evidence of S cones was found for any of the pinnipeds. The polar bear and otter had S cones with inferred lambda(max) of approximately 440 nm. Flicker-photometric ERG was additionally used to examine the in situ sensitivities of three species of pinniped. Despite the use of conditions previously shown to evoke cone responses in other mammals, no cone responses could be elicited from any of these pinnipeds. Rod photoreceptor responses for all three species were as predicted by the genetic data.

  15. Efficacy of alpha-cypermethrin and lambda-cyhalothrin applications to prevent Aedes breeding in tires.

    PubMed

    Pettit, William J; Whelan, Peter I; McDonnell, Joseph; Jacups, Susan P

    2010-12-01

    The efficacy of alpha-cypermethrin (Cyperthor) and lambda-cyhalothrin (Demand) to prevent mosquito larval colonization of water-containing receptacles was investigated using 2 differing applications in disused car tires in Darwin, Australia. Insecticide treatments were applied uniformly to the inside surfaces of 2 categories of tires: 1) dry tires that were partially filled with water 24 h after spraying and 2) wet tires partially filled with water prior to spraying. All mosquito larvae, pupae, and dead adults were collected from the treatment and control tires weekly over the 24-wk study period and were later identified to species in the laboratory. Control tires were colonized by Aedes notoscriptus in wk 2 and by Culex quinquefasciatus in wk 4. Aedes notoscriptus failed to colonize any alpha-cypermethrin-treated tires until wk 22 and did not colonize any lambda-cyhalothrin-treated tires during the 24-wk trial. Culex quinquefasciatus colonized alpha-cypermethrin and lambda-cyhalothrin-treated tires from wk 11 and wk 15, respectively. These results indicate both insecticides using either application method can prevent colonization of Ae. notoscriptus for at least 20 wk and demonstrate great potential for the prevention of breeding in receptacles for other receptacle-breeding Aedes species, such as the dengue vectors, Ae. aegypti and Ae. albopictus.

  16. Analysis of wavelet-filtered tonic-clonic electroencephalogram recordings.

    PubMed

    Rosso, O A; Figliola, A; Creso, J; Serrano, E

    2004-07-01

    EEG signals obtained during tonic-clonic epileptic seizures can be severely contaminated by muscle and physiological noise. Heavily contaminated EEG signals are hard to analyse quantitatively and also are usually rejected for visual inspection by physicians, resulting in a considerable loss of collected information. The aim of this work was to develop a computer-based method of time series analysis for such EEGs. A method is presented for filtering those frequencies associated with muscle activity using a wavelet transform. One of the advantages of this method over traditional filtering is that wavelet filtering of some frequency bands does not modify the pattern of the remaining ones. In consequence, the dynamics associated with them do not change. After generation of a 'noise free' signal by removal of the muscle artifacts using wavelets, a dynamic analysis was performed using non-linear dynamics metric tools. The characteristic parameters evaluated (correlation dimension D2 and largest Lyapunov exponent lambda1) were compatible with those obtained in previous works. The average values obtained were: D2=4.25 and lambda1=3.27 for the pre-ictal stage; D2=4.03 and lambda1=2.68 for the tonic seizure stage; D2=4.11 and lambda1=2.46 for the clonic seizure stage.

  17. Pseudo-Bartter syndrome as the sole manifestation of cystic fibrosis in a child with 711+G>T/IVS8-5T mutation: a new face of an old disease.

    PubMed

    Tinsa, Faten; Hadj Fredj, Sondes; Bel Hadj, Imen; Khalsi, Fatma; Abdelhak, Sonia; Boussetta, Khadija; Messaoud, Taieb

    2017-08-01

    Pseudo-Bartter syndrome (PBS) describes an uncommon complication of cystic fibrosis leading to hypochloraemic, hypokalaemic metabolic alkalosis. PBS as the sole manifestation of cystic fibrosis in children is extremely rare and has never been described in patients carrying 5T variant. We report a clinical, biochemical and genetic study of a four year-old boy presenting a pseudo-Bartter syndrome as the sole manifestation of cystic fibrosis. All 27 exons and the flanking intron regions of the CFTR gene were analysed by PCR and direct sequencing. Direct sequencing was also used to analyse TG m T n and M470V polymorphisms in the patient and his parents. Two sweat tests were abnormal with elevated chloride levels at 78 and 88 mmol/L. DNA sequencing revealed a heterozygous mutation 711+1 G>T and an IVS8-T5 allele. The mutation 711+1 G>T is in trans with the IVS8-T5-TG11 allele and the child carried M470/V470 genotype. To the best of our knowledge, the genotype 711+1 G>T /IVS8-5T found in our patient is described for the first time. The role of TG11-5T-V470 allele in cases of cystic fibrosis with PB syndrome remains to be determined.

  18. Analysis of a GRACE global mascon solution for Gulf of Alaska glaciers

    USGS Publications Warehouse

    Arendt, Anthony; Luthcke, Scott; Gardner, Alex; O'Neel, Shad; Hill, David; Moholdt, Geir; Abdalati, Waleed

    2013-01-01

    We present a high-resolution Gravity Recovery and Climate Experiment (GRACE) mascon solution for Gulf of Alaska (GOA) glaciers and compare this with in situ glaciological, climate and other remote-sensing observations. Our GRACE solution yields a GOA glacier mass balance of –65 ± 11 Gt a–1 for the period December 2003 to December 2010, with summer balances driving the interannual variability. Between October/November 2003 and October 2009 we obtain a mass balance of –61 ± 11 Gt a–1 from GRACE, which compares well with –65 ± 12 Gt a–1 from ICESat based on hypsometric extrapolation of glacier elevation changes. We find that mean summer (June–August) air temperatures derived from both ground and lower-troposphere temperature records were good predictors of GRACE-derived summer mass balances, capturing 59% and 72% of the summer balance variability respectively. Large mass losses during 2009 were likely due to low early melt season surface albedos, measured by the Moderate Resolution Imaging Spectroradiometer (MODIS) and likely associated with the 31 March 2009 eruption of Mount Redoubt, southwestern Alaska. GRACE data compared well with in situ measurements at Wolverine Glacier (maritime Alaska), but poorly with those at Gulkana Glacier (interior Alaska). We conclude that, although GOA mass estimates from GRACE are robust over the entire domain, further constraints on subregional and seasonal estimates are necessary to improve fidelity to ground observations.

  19. GORDON, RICHARD F., ASTRONAUT - MISC. - GEMINI-TITAN (GT)-XI - RECOVERY - FROGMEN - ATLANTIC

    NASA Image and Video Library

    1966-09-15

    S66-50759 (15 Sept. 1966) --- Astronaut Richard F. Gordon Jr., pilot of the Gemini-11 spaceflight, is hoisted from the water by a recovery helicopter from the prime recovery ship USS Guam. Gemini-11 splashed down in the western Atlantic recovery area at 9 a.m. (EST), Sept. 15, 1966, to conclude the three-day mission in space. Astronaut Charles Conrad Jr. (out of frame) is the Gemini-11 command pilot. Photo credit: NASA

  20. Genotype analyses of human commensal scalp fungi, Malassezia globosa, and Malassezia restricta on the scalps of patients with dandruff and healthy subjects.

    PubMed

    Hiruma, Midori; Cho, Otomi; Hiruma, Masataro; Kurakado, Sanae; Sugita, Takashi; Ikeda, Shigaku

    2014-06-01

    Dandruff and seborrheic dermatitis are common afflictions of the human scalp caused by commensal scalp fungi belonging to the genus Malassezia. Malassezia globosa and Malassezia restricta are the predominant species found on the scalp. The intergenic spacer regions of these species' rRNA genes contain short sequence repeats (SSR): (GT)n and (CT)n in M. globosa and (CT)n and (AT)n in M. restricta. In the present study, we compared the genotypes (SSR) of M. globosa and M. restricta colonizing the scalps of patients with dandruff and healthy individuals. For M. globosa, the genotype (GT)10:(CT)8 (40.3 %, 25/62) was predominant followed by (GT)9:(CT)8 (14.5 %, 9/62) and (GT)11:(CT)8 (14.5 %, 9/62) in patients with dandruff, whereas the genotypes in healthy subjects were diverse. For M. restricta, the genotype (CT)6:(AT)6 (59.7 %, 37/62) was predominant followed by (CT)6:(AT)8 (24.2 %, 15/62) in patients with dandruff, while four genotypes, (CT)6:(AT)6 (10.5 %, 6/57), (CT)6:(AT)7 (22.8 %, 13/57), (CT)6:(AT)8 (17.5 %, 10/57), and (CT)6:(AT)10 (21.1 %, 12/57), accounted for 71.9 % of all combinations in healthy subjects. The results of this study suggest that the M. globosa genotype (GT)10:(CT)8 and the M. restricta genotype (CT)6:(AT)6 may be involved in the development of dandruff.

  1. Basin mass dynamic changes in China from GRACE based on a multibasin inversion method

    NASA Astrophysics Data System (ADS)

    Yi, Shuang; Wang, Qiuyu; Sun, Wenke

    2016-05-01

    Complex landforms, miscellaneous climates, and enormous populations have influenced various geophysical phenomena in China, which range from water depletion in the underground to retreating glaciers on high mountains and have attracted abundant scientific interest. This paper, which utilizes gravity observations during 2003-2014 from the Gravity Recovery and Climate Experiment (GRACE), intends to comprehensively estimate the mass status in 16 drainage basins in the region. We propose a multibasin inversion method that features resistance to stripe noise and an ability to alleviate signal attenuation from the truncation and smoothing of GRACE data. The results show both positive and negative trends. Tremendous mass accumulation has occurred from the Tibetan Plateau (12.1 ± 0.6 Gt/yr) to the Yangtze River (7.7 ± 1.3 Gt/yr) and southeastern coastal areas, which is suggested to involve an increase in the groundwater storage, lake and reservoir water volume, and the flow of materials from tectonic processes. Additionally, mass loss has occurred in the Huang-Huai-Hai-Liao River Basin (-10.2 ± 0.9 Gt/yr), the Brahmaputra-Nujiang-Lancang River Basin (-15.0 ± 1.1 Gt/yr), and Tienshan Mountain (-4.1 ± 0.3 Gt/yr), a result of groundwater pumping and glacier melting. Areas with groundwater depletion are consistent with the distribution of cities with land subsidence in North China. We find that intensified precipitation can alter the local water supply and that GRACE can adequately capture these dynamics, which could be instructive for China's South-to-North Water Diversion hydrologic project.

  2. Ground and surface temperature variability for remote sensing of soil moisture in a heterogeneous landscape

    USGS Publications Warehouse

    Giraldo, M.A.; Bosch, D.; Madden, M.; Usery, L.; Finn, M.

    2009-01-01

    At the Little River Watershed (LRW) heterogeneous landscape near Tifton Georgia US an in situ network of stations operated by the US Department of Agriculture-Agriculture Research Service-Southeast Watershed Research Lab (USDA-ARS-SEWRL) was established in 2003 for the long term study of climatic and soil biophysical processes. To develop an accurate interpolation of the in situ readings that can be used to produce distributed representations of soil moisture (SM) and energy balances at the landscape scale for remote sensing studies, we studied (1) the temporal and spatial variations of ground temperature (GT) and infra red temperature (IRT) within 30 by 30 m plots around selected network stations; (2) the relationship between the readings from the eight 30 by 30 m plots and the point reading of the network stations for the variables SM, GT and IRT; and (3) the spatial and temporal variation of GT and IRT within agriculture landuses: grass, orchard, peanuts, cotton and bare soil in the surrounding landscape. The results showed high correlations between the station readings and the adjacent 30 by 30 m plot average value for SM; high seasonal independent variation in the GT and IRT behavior among the eight 30 by 30 m plots; and site specific, in-field homogeneity in each 30 by 30 m plot. We found statistical differences in the GT and IRT between the different landuses as well as high correlations between GT and IRT regardless of the landuse. Greater standard deviations for IRT than for GT (in the range of 2-4) were found within the 30 by 30 m, suggesting that when a single point reading for this variable is selected for the validation of either remote sensing data or water-energy models, errors may occur. The results confirmed that in this landscape homogeneous 30 by 30 m plots can be used as landscape spatial units for soil moisture and ground temperature studies. Under this landscape conditions small plots can account for local expressions of environmental processes, decreasing the errors and uncertainties in remote sensing estimates caused by landscape heterogeneity.

  3. The genetics of green thorax, a new larval colour mutant, non-linked with ruby - eye locus in the malaria mosquito, Anopheles stephensi.

    PubMed

    Sanil, D; Shetty, N J

    2009-06-01

    Anopheles stephensi, an important vector of malaria continues to be distributed widely in the Indian subcontinent. The natural vigour of the species combined with its new tolerance, indeed resistance to insecticides has made it obligatory that we look for control methods involving genetic manipulation. Hence, there is an immediate need for greater understanding of the genetics of this vector species. One of the requirements for such genetic studies is the establishment of naturally occurring mutants, establishment of the genetic basis for the same and use of such mutants in the genetic transformation studies and other genetic control programme(s). This paper describes the isolation and genetic studies of a larval colour mutant, green thorax (gt), and linkage studies involving another autosomal recessive mutant ruby- eye (ru) in An. stephensi. After the initial discovery, the mutant green thorax was crossed inter se and pure homozygous stock of the mutant was established. The stock of the mutant ruby- eye, which has been maintained as a pure stock in the laboratory. Crosses were made between the wild type and mutant, green thorax to determine the mode of inheritance of green thorax. For linkage studies, crosses were made between the mutant green thorax and another autosomal recessive mutant ruby-eye. The percentage cross-over was calculated for the genes linkage relationship for gt and gt ru. Results of crosses between mutant and wild type showed that the inheritance of green thorax (gt) in An. stephensi is monofactorial in nature. The gt allele is recessive to wild type and is autosomal. The linkage studies showed no linkage between ru and gt. The mutant gt represents an excellent marker for An. stephensi as it is expressed in late III instar stage of larvae and is prominent in IV instar and pupal stages with complete penetrance and high viability. The said mutant could be easily identified without the aid of a microscope. This mutant can be used extensively to conduct basic and applied research. The mutant has been maintained in two large cages in our laboratory.

  4. Mineral equilibria and zircon, garnet and titanite U-Pb ages constraining the PTt path of granite-related hydrothermal systems at the Big Bell gold deposit, Western Australia

    NASA Astrophysics Data System (ADS)

    Mueller, Andreas G.; McNaughton, Neal J.

    2018-01-01

    The Big Bell deposit (75 t gold) is located in a narrow spur of the Meekatharra greenstone belt, Yilgarn Craton, Western Australia. Two ore bodies are located in a calcic-potassic contact alteration zone overprinting lineated granodiorite dykes and amphibolite: almandine-cummingtonite-hornblende skarn (1-3 g/t Au, 1700 g/t As, 330 g/t W) and the muscovite-microcline gneiss (3-5 g/t Au, 580 g/t Sb, 620 g/t W) of the Main Lode. Genetic models vary from pre- to post-metamorphic replacement. Hornblende-plagioclase pairs in amphibolite constrain peak metamorphic temperature to 670 ± 50 °C. In contrast, garnet-biotite thermometry provides estimates of 578 ± 50 and 608 ± 50 °C for garnet-cordierite-biotite schist bordering the skarn and enveloping the Main Lode. Garnet-cordierite and garnet-hornblende pairs extend the range of fluid temperature to 540 ± 65 °C, well below peak metamorphic temperature. At 540-600 °C, the alteration assemblage andalusite + sillimanite constrains pressure to 300-400 MPa corresponding to 11-14 km crustal depth. Published U-Pb ages indicate that metamorphism took place in the aureole of the southeast granodiorite-tonalite batholith (2740-2700 Ma), followed by gold mineralization at 2662 ± 5 Ma and by the emplacement of biotite granite and Sn-Ta-Nb granite-pegmatite dykes at 2625-2610 Ma. Amphibolite xenoliths in granite northwest of the deposit record the lowest temperature (628 ± 50 °C), suggesting it lacks a metamorphic aureole. The rare metal dykes are spatially associated with epidote-albite and andradite-diopside skarns (≤1.5 g/t Au), mined where enriched in the weathered zone. We analysed hydrothermal zircon intergrown with andradite. Concordant U-Pb ages of 2612 ± 7 and 2609 ± 10 Ma confirm the presence of a second granite-related system. The zircons display oscillatory zoning and have low Th/U ratios (0.05-0.08). Low-Th titanite from an albite granite dyke has a concordant but reset U-Pb age of 2577 ± 7 Ma.

  5. Consumption of milk-protein combined with green tea modulates diet-induced thermogenesis.

    PubMed

    Hursel, Rick; Westerterp-Plantenga, Margriet S

    2011-08-01

    Green tea and protein separately are able to increase diet-induced thermogenesis. Although their effects on long-term weight-maintenance were present separately, they were not additive. Therefore, the effect of milk-protein (MP) in combination with green tea on diet-induced thermogenesis (DIT) was examined in 18 subjects (aged 18-60 years; BMI: 23.0 ± 2.1 kg/m(2)). They participated in an experiment with a randomized, 6 arms, crossover design, where energy expenditure and respiratory quotient (RQ) were measured. Green tea (GT)vs. placebo (PL) capsules were either given in combination with water or with breakfasts containing milk protein in two different dosages: 15 g (15 MP) (energy% P/C/F: 15/47/38; 1.7 MJ/500 mL), and 3.5 g (3.5 MP) (energy% P/C/F: 41/59/0; 146.4 kJ/100 mL). After measuring resting energy expenditure (REE) for 30 min, diet-induced energy expenditure was measured for another 3.5 h after the intervention. There was an overall significant difference observed between conditions (p < 0.001). Post-hoc, areas under the curve (AUCs) for diet-induced energy expenditure were significantly different (P ≤ 0.001) for GT + water (41.11 [91.72] kJ·3.5 h) vs. PL + water (10.86 [28.13] kJ·3.5 h), GT + 3.5 MP (10.14 [54.59] kJ·3.5 h) and PL + 3.5 MP (12.03 [34.09] kJ·3.5 h), but not between GT + 3.5 MP, PL + 3.5 MP and PL + water, indicating that MP inhibited DIT following GT. DIT after GT + 15 MP (167.69 [141.56] kJ·3.5 h) and PL + 15 MP (168.99 [186.56] kJ·3.5 h) was significantly increased vs. PL + water (P < 0.001), but these were not different from each other indicating that 15 g MP stimulated DIT, but inhibited the GT effect on DIT. No significant differences in RQ were seen between conditions for baseline and post-treatment. In conclusion, consumption of milk-protein inhibits the effect of green tea on DIT.

  6. Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil.

    PubMed

    Malta, Fernanda; Gaspareto, Karine Vieira; Lisboa-Neto, Gaspar; Carrilho, Flair José; Mendes-Correa, Maria Cássia; Pinho, João Renato Rebello

    2017-11-13

    Non-structural 5A protein (NS5A) resistance-associated substitutions (RASs) have been identified in patients infected with hepatitis C virus (HCV), even prior to exposure to direct-acting antiviral agents (DAAs). Selection for these variants occurs rapidly during treatment and, in some cases, leads to antiviral treatment failure. DAAs are currently the standard of care for hepatitis C treatment in many parts of the world. Nevertheless, in Brazil, the prevalence of pre-existing NS5A RASs is largely unknown. In this study, we evaluated the frequency of naturally occurring NS5A RASs in Brazilian patients infected with HCV as either a monoinfection or coinfection with human immunodeficiency virus (HIV). Direct Sanger sequencing of the NS5A region was performed in 257 DAA-naïve patients chronically infected with HCV (156 monoinfected with HCV and 101 coinfected with HIV/HCV). The frequencies of specific RASs in monoinfected patients were 14.6% for HCV GT-1a (M28 V and Q30H/R), 6.0% for GT-1b (L31F/V and Y93H), and 22.6% for GT-3a (A30K and Y93H). For HIV/HCV-coinfected patients, the frequencies of RAS were 3.9% for GT-1a (M28 T and Q30H/R), and 11.1% for GT-1b (Y93H); no RASs were found in GT-3a sequences. Substitutions that may confer resistance to NS5A inhibitors exist at baseline in Brazilian DAA-naïve patients infected with HCV GT-1a, -1b, and -3a. Standardization of RAS definitions is needed to improve resistance analyses and to facilitate comparisons of substitutions reported across studies worldwide. Therapeutic strategies should be optimized to efficiently prevent DAA treatment failure due to selection for RASs, especially in difficult-to-cure patients.

  7. Population-based comparison of two feeding tube approaches for head and neck cancer patients receiving concurrent systemic-radiation therapy: is a prophylactic feeding tube approach harmful or helpful?

    PubMed

    Olson, Robert; Karam, Irene; Wilson, Gavin; Bowman, Angela; Lee, Christopher; Wong, Frances

    2013-12-01

    The purpose of this study is to compare patient outcomes between a therapeutic versus a prophylactic gastrostomy tube (GT) placement approach in patients treated with concurrent systemic and radiation (SRT) therapy for head and neck cancer (HNC). Outcomes were compared between all HNC patients treated with concurrent SRT from January 2001 to June 2009 from a center that only places GTs therapeutically when clinically necessary (center A) versus a center that generally places them prophylactically (center B). A total of 445 patients with HNC were identified, with 63 % from center A. As anticipated, GTs were placed less commonly in center A compared to B (31 versus 88 %; p < 0.001). Center B had a significantly higher number of GT complications (p < 0.001), including infection (16 versus 5 %), leakage (10 versus 2 %), and blockage (3 versus 1 %). Conversely, center A had a higher admission rate (27 versus 13 %, p = 0.001), most prominent for GT-related issues (15 versus 6 %). Center B had higher GT dependence at 90 days post-radiation therapy (34 versus 12 %; p < 0.001), but not at 1 year (11 versus 10 %; p = 0.74). There was no significant difference in the proportion of head and neck patients who had a 10 % weight loss at 1 year (compared to baseline) between centers A and B (42 versus 53 %, p = 0.07). There was no significant difference in the overall survival (A versus B, HR = 0.99; p = 0.96). A prophylactic GT approach results in exposing higher number of patients to GT complications. The higher rate of hospitalizations using a therapeutic approach suggests that patients are sicker when GTs are required. Given the similar weight loss and survival, a therapeutic approach at an earlier stage of need may be a preferable approach, when access to prompt GT placement is available.

  8. Stable High-Performance Perovskite Solar Cells Based on Inorganic Electron Transporting Bi-layers.

    PubMed

    Gu, Hao; Zhao, Chen; Zhang, Yiqiang; Shao, Guosheng

    2018-06-27

    As one of the significant electron transporting materials (ETM) in efficient planar heterojunction perovskite solar cells (PSCs), SnO<sub>2</sub> can collect/transfer photo-generated carriers produced in perovskite active absorbers and suppress the carrier recombination at interfaces. In this study, we demonstrate that mild solution-processed SnO<sub>2</sub> compact layer can be an eminent ETM for planar heterojunction PSCs. Here, the device based on chemical-bath-deposited SnO<sub>2</sub> electron transporting layer (ETL) exhibits a power conversion efficiency (PCE) of 16.10% and with obvious hysteresis effect (hysteresis index=19.5%), owing to the accumulation and recombination of charge carriers at SnO<sub>2</sub>/perovskite interface. In order to improve the carrier dissociation and transport process, an ultrathin TiO<sub>2</sub> film was deposited on the top of SnO<sub>2</sub> ETL passivating nonradiative recombination center. The corresponding device based on TiO<sub>2</sub>@SnO<sub>2</sub> electron transporting bi-layer (ETBL) exhibited a high PCE (17.45%) and a negligible hysteresis effect (hysteresis index=1.5%). These findings indicate that this facile solution-processed TiO<sub>2</sub>@SnO<sub>2</sub> ETBL paves a scalable and inexpensive way for fabricating hysteresis-less and high-performance PSCs. © 2018 IOP Publishing Ltd.

  9. Energy of the ground and 2{sup +} excited states of {sub {lambda}}{sub {lambda}}{sup 10}Be: A partial ten-body model

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

    Shoeb, Mohammad; Sonika

    2009-08-15

    The energies of the ground and excited 2{sup +} states of {sub {lambda}}{sub {lambda}}{sup 10}Be have been calculated variationally in the Monte Carlo framework. The hypernucleus is treated as a partial ten-body problem in the {lambda}{lambda}+{alpha}{alpha} model where nucleonic degrees of freedom of {alpha}'s are taken into consideration ignoring the antisymmetrization between two {alpha}'s. The central two-body {lambda}N and {lambda}{lambda} and the three-body dispersive and two-pion exchange {lambda}NN forces, constrained by the {lambda}p scattering data and the observed ground state energies of {sub {lambda}}{sup 5}He and {sub {lambda}}{sub {lambda}}{sup 6}He, are employed. The product-type trial wave function predicts binding energymore » for the ground state considerably less than for the event reported by Danysz et al.; however, it is consistent with the value deduced assuming a {gamma} ray of 3.04 MeV must have escaped undetected in the decay of the product {sub {lambda}}{sup 9}Be* {yields} {sub {lambda}}{sup 9}Be+{gamma} of the emulsion event {sub {lambda}}{sub {lambda}}{sup 10}Be{yields} {pi}{sup -}+p+{sub {lambda}}{sup 9}Be* and for the excited 2{sup +} state closer to the value measured in the Demachi-Yanagi event. The hypernucleus {sub {lambda}}{sub {lambda}}{sup 10}Be has an oblate shape in the excited state. These results are consistent with the earlier four-body {alpha} cluster model approach where {alpha}'s are assumed to be structureless entities.« less

  10. Effects of vaccine-acquired polyclonal anti-HBs antibodies on the prevention of HBV infection of non-vaccine genotypes.

    PubMed

    Kato, Masaki; Hamada-Tsutsumi, Susumu; Okuse, Chiaki; Sakai, Aiko; Matsumoto, Nobuyuki; Sato, Masaaki; Sato, Toshiyuki; Arito, Mitsumi; Omoteyama, Kazuki; Suematsu, Naoya; Okamoto, Kazuki; Kato, Takanobu; Itoh, Fumio; Sumazaki, Ryo; Tanaka, Yasuhito; Yotsuyanagi, Hiroshi; Kato, Tomohiro; Kurokawa, Manae Suzuki

    2017-09-01

    In universal hepatitis B (HB) vaccination, single vaccine-derived polyclonal anti-HBs antibodies (anti-HBs) need to inhibit infection of HB viruses (HBV) of non-vaccine genotypes. We experimentally addressed this issue. Anti-HBs-positive sera were obtained by vaccination with genotype A- or C-derived HBs antigen (HBsAg, gtA-sera or gtC-sera). Their reactivity to genotype A- and C-derived HBsAg (gtA-Ag and gtC-Ag) was measured by ELISA. The capacity of sera to neutralize HBV was evaluated using an in vitro infection model. Of 135 anti-gtA-Ag-reactive gtA-sera, 134 (99.3%) were anti-gtC-Ag-reactive. All (100%) 120 anti-gtC-Ag-reactive gtC-sera were anti-gtA-Ag-reactive. The reactivity to gtA-Ag was strongly correlated with that to gtC-Ag (gtA-sera, ρ = 0.989; gtC-sera, ρ = 0.953; p < 0.01). In gtA-sera (n = 10), anti-HBs to gtA-Ag were less completely absorbed with gtC-Ag (96.4%) than with gtA-Ag (100%, p < 0.05). Similarly, in gtC-sera (n = 10), anti-HBs to gtC-Ag were less completely absorbed with gtA-Ag (96.0%) than with gtC-Ag (100%, p < 0.01). Thus, 3.6 and 4.0% of anti-HBs in gtA-sera and gtC-sera were vaccine genotype HBsAg-specific, respectively. In the neutralization test, gtA-sera (n = 4) and gtC-sera (n = 3) with anti-HBs titers adjusted to 100 mIU/mL equally inhibited genotype C HBV infection (92.8 vs. 95.4%, p = 0.44). However, at 30 mIU/mL, the gtA-sera less effectively inhibited infection than the gtC-sera (60.2 vs. 90.2%, p < 0.05). Vaccination with genotype A- or C-derived HBsAg provided polyclonal anti-HBs that sufficiently bound to non-vaccine genotype HBsAg. However, a small portion of anti-HBs were specific to the vaccine genotype HBsAg. High anti-HBs titers would be required to prevent HBV infection of non-vaccine genotypes. UMIN/CTR UMIN000014363.

  11. Observations and Parameterizations of Particle Size Distributions in Deep Tropical Cirrus and Stratiform Precipitation Clouds: Results from In-Situ Observations in TRMM Field Campaigns

    NASA Technical Reports Server (NTRS)

    Heymsfield, Andrew J.; Bansemer, Aaron; Field, Paul R.; Durden, Stephen L.; Stith, Jeffrey L.; Dye, James E.; Hall, William; Grainger, Cedric A.

    2002-01-01

    In this study, we report on the evolution of particle size distributions (PSDs) and habits as measured during slow, Lagrangian-type spiral descents through deep subtropical and tropical cloud layers in Florida, Brazil, and Kwajalein, Marshall Islands, most of which were precipitating. The objective of the flight patterns was to learn more about how the PSDs evolved in the vertical and to obtain information of the vertical structure of microphysical properties. New instrumentation yielding better information on the concentrations of particles in the size (D) range between 0.2 and 2 cm, as well as improved particle imagery, produced more comprehensive observations for tropical stratiform precipitation regions and anvils than have been available previously. Collocated radar observations provided additional information on the vertical structure of the cloud layers sampled. Most of the spirals began at cloud top, with temperatures (T) as low as -50 C, and ended at cloud base or below the melting layer (ML). The PSDs broadened from cloud top towards cloud base, with the largest particles increasing in size from several millimeters at cloud top to one centimeter or larger towards cloud base. Some continued growth was noted in the upper part of the ML. Concentrations of particles less than 1 mm in size decreased with decreasing height. The result was a consistent change in the PSDs in the vertical. Similarly, systematic changes in the size dependence of the particle cross-sectional area was noted with decreasing height. Aggregation-as ascertained from both the changes in the PSDs and evolution of particle habits as observed in high detail with the cloud particle imager (CPI) probe-was responsible for these trends. The PSDs were generally well-represented by gamma distributions of the form N = N0 gamma D microns e- lambda gamma D that were fitted to the PSDs over 1-km horizontal intervals throughout the spirals. The intercept (N0 gamma), slope (lambda gamma), and dispersion (microns) values were derived for each PSD. Exponential curves (N = N0e- lambdaD; micron = 0) were also fitted to the distributions. The lambda gamma values for given spirals varied systematically with temperature as did the values of lambda (exponential), and the data generally conformed to values found in previous studies involving exponential fits to size distributions in mid-latitude frontal and cirrus layers. Considerable variability often noted in the PSD properties during the loops of individual spirals was manifested primarily in large changes in N0 gamma and N0, but micron, lambda gamma and lambda remained fairly stable. Temperature is not found to be the sole factor controlling lambda gamma or lambda but is a primary one. Direct relationships were found between lambda gamma and N0 gamma or lambda gamma and micron for the gamma distributions and lambda and N0 for the exponential. The latter relationship was not found as distinctly in earlier studies; observed PSDs in this study had better fidelity with less scatter. The micron values changed monotonically with T over the range of temperatures and were directly related to N0 gamma or lambda gamma, thereby reducing the number of variables in the PSD functional equation to two. In the upper part of the ML, N0 and lambda continued to decrease, and in the lower part these values began to increase as the largest particles melted. We developed general expressions relating various bulk microphysical, radar, and radiative transfer-related variables to N0 gamma and lambda gamma, useful for both tropical and mid-latitude clouds. These relationships facilitate the specification of a number of bulk properties in cloud and climate models. The results presented in this paper apply best to temperatures between 0 and -40 C, for which the measured radar reflectivities fall in the range of 0 to 25 dBZe.

  12. Beauty Baryons at CDF and DO

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

    Kryemadhi, Abaz

    The results from Tevatron in the baryonic sector are presented. The lifetime of {lambda}b {yields} J/{psi}{lambda}, the observation of hadronic decay of {lambda}b {yields} {lambda}c{pi}, the semileptonic decays of {lambda}b {yields} {lambda}c{mu}{nu}, the hadronization of the b-baryons, and the {lambda}b decays to {lambda}b {yields} p{pi} and {lambda}b {yields} pK are discussed. These measurements paint a nice picture of our understanding of the beauty baryons.

  13. Improved measurement of the form factors in the decay lambda+c-->lambda + nue.

    PubMed

    Hinson, J W; Huang, G S; Lee, J; Miller, D H; Pavlunin, V; Rangarajan, R; Sanghi, B; Shibata, E I; Shipsey, I P J; Cronin-Hennessy, D; Park, C S; Park, W; Thayer, J B; Thorndike, E H; Coan, T E; Gao, Y S; Liu, F; Stroynowski, R; Artuso, M; Boulahouache, C; Blusk, S; Dambasuren, E; Dorjkhaidav, O; Mountain, R; Muramatsu, H; Nandakumar, R; Skwarnicki, T; Stone, S; Wang, J C; Csorna, S E; Danko, I; Bonvicini, G; Cinabro, D; Dubrovin, M; McGee, S; Bornheim, A; Lipeles, E; Pappas, S P; Shapiro, A; Sun, W M; Weinstein, A J; Briere, R A; Chen, G P; Ferguson, T; Tatishvili, G; Vogel, H; Watkins, M E; Adam, N E; Alexander, J P; Berkelman, K; Boisvert, V; Cassel, D G; Duboscq, J E; Ecklund, K M; Ehrlich, R; Galik, R S; Gibbons, L; Gittelman, B; Gray, S W; Hartill, D L; Heltsley, B K; Hsu, L; Jones, C D; Kandaswamy, J; Kreinick, D L; Magerkurth, A; Mahlke-Krüger, H; Meyer, T O; Mistry, N B; Patterson, J R; Peterson, D; Pivarski, J; Richichi, S J; Riley, D; Sadoff, A J; Schwarthoff, H; Shepherd, M R; Thayer, J G; Urner, D; Wilksen, T; Warburton, A; Weinberger, M; Athar, S B; Avery, P; Breva-Newell, L; Potlia, V; Stoeck, H; Yelton, J; Benslama, K; Cawlfield, C; Eisenstein, B I; Gollin, G D; Karliner, I; Lowrey, N; Plager, C; Sedlack, C; Selen, M; Thaler, J J; Williams, J; Edwards, K W; Besson, D; Anderson, S; Frolov, V V; Gong, D T; Kubota, Y; Li, S Z; Poling, R; Smith, A; Stepaniak, C J; Urheim, J; Metreveli, Z; Seth, K K; Tomaradze, A; Zweber, P; Ahmed, S; Alam, M S; Ernst, J; Jian, L; Saleem, M; Wappler, F; Arms, K; Eckhart, E; Gan, K K; Gwon, C; Honscheid, K; Kagan, H; Kass, R; Pedlar, T K; von Toerne, E; Severini, H; Skubic, P; Dytman, S A; Mueller, J A; Nam, S; Savinov, V

    2005-05-20

    Using the CLEO detector at the Cornell Electron Storage Ring, we have studied the distribution of kinematic variables in the decay lambda(+)(c)lambda--> e(+)nu(e). By performing a four-dimensional maximum likelihood fit, we determine the form factor ratio, R= f(2)/f(1) = -0.31 +/- 0.05(stat) +/- 0.04(syst), the pole mass, M(pole) = [2.21 +/- 0.08(stat) +/- 0.14(syst)] GeV/c(2), and the decay asymmetry parameter of the lambda(+)(c), alpha (lambda(c)) = -0.86 +/-0.03(stat) +/- 0.02(syst), for q(2) = 0.67 (GeV/c(2))(2). We compare the angular distributions of the lambda(+)(c) and lambda(-)(c) and find no evidence for CP violation: A(lambda(c)) = (alpha(lambda(c)) + alpha (lambda(c)))/(alpha(lambda(c))-alpha(lambda(c))) = 0.00 +/- 0.03(stat) +/- 0.01(syst) +/- 0.02, where the third error is from the uncertainty in the world average of the CP-violating parameter, A(lambda), for ppi(-).

  14. Twenty-Five Years of Gene Therapy for ADA-SCID: From Bubble Babies to an Approved Drug.

    PubMed

    Ferrua, Francesca; Aiuti, Alessandro

    2017-11-01

    Twenty-five years have passed since first attempts of gene therapy (GT) in children affected by severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) defect, also known by the general public as bubble babies. ADA-SCID is fatal early in life if untreated. Unconditioned hematopoietic stem cell (HSC) transplant from matched sibling donor represents a curative treatment but is available for few patients. Enzyme replacement therapy can be life-saving, but its chronic use has many drawbacks. This review summarizes the history of ADA-SCID GT over the last 25 years, starting from first pioneering studies in the early 1990s using gamma-retroviral vectors, based on multiple infusions of genetically corrected autologous peripheral blood lymphocytes. HSC represented the ideal target for gene correction to guarantee production of engineered multi-lineage progeny, but it required a decade to achieve therapeutic benefit with this approach. Introduction of low-intensity conditioning represented a crucial step in achieving stable gene-corrected HSC engraftment and therapeutic levels of ADA-expressing cells. Recent clinical trials demonstrated that gamma-retroviral GT for ADA-SCID has a favorable safety profile and is effective in restoring normal purine metabolism and immune functions in patients >13 years after treatment. No abnormal clonal proliferation or leukemia development have been observed in >40 patients treated experimentally in five different centers worldwide. In 2016, the medicinal product Strimvelis™ received marketing approval in Europe for patients affected by ADA-SCID without a suitable human leukocyte antigen-matched related donor. Positive safety and efficacy results have been obtained in GT clinical trials using lentiviral vectors encoding ADA. The results obtained in last 25 years in ADA-SCID GT development fundamentally contributed to improve patients' prognosis, together with earlier diagnosis thanks to newborn screening. These advances open the way to further clinical development of GT as treatment for broader applications, from inherited diseases to cancer.

  15. Effect of suppression of arabinoxylan synthetic genes in wheat endosperm on chain length of arabinoxylan and extract viscosity.

    PubMed

    Freeman, Jackie; Lovegrove, Alison; Wilkinson, Mark David; Saulnier, Luc; Shewry, Peter Robert; Mitchell, Rowan Andrew Craig

    2016-01-01

    Arabinoxylan (AX) is the dominant component within wheat (Triticum aestivum L.) endosperm cell walls, accounting for 70% of the polysaccharide. The viscosity of aqueous extracts from wheat grain is a key trait influencing the processing for various end uses, and this is largely determined by the properties of endosperm AX. We have previously shown dramatic effects on endosperm AX in transgenic wheat by down-regulating either TaGT43_2 or TaGT47_2 genes (orthologues to IRX9 and IRX10 in Arabidopsis, respectively) implicated in AX chain extension and the TaXAT1 gene responsible for monosubstitution by 3-linked arabinose. Here, we use these transgenic lines to investigate the relationship between amounts of AX in soluble and insoluble fractions, the chain-length distribution of these measured by intrinsic viscosity and the overall effect on extract viscosity. In transgenic lines expressing either the TaGT43_2 or TaGT47_2 RNAi transgenes, the intrinsic viscosities of water-extractable (WE-AX) and of a water-insoluble alkaline-extracted fraction (AE-AX) were decreased by between 10% and 50% compared to control lines. In TaXAT1 RNAi lines, there was a 15% decrease in intrinsic viscosity of WE-AX but no consistent effect on that of AE-AX. All transgenic lines showed decreases in extract viscosity with larger effects in TaGT43_2 and TaGT47_2 RNAi lines (by up to sixfold) than in TaXAT1 RNAi lines (by twofold). These effects were explained by the decreases in amount and chain length of WE-AX, with decreases in amount having the greater influence. Extract viscosity from wheat grain can therefore be greatly decreased by suppression of single gene targets. © 2015 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  16. GEMINI-TITAN (GT)-12 - EARTH SKY - AGENA RENDEZVOUS - OUTER SPACE

    NASA Image and Video Library

    1966-11-11

    S66-62755 (11 Nov. 1966) --- Excellent stereo and side view of the Agena Target Docking Vehicle as seen from the Gemini-12 spacecraft during rendezvous and docking mission in space. The two spacecraft are 50 feet apart. Photo credit: NASA

  17. 46 CFR 11.315 - Requirements to qualify for an STCW endorsement as master of vessels of less than 500 GT...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... to 50 percent of the total required service. Experience gained in the engine department may be... areas: (i) Search and rescue. (ii) Management of medical care. (iii) Leadership and managerial skills...

  18. Studies on the genetic linkage of bilirubin and androsterone UDP-glucuronyltransferases by cross-breeding of two mutant rat strains.

    PubMed Central

    Nagai, F; Homma, H; Tanase, H; Matsui, M

    1988-01-01

    Gunn rats, which have defects in bilirubin and 4-nitrophenol UDP-glucuronyltransferases (GT), were crossed with LA Wistar rats with a defect in androsterone GT. The F1 hybrids showed normal GT activities towards androsterone, bilirubin and 4-nitrophenol, demonstrating that Gunn and LA ('low activity') Wistar rats inherit a homozygous dominant trait for androsterone GT and bilirubin GT respectively. The F2 progeny showed four different combinations of bilirubin and androsterone GT activities: defects in both GT activities, a single defect in bilirubin GT activity, a single defect in androsterone GT activity and two normal GT activities. They were segregated in the approximate ratio of 1:3:3:9, which is compatible with Mendel's Principle of Independent Assortment. These results provide evidence that androsterone GT and bilirubin GT are located on different chromosomes. In the F2 generation, defective bilirubin and 4-nitrophenol GT activities were not segregated, indicating that these two mutant genes are closely linked on the same chromosome. PMID:3138978

  19. Observation of B{sup 0}{yields}{lambda}{lambda}K{sup 0} and B{sup 0}{yields}{lambda}{lambda}K*{sup 0} at Belle

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

    Chang, Y.-W.; Wang, M.-Z.; Chao, Y.

    2009-03-01

    We study the charmless decays B{yields}{lambda}{lambda}h, where h stands for {pi}{sup +}, K{sup +}, K{sup 0},K*{sup +}, or K*{sup 0}, using a 605 fb{sup -1} data sample collected at the {upsilon}(4S) resonance with the Belle detector at the KEKB asymmetric energy e{sup +}e{sup -} collider. We observe B{sup 0}{yields}{lambda}{lambda}K{sup 0} and B{sup 0}{yields}{lambda}{lambda}K*{sup 0} with branching fractions of (4.76{sub -0.68}{sup +0.84}(stat){+-}0.61(syst))x10{sup -6} and (2.46{sub -0.72}{sup +0.87}{+-}0.34)x10{sup -6}, respectively. The significances of these signals in the threshold-mass enhanced mass region, M{sub {lambda}}{sub {lambda}}<2.85 GeV/c{sup 2}, are 12.4{sigma} and 9.3{sigma}, respectively. We also update the branching fraction B(B{sup +}{yields}{lambda}{lambda}K{sup +})=(3.38{sub -0.36}{sup +0.41}{+-}0.41)x10{supmore » -6} with better accuracy, and report the following measurement or 90% confidence level upper limit in the threshold-mass-enhanced region: B(B{sup +}{yields}{lambda}{lambda}K*{sup +})=(2.19{sub -0.88}{sup +1.13}{+-}0.33)x10{sup -6} with 3.7{sigma} significance; B(B{sup +}{yields}{lambda}{lambda}{pi}{sup +})<0.94x10{sup -6}. A related search for B{sup 0}{yields}{lambda}{lambda}D{sup 0} yields a branching fraction B(B{sup 0}{yields}{lambda}{lambda}D{sup 0})=(1.05{sub -0.44}{sup +0.57}{+-}0.14)x10{sup -5}. This may be compared with the large, {approx}10{sup -4}, branching fraction observed for B{sup 0}{yields}ppD{sup 0}. The M{sub {lambda}}{sub {lambda}} enhancements near threshold and related angular distributions for the observed modes are also reported.« less

  20. Effects of triclosan on hormones and reproductive axis in female Yellow River carp (Cyprinus carpio): Potential mechanisms underlying estrogen effect.

    PubMed

    Wang, Fan; Guo, Xiangmeng; Chen, Wanguang; Sun, Yaowen; Fan, Chaojie

    2017-12-01

    Triclosan (TCS), a member of the class of compounds called pharmaceutical and personal care products (PPCPs), is a broad antibacterial and antifungal agent found in a lot of consumer products. However, TCS hormone effect mechanism in teleost female fish is not clear. Female Yellow River carp (Cyprinus carpio) were exposed to 1/20, 1/10 and 1/5 LC 50 TCS (96h LC 50 of TCS to carp) under semi-static conditions for 42days. Vitellogenin (Vtg), 17β-estradiol (E 2 ), testosterone(T), estrogen receptor (Er), gonadotropin (GtH), and gonadotropin-releasing hormone (GnRH) levels were measured by enzyme-linked immunosorbent assay (ELISA). Meanwhile, we also examined the mRNA expressions of aromatase, GtHs-β, GnRH, and Er by quantitative real-time PCR (qRT-PCR). The results indicated that 1/5 LC 50 TCS induced Vtg in hepatopancreas of female carps by interference with the hypothalamic-pituitary-gonadal (HPG) axis at multiple potential loci through three mechanisms: (a) TCS exposure enhanced the mRNA expression of hypothalamus and gonadal aromatase which converts androgens into estrogens, subsequently increasing serum concentrations of E 2 to induce Vtg in hepatopancreas; (b) TCS treatment increased GnRH and GtH-β mRNA expression and secretion, causing the disturbance of reproductive endocrine and the increase of E 2 to induce Vtg in hepatopancreas; (c) TCS exposure enhanced synthesis and secretion of Er, then it bound to Er to active Vtg synthesis. These mechanisms showed that TCS may induce Vtg production in female Yellow River carp by Er-mediated and non-Er-mediated pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Effects of triclosan (TCS) on hormonal balance and genes of hypothalamus-pituitary- gonad axis of juvenile male Yellow River carp (Cyprinus carpio).

    PubMed

    Wang, Fan; Liu, Fei; Chen, Wanguang; Xu, Ruijie; Wang, Wei

    2018-02-01

    Triclosan (TCS) is a broad spectrum antimicrobial agent which has been widely dispersed and determinated in the aquatic environment. However, the effects of TCS on reproductive endocrine in male fish are poorly understood. In this study, male Yellow River carp (Cyprinus carpio) were exposed to 0, 1/5, 1/10 and 1/20 LC 50 (96 h LC 50 of TCS to carp) TCS under semi-static conditions for 42 d. Vitellogenin (Vtg), 17β-estradiol (E 2 ), testosterone(T), gonadotropin (GtH), and gonadotropin-releasing hormone (GnRH) levels were measured by enzyme-linked immunosorbent assay (ELISA). Meanwhile, we also examined the mRNA expressions of aromatase, GtHs-β, GnRH, estrogen receptor (Er), and androgen receptor (Ar) by quantitative Real-time Polymerase Chain Reaction (qRT-PCR). TCS induced Vtg levels of hepatopancreas, E 2 levels of serum, and inhibited Ar and Er mRNA levels, suggesting that the induction of Vtg production by TCS was indirectly caused by non-Er pathways. TCS-induced Vtg levels by interfering with the reproductive axis at plenty of latent loci of male carps: (a) TCS exposure increased the aromatase mRNA expression of hypothalamus and gonad aromatase, consequently increasing serum concentrations of E 2 to induce Vtg in hepatopancreas; (b) TCS treatment changed GtH-β and GnRH mRNA expression and secretion, causing the disturbance of reproductive endocrine; (c) TCS exposure decreased Ar mRNA levels, indicating potential Ar-mediated antiandrogen action. These mechanisms showed that TCS may induce Vtg production in male carp by non-Er-mediated pathways. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Supramolecular gel electrophoresis of large DNA fragments.

    PubMed

    Tazawa, Shohei; Kobayashi, Kazuhiro; Oyoshi, Takanori; Yamanaka, Masamichi

    2017-10-01

    Pulsed-field gel electrophoresis is a frequent technique used to separate exceptionally large DNA fragments. In a typical continuous field electrophoresis, it is challenging to separate DNA fragments larger than 20 kbp because they migrate at a comparable rate. To overcome this challenge, it is necessary to develop a novel matrix for the electrophoresis. Here, we describe the electrophoresis of large DNA fragments up to 166 kbp using a supramolecular gel matrix and a typical continuous field electrophoresis system. C 3 -symmetric tris-urea self-assembled into a supramolecular hydrogel in tris-boric acid-EDTA buffer, a typical buffer for DNA electrophoresis, and the supramolecular hydrogel was used as a matrix for electrophoresis to separate large DNA fragments. Three types of DNA marker, the λ-Hind III digest (2 to 23 kbp), Lambda DNA-Mono Cut Mix (10 to 49 kbp), and Marker 7 GT (10 to 165 kbp), were analyzed in this study. Large DNA fragments of greater than 100 kbp showed distinct mobility using a typical continuous field electrophoresis system. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Initiation of lambda DNA replication. The Escherichia coli small heat shock proteins, DnaJ and GrpE, increase DnaK's affinity for the lambda P protein.

    PubMed

    Osipiuk, J; Georgopoulos, C; Zylicz, M

    1993-03-05

    It is known that the initiation of bacteriophage lambda replication requires the orderly assembly of the lambda O.lambda P.DnaB helicase protein preprimosomal complex at the ori lambda DNA site. The DnaK, DnaJ, and GrpE heat shock proteins act together to destabilize the lambda P.DnaB complex, thus freeing DnaB and allowing it to unwind lambda DNA near the ori lambda site. The first step of this disassembly reaction is the binding of DnaK to the lambda P protein. In this report, we examined the influence of the DnaJ and GrpE proteins on the stability of the lambda P.DnaK complex. We present evidence for the existence of the following protein-protein complexes: lambda P.DnaK, lambda P.DnaJ, DnaJ.DnaK, DnaK.GrpE, and lambda P.DnaK.GrpE. Our results suggest that the presence of GrpE alone destabilizes the lambda P.DnaK complex, whereas the presence of DnaJ alone stabilizes the lambda P.DnaK complex. Using immunoprecipitation, we show that in the presence of GrpE, DnaK exhibits a higher affinity for the lambda P.DnaJ complex than it does alone. Using cross-linking with glutaraldehyde, we show that oligomeric forms of DnaK exhibit a higher affinity for lambda P than monomeric DnaK. However, in the presence of GrpE, monomeric DnaK can efficiently bind lambda P protein. These findings help explain our previous results, namely that in the GrpE-dependent lambda DNA replication system, the DnaK protein requirement can be reduced up to 10-fold.

  4. Spectroscopic study of the Lambda hypernuclei by the (e,e'K +) reaction

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

    Miyoshi, Toshinobu

    Hypernuclear spectroscopy study via the (e,e'K +) reaction has been carried out for the first time, establishing a new technique to study Lambda hypernuclei. The high quality electron beam at Jefferson Lab made it possible to measure Lambda hypernuclear spectra with an energy resolution better than 1 MeV (FWHM). The present experiment was designed to make full use of the virtual photon flux, which peaks at very forward angles, by detecting scattered electrons at 0 degrees. Scattered positive kaons were also detected near 0 degrees, where the cross section of the kaon photo-production is maximized. This unique kinematical configuration was realized with the HyperNuclear Spectrometer System (HNSS), which consisted of the Short-Orbit Spectrometer, the Enge Split-Pole Spectrometer, and the splitter magnet. Themore » $$12\\atop{Λ}$$B mass spectrum was measured in the 12C(e,e'K +)$$12\\atop{Λ}$$ reaction with 0.9 MeV (FWHM) energy resolution. The averaged binding energy of the $$12\\atop{Λ}$$B ground state doublet was obtained to be 11.7 ± 0.1 (statistical) ± 0.3 (systematic) MeV, which is consistent with emulsion data. The general spectral structure of the 12C(e,e'K +) $$12\\atop{Λ}$$B reaction was found to be similar to that of the 12C(Λ +,K +)$$12\\atop{Λ}$$C reaction, showing characteristic peaks corresponding to sLambda and pLambda orbits, as well as a few core-excited states. The cross section of the $$12\\atop{Λ}$$B ground state doublet was derived to be 117 ± 13 (statistical) ± 14 (systematic) nb/sr. The theoretical prediction of the cross section was consistent with the present result, validating DWIA calculation for hypernuclear yields. The present study proved the effectiveness of the (e,e'K +) reaction for future Lambda hypernuclear spectroscopy studies.« less

  5. Natural protection from zoonosis by alpha-gal epitopes on virus particles in xenotransmission.

    PubMed

    Kim, Na Young; Jung, Woon-Won; Oh, Yu-Kyung; Chun, Taehoon; Park, Hong-Yang; Lee, Hoon-Taek; Han, In-Kwon; Yang, Jai Myung; Kim, Young Bong

    2007-03-01

    Clinical transplantation has become one of the preferred treatments for end-stage organ failure, and one of the novel approaches being pursued to overcome the limited supply of human organs involves the use of organs from other species. The pig appears to be a near ideal animal due to proximity to humans, domestication, and ability to procreate. The presence of Gal-alpha1,3-Gal residues on the surfaces of pig cells is a major immunological obstacle to xenotransplantation. Alpha1,3galactosyltransferase (alpha1,3GT) catalyzes the synthesis of Gal alpha 1-3Gal beta 1-4GlcNAc-R (alpha-gal epitope) on the glycoproteins and glycolipids of non-primate mammals, but this does not occur in humans. Moreover, the alpha-gal epitope causes hyperacute rejection of pig organs in humans, and thus, the elimination of this antigen from pig tissues is highly desirable. Recently, concerns have been raised that the risk of virus transmission from such pigs may be increased due to the absence of alpha-gal on their viral particles. In this study, transgenic cells expressing alpha1,3GT were selected using 1.25 mg/ml neomycin. The development of HeLa cells expressing alpha1,3GT now allows accurate studies to be conducted on the function of the alpha-gal epitope in xenotransmission. The expressions of alpha-gal epitopes on HeLa/alpha-gal cells were demonstrated by flow cytometry and confocal microscopy using cells stained with IB4-fluorescein isothiocyanate lectin. Vaccinia viruses propagated in HeLa/alpha-gal cells also expressed alpha-gal on their viral envelopes and were more sensitive to inactivation by human sera than vaccinia virus propagated in HeLa cells. Moreover, neutralization of vaccinia virus was inhibited in human serum by 10 mm ethylene glycol bis(beta-aminoethylether)tetraacetic acid (EDTA) treatment. Our data indicated that alpha-gal epitopes are one of the major barriers to zoonosis via xenotransmission.

  6. Popularity of Russian information sources of medical education.

    PubMed

    Vasilyeva, Irina V; Arseniev, Sergey B

    2014-01-01

    The aim of the present study is to analyze the popularity of information sources of medical educational sites <webmedinfo.ru>, medical information portal <meduniver.com>, medical portal for students <6years.net>, electronic library of medical literature <booksmed.com>, <medliter.ru> and <medbook.net.ru>. Three sites (<www.webmedinfo.ru>, <meduniver.com> and <6years.net>) provide sources of medical literature, educational videos, medical histories, medical papers and medical popular literature. And three other sites (<www.booksmed.com>, <www.medliter.ru> and <www.medbook.net.ru>) provide sources for electronic medical books on various subjects. Using on-line programs Alexa and Cy-pr we have analyzed the website's rating and identified the main data and time-varying data of the sites. Calculated Alexa Rank rating was determined for each site. Our study has shown that the most popular information sources of medical education among the six studied sites for Russian users is <meduniver.com>; the site <booksmed.com> is at the second place referring to the Alexa Rank rating and the site <webmedinfo.ru> is at the second place referring to the citation index in Yandex. The most popular medical site of electronic medical books is <booksmed.com>.

  7. Chimeric Anti-Human Podoplanin Antibody NZ-12 of Lambda Light Chain Exerts Higher Antibody-Dependent Cellular Cytotoxicity and Complement-Dependent Cytotoxicity Compared with NZ-8 of Kappa Light Chain.

    PubMed

    Kaneko, Mika K; Abe, Shinji; Ogasawara, Satoshi; Fujii, Yuki; Yamada, Shinji; Murata, Takeshi; Uchida, Hiroaki; Tahara, Hideaki; Nishioka, Yasuhiko; Kato, Yukinari

    2017-02-01

    Podoplanin (PDPN), a type I transmembrane 36-kDa glycoprotein, is expressed not only in normal cells, such as renal epithelial cells (podocytes), lymphatic endothelial cells, and pulmonary type I alveolar cells, but also in cancer cells, including brain tumors and lung squamous cell carcinomas. Podoplanin activates platelet aggregation by binding to C-type lectin-like receptor-2 (CLEC-2) on platelets, and the podoplanin/CLEC-2 interaction facilitates blood/lymphatic vessel separation. We previously produced neutralizing anti-human podoplanin monoclonal antibody (mAb), clone NZ-1 (rat IgG 2a , lambda), which neutralizes the podoplanin/CLEC-2 interaction and inhibits platelet aggregation and cancer metastasis. Human-rat chimeric antibody, NZ-8, was previously developed using variable regions of NZ-1 and human constant regions of heavy chain (IgG 1 ) and light chain (kappa chain). Although NZ-8 showed high antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against human podoplanin-expressing cancer cells, the binding affinity of NZ-8 was lower than that of NZ-1. Herein, we produced a novel human-rat chimeric antibody, NZ-12, the constant regions of which consist of IgG 1 heavy chain and lambda light chain. Using flow cytometry, we demonstrated that the binding affinity of NZ-12 was much higher than that of NZ-8. Furthermore, ADCC and CDC activities of NZ-12 were significantly increased against glioblastoma cell lines (LN319 and D397) and lung cancer cell line (PC-10). These results suggested that NZ-12 could become a promising therapeutic antibody against podoplanin-expressing brain tumors and lung cancers.

  8. Physical interactions between bacteriophage and Escherichia coli proteins required for initiation of lambda DNA replication.

    PubMed

    Liberek, K; Osipiuk, J; Zylicz, M; Ang, D; Skorko, J; Georgopoulos, C

    1990-02-25

    The process of initiation of lambda DNA replication requires the assembly of the proper nucleoprotein complex at the origin of replication, ori lambda. The complex is composed of both phage and host-coded proteins. The lambda O initiator protein binds specifically to ori lambda. The lambda P initiator protein binds to both lambda O and the host-coded dnaB helicase, giving rise to an ori lambda DNA.lambda O.lambda P.dnaB structure. The dnaK and dnaJ heat shock proteins have been shown capable of dissociating this complex. The thus freed dnaB helicase unwinds the duplex DNA template at the replication fork. In this report, through cross-linking, size chromatography, and protein affinity chromatography, we document some of the protein-protein interactions occurring at ori lambda. Our results show that the dnaK protein specifically interacts with both lambda O and lambda P, and that the dnaJ protein specifically interacts with the dnaB helicase.

  9. MiR-2964a-5p binding site SNP regulates ATM expression contributing to age-related cataract risk.

    PubMed

    Rong, Han; Gu, Shanshan; Zhang, Guowei; Kang, Lihua; Yang, Mei; Zhang, Junfang; Shen, Xinyue; Guan, Huaijin

    2017-10-17

    This study was to explore the involvement of DNA repair genes in the pathogenesis of age-related cataract (ARC). We genotyped nine single nucleotide polymorphisms (SNPs) of genes responsible to DNA double strand breaks (DSBs) in 804 ARC cases and 804 controls in a cohort of eye diseases in Chinese population and found that the ataxia telangiectasia mutated ( ATM ) gene-rs4585:G>T was significantly associated with ARC risk. An in vitro functional test found that miR-2964a-5p specifically down-regulated luciferase reporter expression and ATM expression in the cell lines transfected with rs4585 T allele compared to rs4585 G allele. The molecular assay on human tissue samples discovered that ATM expression was down-regulated in majority of ARC tissues and correlated with ATM genotypes. In addition, the Comet assay of cellular DNA damage of peripheral lymphocytes indicated that individuals carrying the G allele (GG/GT) of ATM -rs4585 had lower DNA breaks compared to individuals with TT genotype. These findings suggested that the SNP rs4585 in ATM might affect ARC risk through modulating the regulatory affinity of miR-2964a-5p. The reduced DSBs repair might be involved in ARC pathogenesis.

  10. 46 CFR 11.313 - Requirements to qualify for an STCW endorsement as chief mate of vessels of 500 GT or more and...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... of the total required service. Experience gained in the engine department on vessels may be... and managerial skills. (v) Search and rescue. (vi) Management of medical care. (vii) ECDIS, if serving...

  11. 46 CFR 11.311 - Requirements to qualify for an STCW endorsement as master of vessels of 500 GT or more and less...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... to 50 percent of the total required service. Experience gained in the engine department on vessels... meteorology. (iv) Leadership and managerial skills. (v) Search and rescue. (vi) Management of medical care...

  12. 46 CFR 11.305 - Requirements to qualify for an STCW endorsement as master of vessels of 3,000 GT or more...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... gained in the engine department on vessels may be creditable for up to 3 months of the service...) Advanced stability. (iii) Advanced meteorology. (iv) Leadership and managerial skills. (v) Search and...

  13. GEMINI-TITAN (GT)-11 - MISC. - EXPERIMENT D-16 - KNEE TETHER - MSC

    NASA Image and Video Library

    1966-01-28

    S66-00933 (28 Jan. 1966) --- Gemini-11 Experiment D-16 Knee Tether, sponsored by the Department of Defense and the United States Air Force. The astronaut tightens and loosens bolts in a prescribed pattern during his extravehicular activity, once with his body held to the spacecraft by a nine-inch tether looped around his knee and through the handrail, and once without the tether. Photo credit: NASA

  14. GEMINI-TITAN (GT)-11 - EARTH SKY - OUTER SPACE

    NASA Image and Video Library

    1966-09-14

    S66-54706 (14 Sept. 1966) --- Western half of Australia, including the coastline from Perth to Port Darwin, looking west, as seen from the Gemini-11 spacecraft during its 26th revolution of Earth. Photograph was made while the spacecraft was at a record-high apogee of 740 nautical miles. Taken with a modified 70mm Hasselblad camera, using Eastman Kodak, Ektachrome, MS (S.O. 368) color film. Photo credit: NASA

  15. PRELAUNCH - GEMINI-TITAN (GT)-12 - LEAVE TRAILER - CAPE

    NASA Image and Video Library

    1966-11-11

    S66-59916 (11 Nov. 1966) --- Prime crew for the Gemini-12 spaceflight, astronauts James A. Lovell Jr. (leading), command pilot, and Edwin E. Aldrin Jr., pilot, leave the suiting trailer at Launch Complex 16 during prelaunch countdown. Moments later they entered a transport van which carried them to Pad 19 and their waiting spacecraft. The liftoff was at 3:46 p.m. (EST), Nov. 11, 1966. Photo credit: NASA

  16. State-to-state rotationally inelastic scattering of ND[sub 3] on a graphite (0001) surface

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

    LaVilla, M.E.; Ionova, I.V.; Ionov, S.I.

    1992-12-15

    State-selected molecular beams of deuterated ammonia, [vert bar][ital JKM][epsilon][gt][vert bar]inversion[gt]=[vert bar]1111[gt][vert bar][minus][gt] or [vert bar]222[minus]1[gt][vert bar][minus][gt] and [vert bar]3331[gt][vert bar][minus][gt] states in the proportion 2.3:1, are produced via hexapole electrostatic focusing and then scattered at near-normal incidence on a graphite (0001) surface at [ital T][sub [ital s

  17. Pressure-induced structural change in liquid GeI4.

    PubMed

    Fuchizaki, Kazuhiro; Nishimura, Hironori; Hase, Takaki; Saitoh, Hiroyuki

    2017-12-13

    The similarity in the shape of the melting curve of GeI<sub>4</sub> to that of SnI<sub>4</sub> suggests that a liquid-liquid transition as observed in liquid SnI<sub>4</sub> is also expected to occur in liquid GeI<sub>4</sub>. Because the slope of the melting curve of GeI<sub>4</sub> abruptly changes at around 3 GPa, in situ synchrotron diffraction measurements were conducted to examine closely the structural changes upon compression at around 3 GPa. The reduced radial distribution functions of the high- and low-pressure liquid states of GeI<sub>4</sub> share the same feature inherent in the high-pressure (high-density) and low-pressure (low-density) radial distribution functions of liquid SnI<sub>4</sub>. This feature allows us to introduce local order parameters that we may use to observe the transition. Unlike the transition in liquid SnI<sub>4</sub>, the transition from the low-pressure to the high-pressure structure seems sluggish. We speculate that the liquid-liquid critical point of GeI<sub>4</sub> is no longer a thermodynamically stable state and is slightly located below the melting curve. As a result, the structural change is said to be a crossover rather than a transition. The behavior of the local-order parameters implies a metastable extension of the liquid-liquid phase boundary with a negative slope. . © 2017 IOP Publishing Ltd.

  18. A glycosyl transferase family 43 protein involved in xylan biosynthesis is associated with straw digestibility in Brachypodium distachyon.

    PubMed

    Whitehead, Caragh; Ostos Garrido, Francisco J; Reymond, Matthieu; Simister, Rachael; Distelfeld, Assaf; Atienza, Sergio G; Piston, Fernando; Gomez, Leonardo D; McQueen-Mason, Simon J

    2018-05-01

    The recalcitrance of secondary plant cell walls to digestion constrains biomass use for the production of sustainable bioproducts and for animal feed. We screened a population of Brachypodium recombinant inbred lines (RILs) for cell wall digestibility using commercial cellulases and detected a quantitative trait locus (QTL) associated with this trait. Examination of the chromosomal region associated with this QTL revealed a candidate gene that encodes a putative glycosyl transferase family (GT) 43 protein, orthologue of IRX14 in Arabidopsis, and hence predicted to be involved in the biosynthesis of xylan. Arabinoxylans form the major matrix polysaccharides in cell walls of grasses, such as Brachypodium. The parental lines of the RIL population carry alternative nonsynonymous polymorphisms in the BdGT43A gene, which were inherited in the RIL progeny in a manner compatible with a causative role in the variation in straw digestibility. In order to validate the implied role of our candidate gene in affecting straw digestibility, we used RNA interference to lower the expression levels of the BdGT43A gene in Brachypodium. The biomass of the silenced lines showed higher digestibility supporting a causative role of the BdGT43A gene, suggesting that it might form a good target for improving straw digestibility in crops. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

  19. Differences in glycosyltransferase family 61 accompany variation in seed coat mucilage composition in Plantago spp.

    PubMed

    Phan, Jana L; Tucker, Matthew R; Khor, Shi Fang; Shirley, Neil; Lahnstein, Jelle; Beahan, Cherie; Bacic, Antony; Burton, Rachel A

    2016-12-01

    Xylans are the most abundant non-cellulosic polysaccharide found in plant cell walls. A diverse range of xylan structures influence tissue function during growth and development. Despite the abundance of xylans in nature, details of the genes and biochemical pathways controlling their biosynthesis are lacking. In this study we have utilized natural variation within the Plantago genus to examine variation in heteroxylan composition and structure in seed coat mucilage. Compositional assays were combined with analysis of the glycosyltransferase family 61 (GT61) family during seed coat development, with the aim of identifying GT61 sequences participating in xylan backbone substitution. The results reveal natural variation in heteroxylan content and structure, particularly in P. ovata and P. cunninghamii, species which show a similar amount of heteroxylan but different backbone substitution profiles. Analysis of the GT61 family identified specific sequences co-expressed with IRREGULAR XYLEM 10 genes, which encode putative xylan synthases, revealing a close temporal association between xylan synthesis and substitution. Moreover, in P. ovata, several abundant GT61 sequences appear to lack orthologues in P. cunninghamii. Our results indicate that natural variation in Plantago species can be exploited to reveal novel details of seed coat development and polysaccharide biosynthetic pathways. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  20. Cavernous antioxidant effect of green tea, epigallocatechin-3-gallate with/without sildenafil citrate intake in aged diabetic rats.

    PubMed

    Mostafa, T; Sabry, D; Abdelaal, A M; Mostafa, I; Taymour, M

    2013-08-01

    This study aimed to assess the cavernous antioxidant effect of green tea (GT), epigallocatechin-3-gallate (EGCG) with/without sildenafil citrate intake in aged diabetic rats. One hundred and four aged male white albino rat were divided into controls that received ordinary chow, streptozotocin (STZ)-induced aged diabetic rats, STZ-induced diabetic rats on infused green tea, induced diabetic rats on epigallocatechin-3-gallate and STZ-induced diabetic rats on sildenafil citrate added to EGCG. After 8 weeks, dissected cavernous tissues were assessed for gene expression of eNOS, cavernous malondialdehyde (MDA), glutathione peroxidase (GPx), cyclic guanosine monophosphate (cGMP), and serum testosterone (T). STZ-induced diabetic rats on GT demonstrated significant increase in cavernous eNOS, cGMP, GPx and significant decrease in cavernous MDA compared with diabetic rats. Diabetic rats on EGCG demonstrated significant increase in cavernous eNOS, cGMP, GPx and significant decrease in cavernous MDA compared with diabetic rats or diabetic rats on GT. Diabetic rats on EGCG added to sildenafil showed significant increase in cavernous eNOS, cGMP and significant decrease in cavernous MDA compared with other groups. Serum T demonstrated nonsignificant difference between the investigated groups. It is concluded that GT and EGCG have significant cavernous antioxidant effects that are increased if sildenafil is added. © 2012 Blackwell Verlag GmbH.

  1. Permafrost-associated gas hydrate: is it really approximately 1% of the global system?

    USGS Publications Warehouse

    Ruppel, Carolyn

    2015-01-01

    Permafrost-associated gas hydrates are often assumed to contain ∼1 % of the global gas-in-place in gas hydrates based on a study26 published over three decades ago. As knowledge of permafrost-associated gas hydrates has grown, it has become clear that many permafrost-associated gas hydrates are inextricably linked to an associated conventional petroleum system, and that their formation history (trapping of migrated gas in situ during Pleistocene cooling) is consistent with having been sourced at least partially in nearby thermogenic gas deposits. Using modern data sets that constrain the distribution of continuous permafrost onshore5 and subsea permafrost on circum-Arctic Ocean continental shelves offshore and that estimate undiscovered conventional gas within arctic assessment units,16 the done here reveals where permafrost-associated gas hydrates are most likely to occur, concluding that Arctic Alaska and the West Siberian Basin are the best prospects. A conservative estimate is that 20 Gt C (2.7·1013 kg CH4) may be sequestered in permafrost-associated gas hydrates if methane were the only hydrate-former. This value is slightly more than 1 % of modern estimates (corresponding to 1600 Gt C to 1800 Gt C2,22) for global gas-in-place in methane hydrates and about double the absolute estimate (11.2 Gt C) made in 1981.26

  2. Seasonal flux and assemblage composition of planktic foraminifera from the northern Gulf of Mexico, 2008-2012

    USGS Publications Warehouse

    Reynolds, Caitlin E.; Richey, Julie N.; Poore, Richard Z.

    2013-01-01

    The U.S. Geological Survey anchored a sediment trap in the northern Gulf of Mexico beginning in 2008 to collect seasonal time-series data on the flux and assemblage composition of live planktic foraminifers. This report provides an update of the previous time-series data to include results from 2012. Ten species, or varieties, constituted ~92 percent of the 2012 assemblage: Globigerinoides ruber (pink and white varieties), Globigerinoides sacculifer, Globigerina calida, Globigerinella aequilateralis, Globorotalia menardii group [The Gt. menardii group includes Gt. menardii, Gt. tumida, and Gt. ungulata], Orbulina universa, Globorotalia truncatulinoides, Pulleniatina spp., and Neogloboquadrina dutertrei. The mean daily flux was 158 tests per square meter per day (m–2 day–1), with maximum fluxes of >450tests m–2 day–1 during the beginning of July and mid–August and minimum fluxes of –2 day–1 during the beginning of February and mid–July. Globorotalia truncatulinoides showed a clear preference for the winter, consistent with data from 2008 to 2011. Globigerinoides ruber (white) flux data for 2012 (average 23 tests m–2 day–1) were consistent with data from 2011 (average 30 tests m–2 day–1) and 2010 (average 29 tests m–2 day–1) and showed a steady threefold increase since 2009 (average 11 tests m–2 day–1) and a tenfold increase from the 2008 flux (3 tests m–2 day–1).

  3. mRNA expression OF IFN-λs in the gingival tissue of chronic and aggressive periodontitis patients: A polymerase chain reaction study.

    PubMed

    Bilichodmath, Shivaprasad; Nair, Sruthi K; Bilichodmath, Rekha; Mangalekar, Sachin B

    2018-05-01

    Several studies have proven the existence of herpesviruses in periodontal pockets of chronic and aggressive periodontitis patients. Recently discovered interferon lambda (IFN-λ) has antiviral properties and is induced by herpesviruses. The present study was aimed at quantitative analysis of mRNA expression of IFN-λs (IFN-λ1, IFN-λ2, IFN-λ3) in the gingival tissues of chronic and aggressive periodontitis patients. A total of 90 participants (50 males and 40 females; age ranging from 19 to 50 years, mean age 31.50±7.8) were categorized into three groups as healthy participants, chronic periodontitis patients and aggressive periodontitis patients. mRNA expression of IFN-λs in gingival tissues was estimated using reverse transcriptase polymerase chain reaction and was correlated with clinical parameters such as gingival index (GI), probing pocket depth (PPD), and clinical attachment level (CAL). mRNA of IFN-λ1, IFN-λ2 and IFN-λ3 was expressed in gingival tissues of healthy participants, chronic and aggressive periodontitis patients. Highest level of IFN-λ1 was observed in aggressive periodontitis patients (3.049±9.793), whereas IFN-λ2 (4.322±11.310) and IFN-λ3 (11.932±27.479) were maximum in chronic periodontitis patients. The difference in the mRNA expression of IFN-λ1 (p = 0.008) and IFN-λ3 (p = 0.043) among three groups was statistically significant CONCLUSION: Increased quantity of IFN-λs in chronic and aggressive periodontitis patients suggests a role in periodontitis. Variation in the expression of IFN-λ1 and IFN-λ3 in periodontitis patients needs to be further evaluated. The mRNA expression of antiviral IFN-λs in gingival tissues might enhance our understanding related to viral pathogenesis of periodontal diseases. This article is protected by copyright. All rights reserved. © 2018 American Academy of Periodontology.

  4. Magnetotransport study of topological superconductor Cu0.10Bi2Se3 single crystal.

    PubMed

    Li, Mingtao; Fang, Yifei; Zhang, Jincang; Yi, Hemian; Zhou, Xingjiang; Lin, Chengtian

    2018-02-02

    We report a magnetotransport study of vortex-pinning in Cu<sub>0.10</sub>Bi<sub>2</sub>Se<sub>3</sub> single crystal. The sample is demonstrated to be in clean limit and absent of Pauli spin-limiting effect. Interestingly, the resistivity versus magnetic field shows an anomalously pronounced increase when approaching the superconducting-normal state boundary for both B∥ab and B∥c configurations. We have investigated the flux-flowing behavior under various magnetic field and temperatures, enabling us to establish its anisotropic vortex phase diagram. Our results suggest the Cu<sub>0.10</sub>Bi<sub>2</sub>Se<sub>3</sub> can be served as one unique material for exploring exotic surface vortex states in topological superconductors. © 2018 IOP Publishing Ltd.

  5. Effect of tocopherol supplementation during last trimester of pregnancy on mRNA abundances of interleukins and angiogenesis in ovine placenta and uterus.

    PubMed

    Kasimanickam, Ramanathan K; Kasimanickam, Vanmathy R; Haldorson, Gary J; Tibary, Ahmed

    2012-01-23

    Interleukins (IL) play an important role in angiogenesis. Tocopherol possesses immunomodulating effect in addition to antioxidant property. The objective of this study was to determine whether gamma tocopherol's (gT) angiogenic activity in placental network is enhanced via promoting interleukins. Pregnant ewes (N=18) were supplemented, orally, with 500 mg of alpha tocopherol (aT; N=6) or 1,000 mg of gT (N=7) or placebo (CON; N=5) once daily from 107 to 137 days post breeding. Uterine and placental tissue samples were obtained at the end of supplementation to evaluate relative mRNA expressions of IL-1b, IL-6, IL-8, Tumor Necrosis Factor (TNF) alpha, Vascular Endothelial Growth Factor (VEGF), kinase insert domain receptor (KDR; VGFR2; a type III receptor tyrosine kinase), and soluble fms-like tyrosine kniase-1 (sFlt1 or sVEGFR1) in uterus, caruncle and cotyledon. Oral supplementation of gT increased IL-6, IL-8, KDR and VEGF mRNA abundances whereas sFlt1 mRNA abundance was suppressed in uterus, caruncle and cotyledon, compared to aT and placebo treated ewes (P<0.05). The TNF alpha and IL-1b mRNA abundances were suppressed in uterus, caruncle and cotyledon but TNF alpha is higher in gT group compared to aT group (P<0.05), whereas IL-1b was similar between treatment groups (P>0.1). Gamma tocopherol supplementation increased IL-6, IL-8, and KDR mRNA abundances and suppressed sFlt1 and TNFalpha mRNA abundances thereby increased VEGF mRNA expression and angiogenesis in placental vascular network during late gestation. It is plausible that the angiogenic effect of gamma tocopherol in placental vascular network is exerted via an alternate path by enhancing IL-6 and IL-8.

  6. Effect of tocopherol supplementation during last trimester of pregnancy on mRNA abundances of interleukins and angiogenesis in ovine placenta and uterus

    PubMed Central

    2012-01-01

    Background Interleukins (IL) play an important role in angiogenesis. Tocopherol possesses immunomodulating effect in addition to antioxidant property. The objective of this study was to determine whether gamma tocopherol's (gT) angiogenic activity in placental network is enhanced via promoting interleukins. Methods Pregnant ewes (N = 18) were supplemented, orally, with 500 mg of alpha tocopherol (aT; N = 6) or 1,000 mg of gT (N = 7) or placebo (CON; N = 5) once daily from 107 to 137 days post breeding. Uterine and placental tissue samples were obtained at the end of supplementation to evaluate relative mRNA expressions of IL-1b, IL-6, IL-8, Tumor Necrosis Factor (TNF) alpha, Vascular Endothelial Growth Factor (VEGF), kinase insert domain receptor (KDR; VGFR2; a type III receptor tyrosine kinase), and soluble fms-like tyrosine kniase-1 (sFlt1 or sVEGFR1) in uterus, caruncle and cotyledon. Results Oral supplementation of gT increased IL-6, IL-8, KDR and VEGF mRNA abundances whereas sFlt1 mRNA abundance was suppressed in uterus, caruncle and cotyledon, compared to aT and placebo treated ewes (P < 0.05). The TNF alpha and IL-1b mRNA abundances were suppressed in uterus, caruncle and cotyledon but TNF alpha is higher in gT group compared to aT group (P < 0.05), whereas IL-1b was similar between treatment groups (P > 0.1). Conclusions Gamma tocopherol supplementation increased IL-6, IL-8, and KDR mRNA abundances and suppressed sFlt1 and TNFalpha mRNA abundances thereby increased VEGF mRNA expression and angiogenesis in placental vascular network during late gestation. It is plausible that the angiogenic effect of gamma tocopherol in placental vascular network is exerted via an alternate path by enhancing IL-6 and IL-8. PMID:22269218

  7. Colon cancer chemoprevention by a novel NO chimera that shows anti-inflammatory and antiproliferative activity in vitro and in vivo.

    PubMed

    Hagos, Ghenet K; Carroll, Robert E; Kouznetsova, Tatiana; Li, Qian; Toader, Violeta; Fernandez, Patricia A; Swanson, Steven M; Thatcher, Gregory R J

    2007-08-01

    Chemopreventive agents in colorectal cancer possess either antiproliferative or anti-inflammatory actions. Nonsteroidal anti-inflammatory drugs (NSAID) and cyclooxygenase-2 inhibitors have shown promise, but are compromised by side effects. Nitric oxide donor NSAIDs are organic nitrates conjugated via a labile linker to an NSAID, originally designed for use in pain relief, that have shown efficacy in colorectal cancer chemoprevention. The NO chimera, GT-094, is a novel nitrate containing an NSAID and disulfide pharmacophores, a lead compound for the design of agents specifically for colorectal cancer. GT-094 is the first nitrate reported to reduce aberrant crypt foci (by 45%) when administered after carcinogen in the standard azoxymethane rat model of colorectal cancer. Analysis of proximal and distal colon tissue from 8- and 28-week rat/azoxymethane studies showed that GT-094 treatment reduced colon crypt proliferation by 30% to 69%, reduced inducible NO synthase (iNOS) levels by 33% to 67%, reduced poly(ADP-ribose)polymerase-1 expression and cleavage 2- to 4-fold, and elevated levels of p27 in the distal colon 3-fold. Studies in cancer cell cultures recapitulated actions of GT-094: antiproliferative activity and transient G(2)-M phase cell cycle block were measured in Caco-2 cells; apoptotic activity was examined but not observed; anti-inflammatory activity was seen in the inhibition of up-regulation of iNOS and endogenous NO production in lipopolysaccharide (LPS)-induced RAW 264.7 cells. In summary, antiproliferative, anti-inflammatory, and cytoprotective activity observed in vivo and in vitro support GT-094 as a lead compound for the design of NO chimeras for colorectal cancer chemoprevention.

  8. Validation and comparison of two methods to assess human energy expenditure during free-living activities.

    PubMed

    Anastasopoulou, Panagiota; Tubic, Mirnes; Schmidt, Steffen; Neumann, Rainer; Woll, Alexander; Härtel, Sascha

    2014-01-01

    The measurement of activity energy expenditure (AEE) via accelerometry is the most commonly used objective method for assessing human daily physical activity and has gained increasing importance in the medical, sports and psychological science research in recent years. The purpose of this study was to determine which of the following procedures is more accurate to determine the energy cost during the most common everyday life activities; a single regression or an activity based approach. For this we used a device that utilizes single regression models (GT3X, ActiGraph Manufacturing Technology Inc., FL., USA) and a device using activity-dependent calculation models (move II, movisens GmbH, Karlsruhe, Germany). Nineteen adults (11 male, 8 female; 30.4±9.0 years) wore the activity monitors attached to the waist and a portable indirect calorimeter (IC) as reference measure for AEE while performing several typical daily activities. The accuracy of the two devices for estimating AEE was assessed as the mean differences between their output and the reference and evaluated using Bland-Altman analysis. The GT3X overestimated the AEE of walking (GT3X minus reference, 1.26 kcal/min), walking fast (1.72 kcal/min), walking up-/downhill (1.45 kcal/min) and walking upstairs (1.92 kcal/min) and underestimated the AEE of jogging (-1.30 kcal/min) and walking upstairs (-2.46 kcal/min). The errors for move II were smaller than those for GT3X for all activities. The move II overestimated AEE of walking (move II minus reference, 0.21 kcal/min), walking up-/downhill (0.06 kcal/min) and stair walking (upstairs: 0.13 kcal/min; downstairs: 0.29 kcal/min) and underestimated AEE of walking fast (-0.11 kcal/min) and jogging (-0.93 kcal/min). Our data suggest that the activity monitor using activity-dependent calculation models is more appropriate for predicting AEE in daily life than the activity monitor using a single regression model.

  9. Polymorphism of organic cation transporter 2 improves glucose-lowering effect of metformin via influencing its pharmacokinetics in Chinese type 2 diabetic patients.

    PubMed

    Hou, Wolin; Zhang, Dandan; Lu, Wei; Zheng, Taishan; Wan, Lili; Li, Qing; Bao, Yuqian; Liu, Fang; Jia, Weiping

    2015-02-01

    This study aimed to investigate how the organic cation transporter 2 nucleotide polymorphism at site 808 (G → T) affects metformin pharmacokinetics and its long-term anti-diabetic effect. A total of 220 newly diagnosed type 2 diabetes patients taking oral metformin were recruited, genotyped and then divided into three groups by SLC22A2 genotypes (G/G, G/T, T/T). Nine patients in the GG genotype group, five patients in the GT genotype group and four patients in the TT genotype group were randomly selected for the metformin pharmacokinetic study. A randomized cohort study with 1-year follow-up was performed to clarify the metformin pharmacodynamics. After 1 year, the decrease in glycosylated hemoglobin (HbA1c) levels in subjects with the heterozygous variant genotype (GT) was significantly greater than in those with the wild-type homozygote (-2.2 % in GT vs. -1.1 % in GG, P < 0.05) after adjustment for baseline HbA1c levels, exercise and diet in each group. There were also differences in the pharmacokinetic parameters (95 % confidence interval) of metformin between these two groups [area under the concentration-time curve (AUC)0-∞ 19.7 (15.7-23.8) vs. 14.3 (11.7-16.9) μg h/L; renal clearance (CLr) 16.8 (8.5-25.0) vs. 34.1 (24.9-43.2) L/h; tubular secretion clearance (CLt) 8.1 (2.2-18.1) vs. 22.7 (15.5-29.8) L/h; all P < 0.05]. Multivariate analysis further revealed that the presence of T alleles and gender were independent influencing factors of urine excretion of metformin (P < 0.05). As well as gender, the glucose-lowering efficiency of metformin can be enhanced by SLC22A2 808G > T variants through the delay of its transportation and CLr in Chinese type 2 diabetes populations.

  10. Tables of Transition Probabilities and Branching Ratios for Electric Dipole Transitions Between Arbitrary Levels of Hydrogen-Like Atoms

    NASA Technical Reports Server (NTRS)

    Omidvar, K.

    1980-01-01

    Branching ratios in hydrogen-like atoms due to electric-dipole transitions are tabulated for the initial principal and angular momentum quantum number n, lambda, and final principal and angular momentum quantum numbers n, lambda. In table 1, transition probabilities are given for transitions n, lambda, yields n, where sums have been made with respect to lambda. In this table, 2 or = n' or = 10, o or = lambda' or = n'-1, and 1 or = n or = n'-1. In addition, averages with respect to lambda' and sums with respect to n, and lifetimes are given. In table 2, branching ratios are given for transitions n' lambda' yields ni, where sums have been made with respect to lambda. In these tables, 2 or = n' or = 10, 0 or = lambda', n'-1, and 1 or = n or = n'-1. Averages with respect to lambda' are also given. In table 3, branching ratios are given for transitions n' lambda' yields in lambda, where 1 or = n or = 5, 0 or = lambda or = n-1, n n' or = 15, and 0 or = lambda' or = n(s), where n(s), is the smaller of the two numbers n'-1 and 6. Averages with respect to lambda' are given.

  11. Measurement of the Λ b cross section and the Λ ¯ b to Λ b ratio with J / ψ Λ decays in pp collisions at s = 7 TeV

    DOE PAGES

    Chatrchyan, S.; Khachatryan, V.; Sirunyan, A. M.; ...

    2012-05-31

    The Lambda(b) differential production cross section and the cross section ratio anti-Lambda(b)/Lambda(b) are measured as functions of transverse momentum pt(Lambda(b)) and rapidity abs(y(Lambda(b))) in pp collisions at sqrt(s) = 7 TeV using data collected by the CMS experiment at the LHC. The measurements are based on Lambda(b) decays reconstructed in the exclusive final state J/Psi Lambda, with the subsequent decays J/Psi to an opposite-sign muon pair and Lambda to proton pion, using a data sample corresponding to an integrated luminosity of 1.9 inverse femtobarns. The product of the cross section times the branching ratio for Lambda(b) to J/Psi Lambda versusmore » pt(Lambda(b)) falls faster than that of b mesons. The measured value of the cross section times the branching ratio for pt(Lambda(b)) > 10 GeV and abs(y(Lambda(b))) < 2.0 is 1.06 +/- 0.06 +/- 0.12 nb, and the integrated cross section ratio for anti-Lambda(b)/Lambda(b) is 1.02 +/- 0.07 +/- 0.09, where the uncertainties are statistical and systematic, respectively.« less

  12. {lambda}{sub b}{yields}p, {lambda} transition form factors from QCD light-cone sum rules

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

    Wang Yuming; Lue Caidian; Shen Yuelong

    2009-10-01

    Light-cone sum rules for the {lambda}{sub b}{yields}p, {lambda} transition form factors are derived from the correlation functions expanded by the twist of the distribution amplitudes of the {lambda}{sub b} baryon. In terms of the {lambda}{sub b} three-quark distribution amplitude models constrained by the QCD theory, we calculate the form factors at small momentum transfers and compare the results with those estimated in the conventional light-cone sum rules (LCSR) and perturbative QCD approaches. Our results indicate that the two different versions of sum rules can lead to the consistent numbers of form factors responsible for {lambda}{sub b}{yields}p transition. The {lambda}{sub b}{yields}{lambda}more » transition form factors from LCSR with the asymptotic {lambda} baryon distribution amplitudes are found to be almost 1 order larger than those obtained in the {lambda}{sub b}-baryon LCSR, implying that the preasymptotic corrections to the baryonic distribution amplitudes are of great importance. Moreover, the SU(3) symmetry breaking effects between the form factors f{sub 1}{sup {lambda}{sub b}}{sup {yields}}{sup p} and f{sub 1}{sup {lambda}{sub b}}{sup {yields}}{sup {lambda}} are computed as 28{sub -8}{sup +14}% in the framework of {lambda}{sub b}-baryon LCSR.« less

  13. Isolation and structure–function characterization of a signaling-active rhodopsin–G protein complex

    PubMed Central

    Gao, Yang; Westfield, Gerwin; Erickson, Jon W.; Cerione, Richard A.; Skiniotis, Georgios; Ramachandran, Sekar

    2017-01-01

    The visual photo-transduction cascade is a prototypical G protein–coupled receptor (GPCR) signaling system, in which light-activated rhodopsin (Rho*) is the GPCR catalyzing the exchange of GDP for GTP on the heterotrimeric G protein transducin (GT). This results in the dissociation of GT into its component αT–GTP and β1γ1 subunit complex. Structural information for the Rho*–GT complex will be essential for understanding the molecular mechanism of visual photo-transduction. Moreover, it will shed light on how GPCRs selectively couple to and activate their G protein signaling partners. Here, we report on the preparation of a stable detergent-solubilized complex between Rho* and a heterotrimer (GT*) comprising a GαT/Gαi1 chimera (αT*) and β1γ1. The complex was formed on native rod outer segment membranes upon light activation, solubilized in lauryl maltose neopentyl glycol, and purified with a combination of affinity and size-exclusion chromatography. We found that the complex is fully functional and that the stoichiometry of Rho* to GαT* is 1:1. The molecular weight of the complex was calculated from small-angle X-ray scattering data and was in good agreement with a model consisting of one Rho* and one GT*. The complex was visualized by negative-stain electron microscopy, which revealed an architecture similar to that of the β2-adrenergic receptor–GS complex, including a flexible αT* helical domain. The stability and high yield of the purified complex should allow for further efforts toward obtaining a high-resolution structure of this important signaling complex. PMID:28655769

  14. New 1982-1990 photometry of Lambda Andromedae and its 11-year cycle

    NASA Technical Reports Server (NTRS)

    Hall, Douglas S.; Henry, Gregory W.; Boehme, Dietmar; Brooks, Peter A.; Chang, Sandy; Dolzan, Ales; Fortier, George L.; Fried, Robert E.; Genet, Russell M.; Grim, Bruce S.

    1991-01-01

    The paper presents photoelectric photometry of Lambda And never before published, obtained between February 1982 and December 1990 at 29 different observatories. Then it is combined with all other photometry available (previously published, contained in the I.A.U. Commission 27 Archives, and obtained with the Vanderbilt 16-inch automatic telescope but not yet published), to yield a 14.8-year data base. Analysis reveals a long-term cycle in mean brightness, with a full range of 0.15 m and a period of 11.4 +/- 0.4 years. Because most of the new photometry was concentrated in the 1983-1984 observing season, this one well-defined light curve is analyzed with a two-spot model. Spot A keeps a 0.04 m amplitude throughout four rotation cycles whereas the amplitude of spot B diminishes from 0.09 m down almost to 0.03 m. The spot rotation periods were 55.9 d +/- 0.6 d and 52.8 d +/- 1.0 d, respectively.

  15. First observation and measurement of the resonant structure of the lambda_b->lambda_c pi-pi+pi- decay mode

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

    Azzurri, P.; Barria, P.; Ciocci, M.A.

    The authors present the first observation of the {Lambda}{sub b}{sup 0} {yields} {Lambda}{sub c}{sup +}{pi}{sup -}{pi}{sup +}{pi}{sup -} decay using data from an integrated luminosity of approximately 2.4 fb{sup -1} of p{bar p} collisions at {radical}s = 1.96 TeV, collected with the CDF II detector at the Fermilab Tevatron. They also present the first observation of the resonant decays {Lambda}{sub b}{sup 0} {yields} {Sigma}{sub c}(2455){sup 0} {pi}{sup +}{pi}{sup -} {yields} {Lambda}{sub c}{sup +}{pi}{sup -}{pi}{sup +}{pi}{sup -}, {Lambda}{sub b}{sup 0} {yields} {Sigma}{sub c}(2455){sup ++}{pi}{sup -}{pi}{sup -} {yields} {Lambda}{sub c}{sup +}{pi}{sup -}{pi}{sup +}{pi}{sup -}, {Lambda}{sub b}{sup 0} {yields} {Lambda}{sub c}(2595){sup +}{pi}{sup -}more » {yields} {Lambda}{sub c}{sup +}{pi}{sup -}{pi}{sup +}{pi}{sup -} and {Lambda}{sub b}{sup 0} {yields} {Lambda}{sub c}(2625){sup +}{pi}{sup -} {yields} {Lambda}{sub c}{sup +}{pi}{sup -}{pi}{sup +}{pi}{sup -}, and measure their relative branching ratios.« less

  16. Spin correlations in the {Lambda}{Lambda} and {Lambda}{Lambda}-bar systems generated in relativistic heavy-ion collisions

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

    Lyuboshitz, V. L.; Lyuboshitz, V. V., E-mail: Valery.Lyuboshitz@jinr.r

    2010-05-15

    Spin correlations for the {Lambda}{Lambda} and {Lambda}{Lambda}-bar pairs, generated in relativistic heavy-ion collisions, and related angular correlations at the joint registration of hadronic decays of two hyperons, in which space parity is not conserved, are analyzed. The correlation tensor components can be derived from the double angular distribution of products of two decays by the method of 'moments'. The properties of the 'trace' of the correlation tensor (a sum of three diagonal components), determining the relative fractions of the triplet states and singlet state of respective pairs, are discussed. Spin correlations for two identical particles ({Lambda}{Lambda}) and two nonidentical particlesmore » ({Lambda}{Lambda}-bar) are considered from the viewpoint of the conventional model of one-particle sources. In the framework of this model, correlations vanish at sufficiently large relative momenta. However, under these conditions, in the case of two nonidentical particles ({Lambda}{Lambda}-bar) a noticeable role is played by two-particle annihilation (two-quark, two-gluon) sources, which lead to the difference of the correlation tensor from zero. In particular, such a situation may arise when the system passes through the 'mixed phase.'« less

  17. Effect of training data size and noise level on support vector machines virtual screening of genotoxic compounds from large compound libraries.

    PubMed

    Kumar, Pankaj; Ma, Xiaohua; Liu, Xianghui; Jia, Jia; Bucong, Han; Xue, Ying; Li, Ze Rong; Yang, Sheng Yong; Wei, Yu Quan; Chen, Yu Zong

    2011-05-01

    Various in vitro and in-silico methods have been used for drug genotoxicity tests, which show limited genotoxicity (GT+) and non-genotoxicity (GT-) identification rates. New methods and combinatorial approaches have been explored for enhanced collective identification capability. The rates of in-silco methods may be further improved by significantly diversified training data enriched by the large number of recently reported GT+ and GT- compounds, but a major concern is the increased noise levels arising from high false-positive rates of in vitro data. In this work, we evaluated the effect of training data size and noise level on the performance of support vector machines (SVM) method known to tolerate high noise levels in training data. Two SVMs of different diversity/noise levels were developed and tested. H-SVM trained by higher diversity higher noise data (GT+ in any in vivo or in vitro test) outperforms L-SVM trained by lower noise lower diversity data (GT+ in in vivo or Ames test only). H-SVM trained by 4,763 GT+ compounds reported before 2008 and 8,232 GT- compounds excluding clinical trial drugs correctly identified 81.6% of the 38 GT+ compounds reported since 2008, predicted 83.1% of the 2,008 clinical trial drugs as GT-, and 23.96% of 168 K MDDR and 27.23% of 17.86M PubChem compounds as GT+. These are comparable to the 43.1-51.9% GT+ and 75-93% GT- rates of existing in-silico methods, 58.8% GT+ and 79% GT- rates of Ames method, and the estimated percentages of 23% in vivo and 31-33% in vitro GT+ compounds in the "universe of chemicals". There is a substantial level of agreement between H-SVM and L-SVM predicted GT+ and GT- MDDR compounds and the prediction from TOPKAT. SVM showed good potential in identifying GT+ compounds from large compound libraries based on higher diversity and higher noise training data.

  18. Association of SLC11A1 with tuberculosis interactions with NOS2A and TLR2 in African-Americans and Caucasians

    PubMed Central

    Velez, D.R.; Hulme, W.F.; Myers, J.L.; Stryjewski, M.E.; Abbate, E.; Estevan, R.; Patillo, S.G.; Gilbert, J.R.; Hamilton, C.D.; Scott, W.K.

    2010-01-01

    SETTING Host defense factors may influence the development of active tuberculosis (TB). OBJECTIVE To test variants in solute carrier family 11A, member 1 (SLC11A1), for an association with TB. METHODS A mixed case-control study of TB cases, relatives or close contact controls, consisting of 474 African-Americans (243 families) and 381 Caucasians (192 families), examined 13 SLC11A1 polymorphisms for association with pulmonary TB using generalized estimating equations adjusting for age and gender. RESULTS Two associations were observed in Caucasians (rs3731863, P = 0.03, and rs17221959, P = 0.04) and one in African-Americans (rs3731865, P = 0.05). Multilocus analyses between polymorphisms in SLC11A1 and 11 TB candidate genes detected interactions between SLC11A1 and inducible nitric oxide synthase (NOS2A) in Caucasians (rs3731863 [SLC11A1] × rs8073782 [NOS2A], P = 0.009; rs3731863 [SLC11A1] × rs17722851 [NOS2A], P = 0.007) and toll-like receptor 2 (TLR2) in African-Americans (rs3731865 [SLC11A1] x rs1816702, P = 0.005). CONCLUSIONS No association was detected with 5′(GT)n promoter polymorphism previously associated with lower SLC11A1 expression, rs17235409 (D543N), or rs17235416 (3′ TGTG insertion/deletion polymorphism). SLC11A1 polymorphism rs3731865 was associated with TB in African-Americans, consistent with previous findings in West Africans. These results suggest that variants in SLC11A1 increase susceptibility to pulmonary TB and interact with other variants that differ by race. PMID:19723394

  19. Staufen2 deficiency leads to impaired response to novelty in mice.

    PubMed

    Popper, Bastian; Demleitner, Antonia; Bolivar, Valerie J; Kusek, Gretchen; Snyder-Keller, Abigail; Schieweck, Rico; Temple, Sally; Kiebler, Michael A

    2018-04-01

    Staufen2 (Stau2) is a double-stranded RNA-binding protein (RBP) involved in posttranscriptional gene expression control in neurons. In flies, staufen contributes to learning and long-term memory formation. To study the impact of mammalian Stau2 on behavior, we generated a novel gene-trap mouse model that yields significant constitutive downregulation of Stau2 (Stau2 GT ). In order to investigate the effect of Stau2 downregulation on hippocampus-dependent behavior, we performed a battery of behavioral assays, i.e. open field, novel object recognition/location (NOR/L) and Barnes maze. Stau2 GT mice displayed reduced locomotor activity in the open field and altered novelty preference in the NOR and NOL paradigms. Adult Stau2 GT male mice failed to discriminate between familiar and newly introduced objects but showed enhanced spatial novelty detection. Additionally, we observed deficits in discriminating different spatial contexts in a Barnes maze assay. Together, our data suggest that Stau2 contributes to novelty preference and explorative behavior that is a driver for proper spatial learning in mice. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Amphetamine-induced incentive sensitization of sign-tracking behavior in adolescent and adult female rats

    PubMed Central

    Doremus-Fitzwater, Tamara L.; Spear, Linda P.

    2010-01-01

    Age-specific behavioral and neural characteristics may predispose adolescents to initiate and escalate use of alcohol and drugs. Adolescents may avidly seek novel experiences, including drugs of abuse, because of enhanced incentive motivation for drugs and natural rewards, perhaps especially when that incentive motivation is sensitized by prior drug exposure. Using a Pavlovian conditioned approach (PCA) procedure, sign-tracking (ST) and goal-tracking (GT) behavior was examined in amphetamine-sensitized and control adolescent and adult female Sprague-Dawley rats, with expression of elevated ST behavior used to index enhanced incentive motivation for reward-associated cues. Rats were first exposed to a sensitizing regimen of amphetamine injections (3.0 mg/kg/ml d-amphetamine per day) or given saline (0.9% w/v) once daily for 4 days. Expression of ST and GT was then examined over 8 days of PCA training consisting of 25 pairings of an 8-sec presentation of an illuminated lever immediately followed by response-independent delivery of a banana-flavored food pellet. Results showed that adults clearly displayed more ST behavior than adolescents, reflected via both more contacts with, and shorter latencies to approach, the lever. Prior amphetamine sensitization increased ST (but not GT) behaviors regardless of age. Thus, when indexed via ST, incentive motivation was found to be greater in adults than adolescents, with a prior history of amphetamine exposure generally sensitizing incentive motivation for cues predicting a food reward regardless of age. PMID:21534648

  1. Lmo4 in the Basolateral Complex of the Amygdala Modulates Fear Learning

    PubMed Central

    Maiya, Rajani; Kharazia, Viktor; Lasek, Amy W.; Heberlein, Ulrike

    2012-01-01

    Pavlovian fear conditioning is an associative learning paradigm in which mice learn to associate a neutral conditioned stimulus with an aversive unconditioned stimulus. In this study, we demonstrate a novel role for the transcriptional regulator Lmo4 in fear learning. LMO4 is predominantly expressed in pyramidal projection neurons of the basolateral complex of the amygdala (BLC). Mice heterozygous for a genetrap insertion in the Lmo4 locus (Lmo4gt/+), which express 50% less Lmo4 than their wild type (WT) counterparts display enhanced freezing to both the context and the cue in which they received the aversive stimulus. Small-hairpin RNA-mediated knockdown of Lmo4 in the BLC, but not the dentate gyrus region of the hippocampus recapitulated this enhanced conditioning phenotype, suggesting an adult- and brain region-specific role for Lmo4 in fear learning. Immunohistochemical analyses revealed an increase in the number of c-Fos positive puncta in the BLC of Lmo4gt/+ mice in comparison to their WT counterparts after fear conditioning. Lastly, we measured anxiety-like behavior in Lmo4gt/+ mice and in mice with BLC-specific downregulation of Lmo4 using the elevated plus maze, open field, and light/dark box tests. Global or BLC-specific knockdown of Lmo4 did not significantly affect anxiety-like behavior. These results suggest a selective role for LMO4 in the BLC in modulating learned but not unlearned fear. PMID:22509321

  2. Parkes radio searches of Fermi gamma-ray sources and millisecond pulsar discoveries

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

    Camilo, F.; Kerr, M.; Ray, P. S.

    In a search with the Parkes radio telescope of 56 unidentified Fermi-Large Area Telescope (LAT) gamma-ray sources, we have detected 11 millisecond pulsars (MSPs), 10 of them discoveries, of which five were reported by Kerr et al. We did not detect radio pulsations from six other pulsars now known in these sources. We also describe the completed survey, which included multiple observations of many targets conducted to minimize the impact of interstellar scintillation, acceleration effects in binary systems, and eclipses. We consider that 23 of the 39 remaining sources may still be viable pulsar candidates. Furthermore, we present timing solutions and polarimetry for five of the MSPs and gamma-ray pulsations for PSR J1903–7051 (pulsations for five others were reported in the second Fermi-LAT catalog of gamma-ray pulsars). Two of the new MSPs are isolated and five are inmore » $$\\gt 1$$ day circular orbits with 0.2–0.3 $${M}_{\\odot }$$ presumed white dwarf companions. PSR J0955–6150, in a 24 day orbit with a $$\\approx 0.25$$ $${M}_{\\odot }$$ companion but eccentricity of 0.11, belongs to a recently identified class of eccentric MSPs. PSR J1036–8317 is in an 8 hr binary with a $$\\gt 0.14$$ $${M}_{\\odot }$$ companion that is probably a white dwarf. PSR J1946–5403 is in a 3 hr orbit with a $$\\gt 0.02$$ $${M}_{\\odot }$$ companion with no evidence of radio eclipses.« less

  3. Parkes radio searches of Fermi gamma-ray sources and millisecond pulsar discoveries

    DOE PAGES

    Camilo, F.; Kerr, M.; Ray, P. S.; ...

    2015-09-02

    In a search with the Parkes radio telescope of 56 unidentified Fermi-Large Area Telescope (LAT) gamma-ray sources, we have detected 11 millisecond pulsars (MSPs), 10 of them discoveries, of which five were reported by Kerr et al. We did not detect radio pulsations from six other pulsars now known in these sources. We also describe the completed survey, which included multiple observations of many targets conducted to minimize the impact of interstellar scintillation, acceleration effects in binary systems, and eclipses. We consider that 23 of the 39 remaining sources may still be viable pulsar candidates. Furthermore, we present timing solutions and polarimetry for five of the MSPs and gamma-ray pulsations for PSR J1903–7051 (pulsations for five others were reported in the second Fermi-LAT catalog of gamma-ray pulsars). Two of the new MSPs are isolated and five are inmore » $$\\gt 1$$ day circular orbits with 0.2–0.3 $${M}_{\\odot }$$ presumed white dwarf companions. PSR J0955–6150, in a 24 day orbit with a $$\\approx 0.25$$ $${M}_{\\odot }$$ companion but eccentricity of 0.11, belongs to a recently identified class of eccentric MSPs. PSR J1036–8317 is in an 8 hr binary with a $$\\gt 0.14$$ $${M}_{\\odot }$$ companion that is probably a white dwarf. PSR J1946–5403 is in a 3 hr orbit with a $$\\gt 0.02$$ $${M}_{\\odot }$$ companion with no evidence of radio eclipses.« less

  4. UTILIZING SYNTHETIC UV SPECTRA TO EXPLORE THE PHYSICAL BASIS FOR THE CLASSIFICATION OF LAMBDA BOÖTIS STARS

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

    Cheng, Kwang-Ping; Johnson, Dustin M.; Tarbell, Erik S.

    2016-04-15

    Lambda Boo-type stars are a group of late B to early F-type Population I dwarfs that show mild to extreme deficiencies of iron-peak elements (up to 2 dex), but their C, N, O, and S abundances are near solar. This intriguing stellar class has recently regained the spotlight because of the directly imaged planets around a confirmed Lambda Boo star, HR 8799, and a suggested Lambda Boo star, Beta Pictoris. The discovery of a giant asteroid belt around Vega, another possible Lambda Boo star, also suggests hidden planets. The possible link between Lambda Boo stars and planet-bearing stars motivates usmore » to study Lambda Boo stars systematically. Since the peculiar nature of the prototype Lambda Boötis was first noticed in 1943, Lambda Boo candidates published in the literature have been selected using widely different criteria. In order to determine the origin of Lambda Boo stars’ unique abundance pattern and to better discriminate between theories explaining the Lambda Boo phenomenon, a consistent working definition of Lambda Boo stars is needed. We have re-evaluated all published Lambda Boo candidates and their available ultraviolet and visible spectra. In this paper, using observed and synthetic spectra, we explore the physical basis for the classification of Lambda Boo stars, and develop quantitative criteria that discriminate metal-poor stars from bona fide Lambda Boo stars. Based on these stricter Lambda Boo classification criteria, we conclude that neither Beta Pictoris nor Vega should be classified as Lambda Boo stars.« less

  5. Effect of Angum gum in combination with tragacanth gum on rheological and sensory properties of ketchup.

    PubMed

    Komeilyfard, Ahmadreza; Fazel, Mohammad; Akhavan, Hamidreza; Mousakhani Ganjeh, Alireza

    2017-04-01

    The aim of this study was to evaluate the effect of Angum gum (AnG) alone and in combination with tragacanth gum (TG) on the stability, texture, sensory, and rheological properties of tomato ketchup. AnG, TG, and Angum gum and tragacanth gum mixture (AnGT; 1:1 ratio) were added at levels of 0.5, 1, and 1.5%. Ten tomato ketchup formulations were produced: control (without hydrocolloid), AnG (0.5-1.5%), TG (0.5-1.5%), AnGT (0.5-1.5%). It was observed that the hydrocolloids addition to tomato ketchup significantly decreased the Bostwick consistency value and serum separation at 2200, 5000, and 8800 g. Textural properties of tomato ketchup by using back extrusion test and particle size analysis were significantly increased with hydrocolloid addition. All tomato ketchup formulations showed shear thinning behavior and the addition of hydrocolloids increased apparent viscosity. The power law and Herschel-Bulkley models were successfully fitted with experimental data. The flow behavior indices of Herschel-Bulkley and power law models were changed in the range of 0.19-0.24 and 0.14-0.30, respectively. The consistency coefficients of these models were in the range of 16.31-79.57 and 11.19-146.06 Pa s n , respectively. The storage modulus (G') of all tomato ketchups was higher than the loss modulus (G″). Hydrocolloid addition showed no significant effect on the color indices (L*, a*, b*, hue angle, chroma, and total color differences) of tomato ketchup. The overall acceptability of 1.5% AnG, 0.5% TG, 1 and 1.5% AnGT were significantly higher than other samples. Therefore, AnG can be used alone and in combination with TG as stabilizer in tomato ketchup. The consistency of tomato ketchup is an important attribute from both engineering and consumer viewpoints. It was observed that addition of TG, AnG, and AnGT to tomato ketchups significantly decreased their Bostwick consistency values and their serum separation. In addition, hydrocolloid addition showed no significant effect on the color indices (L*, a*, b*, Hue angle, chroma, and total color differences) of samples. Also, the panelists gave greatest sensory scores in term of overall acceptance to ketchups containing 1% AnGT than other samples. © 2016 Wiley Periodicals, Inc.

  6. Geological Carbon Sequestration Storage Resource Estimates for the Ordovician St. Peter Sandstone, Illinois and Michigan Basins, USA

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

    Barnes, David; Ellett, Kevin; Leetaru, Hannes

    The Cambro-Ordovician strata of the Midwest of the United States is a primary target for potential geological storage of CO2 in deep saline formations. The objective of this project is to develop a comprehensive evaluation of the Cambro-Ordovician strata in the Illinois and Michigan Basins above the basal Mount Simon Sandstone since the Mount Simon is the subject of other investigations including a demonstration-scale injection at the Illinois Basin Decatur Project. The primary reservoir targets investigated in this study are the middle Ordovician St Peter Sandstone and the late Cambrian to early Ordovician Knox Group carbonates. The topic of thismore » report is a regional-scale evaluation of the geologic storage resource potential of the St Peter Sandstone in both the Illinois and Michigan Basins. Multiple deterministic-based approaches were used in conjunction with the probabilistic-based storage efficiency factors published in the DOE methodology to estimate the carbon storage resource of the formation. Extensive data sets of core analyses and wireline logs were compiled to develop the necessary inputs for volumetric calculations. Results demonstrate how the range in uncertainty of storage resource estimates varies as a function of data availability and quality, and the underlying assumptions used in the different approaches. In the simplest approach, storage resource estimates were calculated from mapping the gross thickness of the formation and applying a single estimate of the effective mean porosity of the formation. Results from this approach led to storage resource estimates ranging from 3.3 to 35.1 Gt in the Michigan Basin, and 1.0 to 11.0 Gt in the Illinois Basin at the P10 and P90 probability level, respectively. The second approach involved consideration of the diagenetic history of the formation throughout the two basins and used depth-dependent functions of porosity to derive a more realistic spatially variable model of porosity rather than applying a single estimate of porosity throughout the entire potential reservoir domains. The second approach resulted in storage resource estimates of 3.0 to 31.6 Gt in the Michigan Basin, and 0.6 to 6.1 Gt in the Illinois Basin. The third approach attempted to account for the local-scale variability in reservoir quality as a function of both porosity and permeability by using core and log analyses to calculate explicitly the net effective porosity at multiple well locations, and interpolate those results throughout the two basins. This approach resulted in storage resource estimates of 10.7 to 34.7 Gt in the Michigan Basin, and 11.2 to 36.4 Gt in the Illinois Basin. A final approach used advanced reservoir characterization as the most sophisticated means to estimating storage resource by defining reservoir properties for multiple facies within the St Peter formation. This approach was limited to the Michigan Basin since the Illinois Basin data set did not have the requisite level of data quality and sampling density to support such an analysis. Results from this approach led to storage resource estimates of 15.4 Gt to 50.1 Gt for the Michigan Basin. The observed variability in results from the four different approaches is evaluated in the context of data and methodological constraints, leading to the conclusion that the storage resource estimates from the first two approaches may be conservative, whereas the net porosity based approaches may over-estimate the resource.« less

  7. Organization of genes for transcription and translation in the rif region of the Escherichia coli chromosome. [uv radiation

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

    Yamamoto, M.; Nomura, M.

    1979-01-01

    The lambda rif/sup d/18 transducing phage is known to carry several genes for components of transcriptional and translational machineries; these genes are clustered in the rif region at 88 min on the Escherichia coli genetic map. They include a set of genes for rRNA's (rrnB), a gene for spacer tRNA, tRNA/sub 2//sup Glu/(tgtB), one of the two genes for EF-TU (tufB), genes for four ribosomal proteins (rplK, A, J, and L), genes for the ..beta.. and ..beta..' subunits of RNA polymerase (rpoB and rpoC), and genes for three tRNA's (tyrU, gluT, and thrT). An additional tRNA gene (subsequently identified asmore » thrU by Landy and his co-workers) and a gene for a protein (protein U) with unknown functions were found to be carried by lambda rif/sup d/18. We analyzed the organization of these genes by using various deletion and hybrid phages derived from lambda rif/sup d/18 and lambda rif/sup d/12, a phage related to lambda rif/sup d/18. The expression of various genes was examined in uv-irradiated cells infected with these transducing phages. Two main conclusions were obtained. First, the four tRNA genes are not cotranscribed with the genes in rrnB, even though these tRNA genes are located close to the distal end of rrnB. Second, the four ribosomal protein genes are organized into two separate transcriptional units; rplK and A are in one unit and rplJ and L are in the second unit.« less

  8. Prey Foraging Under Sublethal Lambda-Cyhalothrin Exposure on Pyrethroid-Susceptible and -Resistant Lady Beetles (Eriopis connexa (Coleoptera: Coccinelidae)).

    PubMed

    D'Ávila, V A; Reis, L C; Barbosa, W F; Cutler, G C; Torres, J B; Guedes, R N C

    2018-05-28

    Sublethal insecticide exposure may affect foraging of insects, including natural enemies, although the subject is usually neglected. The lady beetle Eriopis connexa (Germar, 1824) (Coleoptera: Coccinelidae) is an important predator of aphids with existing pyrethroid-resistant populations that are undergoing scrutiny for potential use in pest management systems characterized by frequent insecticide use. However, the potential effect of sublethal pyrethroid exposure on this predator's foraging activity has not yet been assessed and may compromise its use in biological control. Therefore, our objective was to assess the effect of sublethal lambda-cyhalothrin exposure on three components of the prey foraging activity (i.e., walking, and prey searching and handling), in both pyrethroid-susceptible and -resistant adults of E. connexa. Both lady beetle populations exhibited similar walking patterns without insecticide exposure in noncontaminated arenas, but in partially contaminated arenas walking differed between strains, such that the resistant insects exhibited greater walking activity. Behavioral avoidance expressed as repellence to lambda-cyhalothrin was not observed for either the susceptible or resistant populations of E. connexa, but the insecticide caused avoidance by means of inducing irritability in 40% of the individuals, irrespective of the strain. Insects remained in the insecticide-contaminated portion of the arena for extended periods resulting in greater exposure. Although lambda-cyhalothrin exposure did not affect prey searching by susceptible lady beetles, prey searching was extended for exposed resistant predators. In contrast, prey handling was not affected by population or by lambda-cyhalothrin exposure. Thus, sublethal exposure to the insecticide in conjunction with the insect resistance profile can affect prey foraging with pyrethroid-exposed resistant predators exhibiting longer prey searching time associated with higher walking activity reducing its predatory performance.

  9. GEMINI-TITAN (GT)-4 - EARTH-SKY - OUTER SPACE

    NASA Image and Video Library

    1965-06-01

    S65-34670 (3-7 June 1965) --- Richat crater in northwest Africa taken from the Gemini-4 spacecraft. Photograph was taken with a modified 70mm Hasselblad camera, using Eastman color film, ASA 64, at a lens setting of 250th of a second at f/11.

  10. 46 CFR 11.317 - Requirements to qualify for an STCW endorsement as master of vessels of less than 500 GT limited...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... of this subpart. (iii) Proficiency in survival craft and rescue boats other than fast rescue boats (PSC) or proficiency in survival craft and rescue boats other than lifeboats and fast rescue boats (PSC...

  11. Rayleigh lidar observations of gravity wave activity in the stratosphere and lower mesosphere

    NASA Technical Reports Server (NTRS)

    Miller, M. S.; Gardner, C. S.; Liu, C. H.

    1987-01-01

    Forty-two monochromatic gravity wave events were observed in the 25 to 55 km altitude region during 16 nights of Rayleigh lidar measurements at Poker Flat, Alaska and Urbana, Illinois. The measured wave parameters were compared to previous radar and lidar measurements of gravity wave activity. Vertical wavelengths, lambda(z), between 2 and 11.5 km with vertical phase velocities, c(z), between 0.1 and 1 m/s were observed. Measured values of lambda(z) and c(z) were used to infer observed wave periods, T(ob), between 50 and 1000 minutes and horizontal wavelengths, lambda(x), from 25 to 2000 km. Dominant wave activity was found at vertical wavelengths between 2 to 4 km and 7 to 10 km. No seasonal variations were evident in the observed wave parameters. Vertical and horizontal wavelengths showed a clear tendency to increase with T(ob), which is consistent with recent sodium lidar studies of monochromatic wave events near the mesopause. Measured power law relationships between the wave parameters were lambda(z) varies as T(ob) sup 0.96, lambda(x) varies as T(ob) sup 1.8, and c(z) varies as T(ob) sup -0.85. The kinetic energy calculated for the monochromatic wave events varied as k(z) sup -2, k(x) sup -1, and f(ob) sup -1.7. The atmospheric scale heights calculated for each observation date range from 6.5 to 7.6 km with a mean value of 7 km. The increase of rms wind perturbations with altitude indicated an amplitude growth length of 20.9 km. The altitude profile of kinetic energy density decreased with height, suggesting that waves in this altitude region were subject to dissipation or saturation effects.

  12. Heme oxygenase up-regulation under ultraviolet-B radiation is not epigenetically restricted and involves specific stress-related transcriptions factors.

    PubMed

    Santa-Cruz, Diego; Pacienza, Natalia; Zilli, Carla; Pagano, Eduardo; Balestrasse, Karina; Yannarelli, Gustavo

    2017-08-01

    Heme oxygenase-1 (HO-1) plays a protective role against oxidative stress in plants. The mechanisms regulating its expression, however, remain unclear. Here we studied the methylation state of a GC rich HO-1 promoter region and the expression of several stress-related transcription factors (TFs) in soybean plants subjected to ultraviolet-B (UV-B) radiation. Genomic DNA and total RNA were isolated from leaves of plants irradiated with 7.5 and 15kJm-2 UV-B. A 304bp HO-1 promoter region was amplified by PCR from sodium bisulfite-treated DNA, cloned into pGEMT plasmid vector and evaluated by DNA sequencing. Bisulfite sequencing analysis showed similar HO-1 promoter methylation levels in control and UV-B-treated plants (C: 3.4±1.3%; 7.5: 2.6±0.5%; 15: 3.1±1.1%). Interestingly, HO-1 promoter was strongly unmethylated in control plants. Quantitative RT-PCR analysis of TFs showed that GmMYB177, GmMYBJ6, GmWRKY21, GmNAC11, GmNAC20 and GmGT2A but not GmWRK13 and GmDREB were induced by UV-B radiation. The expression of several TFs was also enhanced by hemin, a potent and specific HO inducer, inferring that they may mediate HO-1 up-regulation. These results suggest that soybean HO-1 gene expression is not epigenetically regulated. Moreover, the low level of HO-1 promoter methylation suggests that this antioxidant enzyme can rapidly respond to environmental stress. Finally, this study has identified some stress-related TFs involved in HO-1 up-regulation under UV-B radiation. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Necdin, a Prader-Willi syndrome candidate gene, regulates gonadotropin-releasing hormone neurons during development.

    PubMed

    Miller, Nichol L G; Wevrick, Rachel; Mellon, Pamela L

    2009-01-15

    Prader-Willi syndrome (PWS) is a complex genetic disorder characterized by hyperphagia, obesity and hypogonadotrophic hypogonadism, all highly suggestive of hypothalamic dysfunction. The NDN gene, encoding the MAGE family protein, necdin, maps to the PWS chromosome region and is highly expressed in mature hypothalamic neurons. Adult mice lacking necdin have reduced numbers of gonadotropin-releasing hormone (GnRH) neurons, but the mechanism for this reduction is unknown. Herein, we show that, although necdin is not expressed in an immature, migratory GnRH neuronal cell line (GN11), high levels are present in a mature GnRH neuronal cell line (GT1-7). Furthermore, overexpression of necdin activates GnRH transcription through cis elements bound by the homeodomain repressor Msx that are located in the enhancer and promoter of the GnRH gene, and knock-down of necdin expression reduces GnRH gene expression. In fact, overexpression of Necdin relieves Msx repression of GnRH transcription through these elements and necdin co-immunoprecipitates with Msx from GnRH neuronal cells, indicating that necdin may activate GnRH gene expression by preventing repression of GnRH gene expression by Msx. Finally, necdin is necessary for generation of the full complement of GnRH neurons during mouse development and extension of GnRH axons to the median eminence. Together, these results indicate that lack of necdin during development likely contributes to the hypogonadotrophic hypogonadal phenotype in individuals with PWS.

  14. Necdin, a Prader–Willi syndrome candidate gene, regulates gonadotropin-releasing hormone neurons during development

    PubMed Central

    Miller, Nichol L.G.; Wevrick, Rachel; Mellon, Pamela L.

    2009-01-01

    Prader–Willi syndrome (PWS) is a complex genetic disorder characterized by hyperphagia, obesity and hypogonadotrophic hypogonadism, all highly suggestive of hypothalamic dysfunction. The NDN gene, encoding the MAGE family protein, necdin, maps to the PWS chromosome region and is highly expressed in mature hypothalamic neurons. Adult mice lacking necdin have reduced numbers of gonadotropin-releasing hormone (GnRH) neurons, but the mechanism for this reduction is unknown. Herein, we show that, although necdin is not expressed in an immature, migratory GnRH neuronal cell line (GN11), high levels are present in a mature GnRH neuronal cell line (GT1-7). Furthermore, overexpression of necdin activates GnRH transcription through cis elements bound by the homeodomain repressor Msx that are located in the enhancer and promoter of the GnRH gene, and knock-down of necdin expression reduces GnRH gene expression. In fact, overexpression of Necdin relieves Msx repression of GnRH transcription through these elements and necdin co-immunoprecipitates with Msx from GnRH neuronal cells, indicating that necdin may activate GnRH gene expression by preventing repression of GnRH gene expression by Msx. Finally, necdin is necessary for generation of the full complement of GnRH neurons during mouse development and extension of GnRH axons to the median eminence. Together, these results indicate that lack of necdin during development likely contributes to the hypogonadotrophic hypogonadal phenotype in individuals with PWS. PMID:18930956

  15. Bivariate- distribution for transition matrix elements in Breit-Wigner to Gaussian domains of interacting particle systems.

    PubMed

    Kota, V K B; Chavda, N D; Sahu, R

    2006-04-01

    Interacting many-particle systems with a mean-field one-body part plus a chaos generating random two-body interaction having strength lambda exhibit Poisson to Gaussian orthogonal ensemble and Breit-Wigner (BW) to Gaussian transitions in level fluctuations and strength functions with transition points marked by lambda = lambda c and lambda = lambda F, respectively; lambda F > lambda c. For these systems a theory for the matrix elements of one-body transition operators is available, as valid in the Gaussian domain, with lambda > lambda F, in terms of orbital occupation numbers, level densities, and an integral involving a bivariate Gaussian in the initial and final energies. Here we show that, using a bivariate-t distribution, the theory extends below from the Gaussian regime to the BW regime up to lambda = lambda c. This is well tested in numerical calculations for 6 spinless fermions in 12 single-particle states.

  16. Lambda phage-based vaccine induces antitumor immunity in hepatocellular carcinoma.

    PubMed

    Iwagami, Yoshifumi; Casulli, Sarah; Nagaoka, Katsuya; Kim, Miran; Carlson, Rolf I; Ogawa, Kosuke; Lebowitz, Michael S; Fuller, Steve; Biswas, Biswajit; Stewart, Solomon; Dong, Xiaoqun; Ghanbari, Hossein; Wands, Jack R

    2017-09-01

    Hepatocellular carcinoma (HCC) is a difficult to treat tumor with a poor prognosis. Aspartate β-hydroxylase (ASPH) is a highly conserved enzyme overexpressed on the cell surface of both murine and human HCC cells. We evaluated therapeutic effects of nanoparticle lambda (λ) phage vaccine constructs against ASPH expressing murine liver tumors. Mice were immunized before and after subcutaneous implantation of a syngeneic BNL HCC cell line. Antitumor actively was assessed by generation of antigen specific cellular immune responses and the identification of tumor infiltrating lymphocytes. Prophylactic and therapeutic immunization significantly delayed HCC growth and progression. ASPH-antigen specific CD4+ and CD8+ lymphocytes were identified in the spleen of tumor bearing mice and cytotoxicity was directed against ASPH expressing BNL HCC cells. Furthermore, vaccination generated antigen specific Th1 and Th2 cytokine secretion by immune cells. There was widespread necrosis with infiltration of CD3+ and CD8+ T cells in HCC tumors of λ phage vaccinated mice compared to controls. Moreover, further confirmation of anti-tumor effects on ASPH expressing tumor cell growth were obtained in another murine syngeneic vaccine model with pulmonary metastases. These observations suggest that ASPH may serve as a highly antigenic target for immunotherapy.

  17. Green fluorescent protein as a reporter of gene expression and protein localization.

    PubMed

    Kain, S R; Adams, M; Kondepudi, A; Yang, T T; Ward, W W; Kitts, P

    1995-10-01

    The green fluorescent protein (GFP) from the jellyfish Aequorea victoria is rapidly becoming an important reporter molecule for monitoring gene expression and protein localization in vivo, in situ and in real time. GFP emits bright green light (lambda max = 509 nm) when excited with UV or blue light (lambda max = 395 nm, minor peak at 470 nm). The fluorescence excitation and emission spectra of GFP are similar to those of fluorescein, and the conditions used to visualize this fluorophore are also suitable for GFP. Unlike other bioluminescent reporters, the chromophore in GFP is intrinsic to the primary structure of the protein, and GFP fluorescence does not require a substrate or cofactor. GFP fluorescence is stable, species-independent and can be monitored non-invasively in living cells and, in the case of transparent organisms, whole animals. Here we demonstrate GFP fluorescence in bacterial and mammalian cells and introduce our Living Colors line of GFP reporter vectors, GFP protein and anti-GFP antiserum. The reporter vectors for GFP include a promoterless GFP vector for monitoring the expression of cloned promoters/enhancers in mammalian cells and a series of six vectors for creating fusion protein to either the N or C terminus of GFP.

  18. Room temperature synthesis of ReS2 through aqueous perrhenate sulfidation.

    PubMed

    Borowiec, Joanna; Gillin, William P; Willis, Maureen; Boi, Filippo; He, Yi; Wen, Jiqiu; Wang, Shanling; Schulz, Leander

    2017-12-29

    In this study, a direct sulfidation reaction of ammonium perrhenate (NH<sub>4</sub>ReO<sub>4</sub>) leading to a synthesis of rhenium disulfide (ReS<sub>2</sub>) is demonstrated. These finding reveal the first example of a simplistic bottom-up approach to the chemical synthesis of crystalline ReS<sub>2</sub>. The reaction presented here takes place at room temperature, in an ambient and solvent-free environment and without the necessity of a catalyst. The atomic composition and structure of the as-synthesized product were characterized using several analysis techniques including energy dispersive X-ray (EDX) spectroscopy, X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), transmission electron microscopy (TEM), Raman spectroscopy, thermogravimetric analysis (TGA) and differential scannig calorimetry (DSC). The results indicated the formation of a lower symmetry (1T<sub>d</sub>) ReS<sub>2</sub> with a low degree of layer stacking. © 2017 IOP Publishing Ltd.

  19. Immature surface Ig+ B cells can continue to rearrange kappa and lambda L chain gene loci

    PubMed Central

    1993-01-01

    Pro and pre B cells possess the long-term capacity to proliferate in vitro on stromal cells and interleukin 7 (IL-7) and can differentiate to surface immunoglobulin (sIg+) cells upon removal of IL-7 from the cultures. A key event in this differentiation is the extensive cell loss due to apoptosis. Because the proto-oncogene bcl-2 can promote cell survival, we established pre-B cell lines from E mu-bcl-2 transgenic mice. These pre-B cells have the same properties as those derived from non-bcl-2 transgenic mice except that they do not die by apoptosis. This allowed us to study the fate of newly formed B cells in vitro for a longer period of time. Here we show that early during the differentiation of pre-B cells, upregulation of RAG-1 and RAG-2 expression go hand in hand with rearrangements of the Ig gene loci. Moreover, the newly formed sIg+ B cells continue to express RAG-1 and RAG-2 and continue to rearrange L chain gene loci, even in the absence of proliferation, in an orderly fashion, so that kappa L+ sIg+ cells can become lambda L+ sIg+ or sIg- cells, whereas lambda L+ sIg+ cells can become sIg-, but not kappa L+ sIg+ cells. Thus, deposition of a complete Ig molecule on the surface of a B cell does not automatically stop the Ig-rearrangement machinery. PMID:8376934

  20. Long-range restriction map of human chromosome 22q11-22q12 between the lambda immunoglobulin locus and the Ewing sarcoma breakpoint

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

    McDermid, H.E.; Budarf, M.L.; Emanuel, B.S.

    1993-11-01

    A long-range restriction map of the region between the immunoglobulin lambda locus and the Ewing sarcoma breakpoint has been constructed using the rare-cutting enzymes NotI, NruI, AscI, and BsiWI. The map spans approximately 11,000 kb and represents about one-fifth of the long arm of chromosome 22. Thirty-nine markers, including seven NotI junction clones as well as numerous genes and anonymous sequences, were mapped to the region with a somatic cell hybrid panel. These probes were then used to produce the map. The seven NotI junction clones each identified a possible CpG island. The breakpoints of the RAJ5 hybrid and themore » Ewing sarcoma t(11;22) were also localized in the resulting map. This physical map will be useful in studying chromosomal rearrangements in the region, as well as providing the details to examine the fidelity of the YAC and cosmid contigs currently under construction. Comparisons of this physical map to genetic and radiation hybrid maps are discussed. 52 refs., 7 figs., 3 tabs.« less

  1. Spectroscopic Investigation of p-Shell Lambda Hypernuclei by the (e,e'K +) Reaction

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

    Chen, Chunhua

    2014-08-01

    Hypernuclear spectroscopy is a powerful tool to investigate Lambda-N interaction. Compared with other Lambda hypernuclei productions, electroproduction via the (e,e'K+) reaction has the advantage of exciting states deeply inside of the hypernucleus and achieving sub-MeV energy resolution. The E05-115 experiment, which was successfully performed in 2009, is the third generation hypernuclear experiment in JLab Hall C. A new splitter magnet and electron spectrometer were installed, and beam energy of 2.344 GeV was selected in this experiment. These new features gave better field uniformity, optics quality and made the tilt method more effective in improving yield-to-background ratio. The magnetic optics ofmore » the spectrometers were carefully studied with GEANT simulation, and corrections were applied to compensate for the fringe field cross talk between the compact spectrometer magnets. The non-linear least chi-squared method was used to further calibrate the spectrometer with the events from Lambda, Sigma0 and B12Lambda and uniform magnetic optics as well as precise kinematics were achieved. Several p-shell Lambda hypernuclear spectra, including B 12 Λ, Be 10 Λ, He 7 Λ, were obtained with high energy resolution and good accuracy. For B 12 Λ, eight peaks were recognized with the resolution of ~540keV (FWHM), and the ground state binding energy was obtained as 11.529 ± 0.012(stat.) ± 0.110(syst.) MeV. Be 10 Λ, twelve peaks were recognized with the resolution of ~520keV (FWHM), and the binding energy of the ground state was determined as 8.710 ± 0.059(stat.) ± 0.114(syst.) MeV. For He 7 Λ, three peaks were recognized with the resolution of ~730keV, and the ground state binding energy was obtained as 5.510 ± 0.050(stat.) ± 0.120(syst.) MeV. Compared with the published data of B 12 Λ from the JLab Hall A experiment, four extra peaks were fitted and interpreted thanks to the highest ever energy resolution and sufficient statistics. The determined binding energy of Be 10 Λ provides new information on charge symmetry breaking effect in the Lambda-N interaction. Compared with the results of He7Lambda from the E01-011 experiment, the ground state position is consistent with 4 times more statistics, and two extra peaks corresponding to excited states were recognized.« less

  2. Expression profiles of a MhCTR1 gene in relation to banana fruit ripening.

    PubMed

    Hu, Huei-Lin; Do, Yi-Yin; Huang, Pung-Ling

    2012-07-01

    The banana (Musa spp.) is a typical climacteric fruit of high economic importance. The development of bananas from maturing to ripening is characterized by increased ethylene production accompanied by a respiration burst. To elucidate the signal transduction pathway involved in the ethylene regulation of banana ripening, a gene homologous to Arabidopsis CTR1 (constitutive triple response 1) was isolated from Musa spp. (Hsien Jin Chiao, AAA group) and designated as MhCTR1. MhCTR1 spans 11.5 kilobases and consists of 15 exons and 14 introns with consensus GT-AG nucleotides situated at their boundaries. MhCTR1 encodes a polypeptide of 805 amino acid residues with a calculated molecular weight of 88.6 kDa. The deduced amino acid sequence of MhCTR1 demonstrates 55%, 56% and 55% homology to AtCTR1, RhCTR1, and LeCTR1, respectively. MhCTR1 is expressed mostly in the mature green pulp and root organs. During fruit development MhCTR1 expression increases just before ethylene production rises. Moreover, MhCTR1 expression was detected mainly in the pulps at ripening stage 3, and correlated with the onset of peel yellowing, while MhCTR1 was constitutively expressed in the peels. MhCTR1 expression could be induced by ethylene treatment (0.01 μL L(-1)), and MhCTR1 expression decreased in both peel and pulp 24 h after treatment. Overall, changes observed in MhCTR1 expression in the pulp closely related to the regulation of the banana ripening process. Copyright © 2012. Published by Elsevier Masson SAS.

  3. ASTRONAUT JAMES A. LOVELL, JR. - PRELAUNCH - GT-12 - LEAVE TRAILER - CAPE

    NASA Image and Video Library

    1966-11-11

    S66-59974 (11 Nov. 1966) --- Prime crew for the Gemini-12 spaceflight, astronauts James A. Lovell Jr., (leading), command pilot, and Edwin E. Aldrin Jr., pilot, leave the suiting trailer at Launch Complex 16 during prelaunch countdown. Moments later they entered a transport van which carried them to Pad 19 and their waiting spacecraft. The liftoff was at 3:46 p.m. (EST), Nov. 11, 1966. Photo credit: NASA

  4. Functional SNPs of INCENP Affect Semen Quality by Alternative Splicing Mode and Binding Affinity with the Target Bta-miR-378 in Chinese Holstein Bulls

    PubMed Central

    Zhang, Yan; Jiang, Qiang; Huang, Jinming; Ju, Zhihua; Wang, Xiuge; Zhong, Jifeng; Wang, Changfa

    2016-01-01

    Inner centromere protein (INCENP) plays an important role in mitosis and meiosis as the main member of chromosomal passenger protein complex (CPC). To investigate the functional markers of the INCENP gene associated with semen quality, the single nucleotide polymorphisms (SNPs) g.19970 A>G and g.34078 T>G were identified and analyzed. The new splice variant INCENP-TV is characterized by the deletion of exon 12. The g.19970 A>G in the exonic splicing enhancer (ESE) motif region results in an aberrant splice variant by constructing two minigene expression vectors using the pSPL3 exon capturing vector and transfecting vectors into MLTC-1 cells. INCENP-TV was more highly expressed than INCENP-reference in adult bull testes. The g.34078 T>G located in the binding region of bta-miR-378 could affect the expression of INCENP, which was verified by luciferase assay. To analyze comprehensively the correlation of SNPs with sperm quality, haplotype combinations constructed by g.19970 A>G and g.34078 T>G, as well as g.-692 C>T and g.-556 G>T reported in our previous studies, were analyzed. The bulls with H1H12 and H2H2 exhibited a higher ejaculate volume than those with H2H10 and H9H12, respectively (P < 0.05). Bulls with H11H11 and H2H10 exhibited higher initial sperm motility than those with H2H2 (P < 0.05). The expression levels of INCENP in bulls with H1H12 and H11H11 were significantly higher than those in bulls with H9H12 (P < 0.05), as determined by qRT-PCR. Findings suggest that g.19970 A>G and g.34078 T>G in INCENP both of which appear to change the molecular and biological characteristics of the mRNA transcribed from the locus may serve as a biomarkers of male bovine fertility by affecting alternative splicing mode and binding affinity with the target bta-miR-378. PMID:27669152

  5. Correlation Measurement of Lambda-anti-Lambda, Lambda-Lambda and anti-Lambda-anti-Lambda with the ATLAS detector at s=7 TeV

    NASA Astrophysics Data System (ADS)

    Cheng, Hok-Chuen

    This thesis summaries the measurements of correlations between Lambda 0Lambda0, Lambda0Lambda 0, and Lambda0Lambda 0 hyperon pairs produced inclusively at the LHC, which are useful for a better understanding of the quark-antiquark pair production and jet fragmentation and hadronization processes. The analysis is based on hyperon pairs selected using the muon and minimum bias data samples collected at the ATLAS experiment from proton-proton collisions at a center-of-mass energy of 7 TeV in 2010. Excess Lambda0Lambda 0 are observed near the production threshold and are identified to be originated from the parton system in the string model in the MC sample, decaying either directly or through heavy strange resonances such as Sigma0 and Sigma*(1385). Dynamical correlations have been explored through a correlation function defined as the ratio of two-particle to single-particle densities. Positive correlation is observed for Lambda0Lambda0 and anticorrelation is observed for Lambda0Lambda 0 and Lambda0Lambda 0 for Q in [0,2] GeV. The structure replicates similar correlations in pp, pp, and pppp events in PYTHIA generator as predicted by the Lund string fragmentation model. Parameters of the "popcorn" mechanism implemented in the PYTHIA generator are tuned and are found to have little impact on the structure observed. The spin composition of the sample is extracted using a data-driven reference sample built by event mixing. Appropriate corrections have been made to the kinematic distributions in the reference sample by kinematic weighting to make sure that the detector effects are well modeled. A modified Pearson's chi2 test statistics is calculated for the costheta* distribution to determine the best-fitted A-value for data. The results are consistent with zero for both like-type and unlike-type hyperon pairs in Q ∈ [0,10] GeV and Q ∈ [1,10] GeV respectively. The data statistics in the range of Q ∈ [0, 1] GeV is currently too low for the estimation of the emitter size for Fermi-Dirac correlation.

  6. Epidermal growth factor receptor expression in gastric tumors and its relationship with the germline polymorphisms - 216 G>T, -191 C>A, (CA) n IVS1, and R521K.

    PubMed

    Torres-Jasso, J H; Bustos-Carpinteyro, A R; Garcia-Gonzalez, J R; Peregrina-Sandoval, J; Cruz-Ramos, J A; Santiago-Luna, E; Sanchez-Lopez, J Y

    2016-01-01

    Gastric cancer (GC) is the third worldwide leading cause of cancer-related death affecting both sexes. The aberrant expression of epidermal growth factor receptor (EGFR) gene has been detected in many human epithelial malignancies and linked to advanced disease, more aggressive phenotype, and poor prognosis. To analyze the relation that the expression of EGFR in gastric tumors holds with pathological characteristics and with the germline polymorphisms -216 G>T, -191 C>A, (CA) n IVS1, and R521K. We studied 22 biopsies from gastric tumors obtained by endoscopy. EGFR expression was determined by relative quantification real-time polymerase chain reaction with the glyceraldehyde-3-phosphate dehydrogenase reference gene (as for messenger RNA [mRNA]) and by immunohistochemistry (IHC) (as for protein). EGFR germline polymorphisms were analyzed by sequencing, GeneScan, and restriction fragment length polymorphisms. EGFR mRNA expression was increased (>2-fold) in 13.6% of GC cases, decreased (<0.5-fold) in 68.2%, and normal in 18.2%; overexpression was related to well-differentiated gastric tumors, whereas underexpression was linked to moderate or poorly differentiated gastric tumors (P < 0.001). EGFR protein expression was high (IHC 2+ and 3+) in 29.4% of gastric tumors and was normal or low (score 0 to 1+) in 70.6% cases. EGFR expression, in both mRNA and protein, was not related to any EGFR polymorphism (P > 0.05). Most gastric tumors showed low EGFR expression (mRNA and protein), whereas EGFR overexpression was related to well-differentiated gastric tumors. Furthermore, germinal polymorphisms -216, -191, (CA) n IVS1, and R521K were not related to EGFR expression (mRNA or protein).

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

    Akaishi, Yoshinori; College of Science and Technology, Nihon University, Funabashi 274-8501; Myint, Khin Swe

    The overbinding problem of {sub {lambda}}{sup 5}He is solved by introducing a concept of coherent {lambda}-{sigma} coupling which is equivalent to a {lambda}NN three-body force. This three-body force is coherently enhanced in the 0{sup +} states of {sub {lambda}}{sup 4}H and {sub {lambda}}{sup 4}He. The 0{sup +}-1{sup +} splitting in these hypernuclei is mainly due to coherent {lambda}-{sigma} coupling and partly due to the {lambda}N spin-spin interaction. A {lambda}NN three-body potential is derived from the coupled-channel treatment. The origin of the repulsive and attractive nature of the three-body force is discussed. Coherent {lambda}-{sigma} coupling becomes more important in neutron-rich hypernucleimore » and especially in neutron-star matter at high densities. The possible existence of ''hyperheavy hydrogen'', {sub {lambda}}{sup 6}H, is suggested.« less

  8. 46 CFR 11.307 - Requirements to qualify for an STCW endorsement as chief mate of vessels of 3,000 GT or more...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... gained in the engine department on vessels may be creditable for up to 1 month of the service... meteorology. (iv) Leadership and managerial skills. (v) Search and rescue. (vi) ARPA, if serving on a vessel...

  9. 46 CFR 12.05-11 - General provisions respecting merchant mariner's document endorsed for service as able seamen.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... as a rating forming part of a navigational watch (RFPNW) on a seagoing ship of 500 GT or more. (b) An... seaman—on freight vessels, 500 gross tons or less on bays or sounds, and on tugs, towboats, and barges on...

  10. 46 CFR 12.05-11 - General provisions respecting merchant mariner's document endorsed for service as able seamen.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... as a rating forming part of a navigational watch (RFPNW) on a seagoing ship of 500 GT or more. (b) An... seaman—on freight vessels, 500 gross tons or less on bays or sounds, and on tugs, towboats, and barges on...

  11. 46 CFR 12.05-11 - General provisions respecting merchant mariner's document endorsed for service as able seamen.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... as a rating forming part of a navigational watch (RFPNW) on a seagoing ship of 500 GT or more. (b) An... seaman—on freight vessels, 500 gross tons or less on bays or sounds, and on tugs, towboats, and barges on...

  12. 46 CFR 12.05-11 - General provisions respecting merchant mariner's document endorsed for service as able seamen.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... as a rating forming part of a navigational watch (RFPNW) on a seagoing ship of 500 GT or more. (b) An... seaman—on freight vessels, 500 gross tons or less on bays or sounds, and on tugs, towboats, and barges on...

  13. Role of the Escherichia coli grpE heat shock protein in the initiation of bacteriophage lambda DNA replication.

    PubMed

    Osipiuk, J; Zylicz, M

    1991-01-01

    Initiation of replication of lambda DNA requires assembly of the proper nucleoprotein complex consisting of the lambda origin of replication-lambda O-lambda P-dnaB proteins. The dnaJ, dnaK and grpE heat shock proteins destabilize the lambda P-dnaB interaction in this complex permitting dnaB helicase to unwind lambda DNA near ori lambda sequence. First step of this disassembling reaction is the binding of dnaK protein to lambda P protein. In this report we examined the influence of dnaJ and grpE proteins on stability of the lambda P-dnaK complex. Our results show that grpE alone dissociates this complex, but both grpE and dnaJ together do not. These results suggest that, in the presence of grpE protein, dnaK protein has a higher affinity for lambda P protein complexed with dnaJ protein than in the situation where grpE protein is not used.

  14. Evidence for the Confinement of Magnetic Monopoles in Quantum Spin Ice.

    PubMed

    Sarte, Paul Maximo; Aczel, Adam; Ehlers, Georg; Stock, Christopher; Gaulin, Bruce D; Mauws, Cole; Stone, Matthew B; Calder, Stuart; Nagler, Stephen; Hollett, Joshua; Zhou, Haidong; Gardner, Jason S; Attfield, J Paul; Wiebe, Christopher R

    2017-09-25

    Magnetic monopoles are hypothesised elementary particles connected by Dirac strings that behave like infinitely thin solenoids [Dirac 1931 Proc. Roy. Soc. A 133 60]. Despite decades of searches, free magnetic monopoles and their Dirac strings have eluded experimental detection, although there is substantial evidence for deconfined magnetic monopole quasiparticles in spin ice materials [Castelnovo, Moessner & Sondhi 2008 Nature 326 411]. Here we report the detection of a hierarchy of unequally-spaced magnetic excitations via high resolution inelastic neutron spectroscopic measurements on the quantum spin ice candidate Pr<sub>2</sub>Sn<sub>2</sub>O<sub>7</sub>. These excitations are well-described by a simple model of monopole pairs bound by a linear potential [Coldea et al. Science 327 177] with an effective tension of 0.7(1) K/Angstrom. The success of the linear potential model suggests that these low energy magnetic excitations are direct spectroscopic evidence for the confinement of magnetic monopole quasiparticles in the quantum spin ice candidate Pr<sub>2</sub>Sn<sub>2</sub>O<sub>7</sub>. © 2017 IOP Publishing Ltd.

  15. Landau theory for magnetic and structural transitions in CeCo0.85Fe0.15Si.

    PubMed

    Carreras, William Gabriel; Correa, Víctor Félix; Sereni, Julian G; García, Daniel J; Cornaglia, Pablo S

    2018-06-05

    We present a phenomenological analysis of the magnetoelastic properties of CeCo<sub>0.85</sub>Fe<sub>0.15</sub>Si at temperatures close to the Néel transition temperature T<sub>N</sub>. Using a Landau functional we provide a qualitative description of the thermal expansion, magnetostriction, magnetization and specific heat data. We show that the available experimental results [Journal of Physics: Condensed Matter <b>28</b> 346003 (2016)] are consistent with the presence of a structural transition at T<sub>s</sub>≧ T<sub>N</sub> and a strong magnetoelastic coupling. The magnetoelastic coupling presents a Janus-faced effect: while the structural transition is shifted to higher temperatures as the magnetic field is increased, the resulting striction at low temperatures decreases. The strong magnetoelastic coupling and the proximity of the structural transition to the onset temperature for magnetic fluctuations, suggest that the transition could be an analogue of the tetragonal to orthorhombic observed in Fe-based pcnictides. . © 2018 IOP Publishing Ltd.

  16. Expression of Interferon Lambda 4 Is Associated with Reduced Proliferation and Increased Cell Death in Human Hepatic Cells

    PubMed Central

    Onabajo, Olusegun O.; Porter-Gill, Patricia; Paquin, Ashley; Rao, Nina; Liu, Luyang; Tang, Wei; Brand, Nathan

    2015-01-01

    Interferon lambda 4 (IFN-λ4) is a novel type-III interferon that can be generated only in individuals carrying a ΔG frame-shift allele of an exonic genetic variant (rs368234815-ΔG/TT). The rs368234815-ΔG allele is strongly associated with decreased clearance of hepatitis C virus (HCV) infection. Here, we further explored the biological function of IFN-λ4 expressed in human hepatic cells—a hepatoma cell line HepG2 and fresh primary human hepatocytes (PHHs). We performed live confocal imaging, cell death and proliferation assays, mRNA expression profiling, protein detection, and antibody blocking assays using transient and inducible stable in vitro systems. Not only did we observe significant intracellular retention of IFN-λ4 but also detected secreted IFN-λ4 in the culture media of expressing cells. Secreted IFN-λ4 induced strong activation of the interferon-stimulated genes (ISGs) in IFN-λ4-expressing and surrounding cells in transwell assays. Specifically, in PHHs, secreted IFN-λ4 induced expression of the CXCL10 transcript and a corresponding pro-inflammatory chemokine, IP-10. In IFN-λ4-expressing HepG2 cells, we also observed decreased proliferation and increased cell death. All IFN-λ4-induced phenotypes—activation of ISGs, decreased proliferation, and increased cell death—could be inhibited by an anti-IFN-λ4-specific antibody. Our study offers new insights into biology of IFN-λ4 and its possible role in HCV clearance. PMID:26134097

  17. Using Grounded Theory Method to Capture and Analyze Health Care Experiences.

    PubMed

    Foley, Geraldine; Timonen, Virpi

    2015-08-01

    Grounded theory (GT) is an established qualitative research method, but few papers have encapsulated the benefits, limits, and basic tenets of doing GT research on user and provider experiences of health care services. GT can be used to guide the entire study method, or it can be applied at the data analysis stage only. We summarize key components of GT and common GT procedures used by qualitative researchers in health care research. We draw on our experience of conducting a GT study on amyotrophic lateral sclerosis patients' experiences of health care services. We discuss why some approaches in GT research may work better than others, particularly when the focus of study is hard-to-reach population groups. We highlight the flexibility of procedures in GT to build theory about how people engage with health care services. GT enables researchers to capture and understand health care experiences. GT methods are particularly valuable when the topic of interest has not previously been studied. GT can be applied to bring structure and rigor to the analysis of qualitative data. © Health Research and Educational Trust.

  18. Using Grounded Theory Method to Capture and Analyze Health Care Experiences

    PubMed Central

    Foley, Geraldine; Timonen, Virpi

    2015-01-01

    Objective Grounded theory (GT) is an established qualitative research method, but few papers have encapsulated the benefits, limits, and basic tenets of doing GT research on user and provider experiences of health care services. GT can be used to guide the entire study method, or it can be applied at the data analysis stage only. Methods We summarize key components of GT and common GT procedures used by qualitative researchers in health care research. We draw on our experience of conducting a GT study on amyotrophic lateral sclerosis patients’ experiences of health care services. Findings We discuss why some approaches in GT research may work better than others, particularly when the focus of study is hard-to-reach population groups. We highlight the flexibility of procedures in GT to build theory about how people engage with health care services. Conclusion GT enables researchers to capture and understand health care experiences. GT methods are particularly valuable when the topic of interest has not previously been studied. GT can be applied to bring structure and rigor to the analysis of qualitative data. PMID:25523315

  19. Stable carbon isotope fractionation during the biodegradation of lambda-cyhalothrin.

    PubMed

    Shen, Xiaoli; Xu, Zemin; Zhang, Xichang; Yang, Fangxing

    2015-11-01

    In this study, the microbial degradation of lambda-cyhalothrin in soil was investigated using compound-specific stable isotope analysis. The results revealed that lambda-cyhalothrin was biodegraded in soil under laboratory conditions. The half-lives of lambda-cyhalothrin were determined to be 49 and 161 days in non-sterile and sterile soils spiked with 2mg/kg lambda-cyhalothrin and 84 and 154 days in non-sterile and sterile soils spiked with 10mg/kg lambda-cyhalothrin, respectively. The biodegradation of lambda-cyhalothrin resulted in carbon isotope fractionation, which shifted from -29.0‰ to -26.5‰ in soil spiked with 2mg/kg lambda-cyhalothrin, and to -27.5‰ with 10mg/kg lambda-cyhalothrin. A relationship was established between the stable carbon isotope fraction and the residual concentrations of lambda-cyhalothrin by the Rayleigh equation in which the carbon isotope enrichment factor ε of the microbial degradation of lambda-cyhalothrin in the soil was calculated as -2.53‰. This study provides an approach to quantitatively evaluate the biodegradation of lambda-cyhalothrin in soil in field studies. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Dynamics of a family of transcendental meromorphic functions having rational Schwarzian derivative

    NASA Astrophysics Data System (ADS)

    Sajid, M.; Kapoor, G. P.

    2007-02-01

    In the present paper, a class of critically finite transcendental meromorphic functions having rational Schwarzian derivative is introduced and the dynamics of functions in one parameter family is investigated. It is found that there exist two parameter values [lambda]*=[phi](0)>0 and , where and is the real root of [phi]'(x)=0, such that the Fatou sets of f[lambda](z) for [lambda]=[lambda]* and [lambda]=[lambda]** contain parabolic domains. A computationally useful characterization of the Julia set of the function f[lambda](z) as the complement of the basin of attraction of an attracting real fixed point of f[lambda](z) is established and applied for the generation of the images of the Julia sets of f[lambda](z). Further, it is observed that the Julia set of explodes to whole complex plane for [lambda]>[lambda]**. Finally, our results found in the present paper are compared with the recent results on dynamics of one parameter families [lambda]tanz, [R.L. Devaney, L. Keen, Dynamics of meromorphic maps: Maps with polynomial Schwarzian derivative, Ann. Sci. Ecole Norm. Sup. 22 (4) (1989) 55-79; L. Keen, J. Kotus, Dynamics of the family [lambda]tan(z), Conform. Geom. Dynam. 1 (1997) 28-57; G.M. Stallard, The Hausdorff dimension of Julia sets of meromorphic functions, J. London Math. Soc. 49 (1994) 281-295] and , [lambda]>0 [G.P. Kapoor, M. Guru Prem Prasad, Dynamics of : The Julia set and bifurcation, Ergodic Theory Dynam. Systems 18 (1998) 1363-1383].

  1. Thyroid hormone signalling is altered in response to physical training in patients with end-stage heart failure and mechanical assist devices: potential physiological consequences?

    PubMed

    Adamopoulos, Stamatios; Gouziouta, Aggeliki; Mantzouratou, Polixeni; Laoutaris, Ioannis D; Dritsas, Athanasios; Cokkinos, Dennis V; Mourouzis, Iordanis; Sfyrakis, Petros; Iervasi, Giorgio; Pantos, Constantinos

    2013-10-01

    The present study investigated the potential of the failing myocardium of patients with ventricular assist devices (VAD) to respond to physiological growth stimuli, such as exercise, by activating growth signalling pathways. This may be of therapeutic relevance in identifying novel pharmacological targets for therapies that could facilitate recovery after VAD implantation. Twenty-two patients bridged to heart transplantation (HTx) with VAD were included in the study. A group of patients underwent moderate intensity aerobic exercise (GT), while another group of patients did not receive exercise training (CG). Thyroid hormone receptor alpha1 (TRα1) protein and total (t) and phosphorylated (p) protein kinase B (Akt) and c-Jun N-terminal kinase (JNK) kinase signalling were measured in myocardial tissue by western blotting at pre-VAD and pre-HTx period. In addition, Thyroid hormone (TH) levels were measured in plasma. Peak oxygen consumption (VO2) at pre-HTx period was higher in patients subjected to training protocol [18.0 (0.8) for GT when compared with 13.7 (0.7) for CG group, P = 0.002]. N-terminal-prohormone of brain natriuretic peptide (NT-proBNP) levels were 1068 (148) for CG vs 626 (115) for GT group, P = 0.035. A switch towards up-regulation of physiological growth signalling was observed: the ratio of p-Akt/t-Akt was 2-fold higher in GT vs CG, P < 0.05 while p-JNK/t-JNK was 2.5-fold lower (P < 0.05) in GT vs CG, in pre-HTx samples. This response was accompanied by a 2.0-fold increase in TRα1 expression in pre-HTx samples with concomitant increase in circulating T3 in GT vs CG, P < 0.05. No differences in peak VO2, NT-proBNP, T3, TRα1, p/t-AKT and p/t-JNK were found between groups in the pre-VAD period. The unloaded failing myocardium responded to physical training by enhancing thyroid hormone signalling. This response was associated with an up-regulation of Akt and suppression of JNK activation.

  2. A carbon accumulation maximum during the Medieval Climate Anomaly in the world’s biggest bog, Siberia

    NASA Astrophysics Data System (ADS)

    Beilman, D.; MacDonald, G. M.

    2009-12-01

    The West Siberia Lowland is the most carbon-rich northern wetland region, holding an important portion of total northern peatland carbon (70 Gt of 270-450 Gt C) mainly in the southern lowland (44 Gt) in very large peatlands. The largest of these, the Great Vasyugan Bog complex, spans 63,252 km2 and alone holds ~11 Gt C. Our previous work has shown that recent-past growth of WSL peat C pool has been greatest in southern WSL in large peatlands close to the southern limit of peatland distribution. In this study, we investigate a Great Vasyugan site to investigate peat carbon sensitivity in two ways: 1) assess past changes in vegetation, species-specific 13C geochemistry, and rate of carbon accumulation relative to recent-past climate variation, and 2) assess the relative lability of this deep peat C through laboratory incubations. Carbon accumulation over the last 2000 years, a period of relatively consistent vegetation and litter inputs but variable local hydrology, reached a maximum between 1150 and 1350 AD during Medieval Climate Anomaly conditions. A carbon accumulation minimum occurred between about 1350 and 1550 AD. Regardless of depth, age, or rate of carbon burial, deep peat from between 30 and 230 cm below the surface showed a similar rate of potential aerobic respiration that changed little over 42 days of incubation. Taken together, these data suggest that in some peatlanlds warmer and hydrologically-variable conditions can promote long-term belowground carbon storage.

  3. Trends in use of genotypic resistance testing and frequency of major drug resistance among antiretroviral-naive persons in the HIV Outpatient Study, 1999-2011.

    PubMed

    Buchacz, Kate; Young, Benjamin; Palella, Frank J; Armon, Carl; Brooks, John T

    2015-08-01

    Monitoring antiretroviral drug resistance can inform treatment recommendations; however, there are few such data from US patients before they initiate ART. We analysed data from HIV Outpatient Study (HOPS) participants from nine US HIV clinics who were diagnosed with HIV infection during 1999-2011. Using the IAS-USA December 2010 guidelines, we assessed the frequency of major drug resistance mutations (mDRMs) related to antiretroviral agents in viral isolates from patients who underwent commercial genotypic testing (GT) for resistance before initiating ART. We employed general linear regression models to assess factors associated with having undergone GT, and then factors associated with having mDRM. Among 1531 eligible patients, 758 (49.5%) underwent GT before first ART, increasing from 15.5% in 1999-2002 to 75.9% in 2009-11 (P < 0.001). GT was carried out a median of 1.2 months after the diagnosis of HIV. In adjusted regression analyses, patients with pre-ART CD4+ T lymphocyte counts ≥200 cells/mm(3) or with HIV RNA levels >5.0 log10 copies/mL and those with a first HOPS visit in 2006 or later were significantly (P < 0.05) more likely to have undergone GT. Of the 758 patients, 114 (15.0%) had mDRMs; mutations relating to NRTIs, NNRTIs and PIs were present in 8.0%, 7.1% and 2.6%, respectively. There was no temporal change in the frequency of mDRM, and mDRMs were associated with an HIV RNA level <4.0 log10 copies/mL. During 1999-2011, GT use among antiretroviral-naive patients became more common, but a quarter of patients in recent years remained untested. The frequency of mDRMs remained stable over time at about 15%. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  4. Immunological comparison of sulfite oxidase

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

    Pollock, V.; Barber, M.J.

    1991-03-11

    Polyclonal antibodies (rabbit), elicited against FPLC-purified chicken and rat liver sulfite oxidase (SO), have been examined for inhibition and binding to purified chicken (C), rat (R), bovine (B), alligator (A) and shark (S) liver enzymes. Anti-CSO IgG cross-reacted with all five enzymes, with varying affinities, in the order CSO=ASO{gt}RSO{gt}BSO{gt}SSO. Anti-ROS IgG also cross-reacted with all five enzymes in the order RSO{gt}CSO=ASO{gt}BSO{gt}SSO. Anti-CSO IgG inhibited sulfite:cyt. c reductase (S:CR), sulfite:ferricyanide reductase (S:FR) and sulfite:dichlorophenolindophenol reductase (S:DR) activities of CSO to different extents (S:CR{gt}S:FR=S:DR). Similar differential inhibition was found for anti-ROS IgG and RSO S:CR, S:FR and S:DR activities. Anti-CSO IgG inhibitedmore » S:CR activities in the order CSO=ASO{much gt}SSO{gt}BSO. RSO was uninhibited. For anti-RSO IgG the inhibition order was RSO{gt}SSO{gt}BSO{gt}ASO. CSO was uninhibited. Anti-CSO and RSO IgGs partially inhibited Chlorella nitrate reductase (NR). Minor cross-reactivity was found for xanthine oxidase. Common antigenic determinants for all five SO's and NR are indicated.« less

  5. Jovian Chromophore Characteristics from Multispectral HST Images

    NASA Technical Reports Server (NTRS)

    Strycker, Paul D.; Chanover, Nancy J.; Simon-Miller, Amy A.; Banfield, Don; Gierasch, Peter J.

    2011-01-01

    The chromophores responsible for coloring the jovian atmosphere are embedded within Jupiter's vertical aerosol structure. Sunlight propagates through this vertical distribution of aerosol particles, whose colors are defined by omega-bar (sub 0)(lambda), and we remotely observe the culmination of the radiative transfer as I/F(lambda). In this study, we employed a radiative transfer code to retrieve omega-bar (sub 0)(lambda) for particles in Jupiter's tropospheric haze at seven wavelengths in the near-UV and visible regimes. The data consisted of images of the 2008 passage of Oval BA to the south of the Great Red Spot obtained by the Wide Field Planetary Camera 2 on-board the Hubble Space Telescope. We present derived particle colors for locations that were selected from 14 weather regions, which spanned a large range of observed colors. All omega-bar (sub 0)(lambda) curves were absorbing in the blue, and omega-bar (sub 0)(lambda) increased monotonically to approximately unity as wavelength increased. We found accurate fits to all omega-bar (sub 0)(lambda) curves using an empirically derived functional form: omega-bar (sub 0)(lambda) = 1 A exp(-B lambda). The best-fit parameters for the mean omega-bar (sub 0)(lambda) curve were A = 25.4 and B = 0.0149 for lambda in units of nm. We performed a principal component analysis (PCA) on our omega-bar (sub 0)(lambda) results and found that one or two independent chromophores were sufficient to produce the variations in omega-bar (sub 0)(lambda). A PCA of I/F(lambda) for the same jovian locations resulted in principal components (PCs) with roughly the same variances as the omega-bar (sub 0)(lambda) PCA, but they did not result in a one-to-one mapping of PC amplitudes between the omega-bar (sub 0)(lambda) PCA and I/F(lambda) PCA. We suggest that statistical analyses performed on I/ F(lambda) image cubes have limited applicability to the characterization of chromophores in the jovian atmosphere due to the sensitivity of 1/ F(lambda) to horizontal variations in the vertical aerosol distribution.

  6. Mechanisms of Hyperbilirubinemia During Peginterferon Lambda-1a Therapy for Chronic Hepatitis C Infection: A Retrospective Investigation.

    PubMed

    Zwirtes, Ricardo; Narasimhan, Premkumar; Wind-Rotolo, Megan M; Xu, Dong; Hruska, Matthew W; Kishnani, Narendra; Colston, Elizabeth M; Srinivasan, Subasree

    2016-11-01

    The phase 2b EMERGE study compared the efficacy/safety of peginterferon lambda-1a (Lambda) and peginterferon alfa-2a (Alfa), both with ribavirin (RBV), for treatment of chronic hepatitis C virus (HCV) infection. A key safety finding was a higher frequency of hyperbilirubinemia with Lambda/RBV versus Alfa/RBV. To characterize mechanisms of hyperbilirubinemia associated with Lambda/RBV, we conducted a retrospective analysis of safety data from the HCV genotype 1 and genotype 4 cohort of the EMERGE study. Subjects were randomized to once-weekly Lambda (120/180/240 μg) or Alfa (180 μg), with daily RBV, for 48 weeks. Early-onset Lambda/RBV-related hyperbilirubinemia events (6-12 weeks) resulted mostly from RBV-induced hemolysis evidenced by sustained reticulocytosis and a predominantly unconjugated pattern of hyperbilirubinemia. The higher hyperbilirubinemia frequency with Lambda/RBV versus Alfa/RBV was attributed to bone marrow suppression known to occur with Alfa but not Lambda. Late-onset (>12 weeks) Lambda/RBV-related hyperbilirubinemia events occurred most frequently with higher Lambda doses and were associated with increased levels of hepatic transaminase and direct bilirubin fractions compared with early events. This dual pattern of hyperbilirubinemia observed while on Lambda/RBV treatment is thought to be caused by exaggerated RBV-induced hemolysis in early-onset events compared with possible direct Lambda-induced hepatocellular toxicity in late-onset events.

  7. Existence and non-uniqueness of similarity solutions of a boundary-layer problem

    NASA Technical Reports Server (NTRS)

    Hussaini, M. Y.; Lakin, W. D.

    1986-01-01

    A Blasius boundary value problem with inhomogeneous lower boundary conditions f(0) = 0 and f'(0) = - lambda with lambda strictly positive was considered. The Crocco variable formulation of this problem has a key term which changes sign in the interval of interest. It is shown that solutions of the boundary value problem do not exist for values of lambda larger than a positive critical value lambda. The existence of solutions is proven for 0 lambda lambda by considering an equivalent initial value problem. It is found however that for 0 lambda lambda, solutions of the boundary value problem are nonunique. Physically, this nonuniqueness is related to multiple values of the skin friction.

  8. Existence and non-uniqueness of similarity solutions of a boundary layer problem

    NASA Technical Reports Server (NTRS)

    Hussaini, M. Y.; Lakin, W. D.

    1984-01-01

    A Blasius boundary value problem with inhomogeneous lower boundary conditions f(0) = 0 and f'(0) = - lambda with lambda strictly positive was considered. The Crocco variable formulation of this problem has a key term which changes sign in the interval of interest. It is shown that solutions of the boundary value problem do not exist for values of lambda larger than a positive critical value lambda. The existence of solutions is proven for 0 lambda lambda by considering an equivalent initial value problem. It is found however that for 0 lambda lambda, solutions of the boundary value problem are nonunique. Physically, this nonuniqueness is related to multiple values of the skin friction.

  9. Measurement of the Lambda b0 lifetime in Lambda b0-->J/psi Lambda 0 in pp collisions at square root s=1.96 TeV.

    PubMed

    Abulencia, A; Adelman, J; Affolder, T; Akimoto, T; Albrow, M G; Ambrose, D; Amerio, S; Amidei, D; Anastassov, A; Anikeev, K; Annovi, A; Antos, J; Aoki, M; Apollinari, G; Arguin, J-F; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Azfar, F; Azzi-Bacchetta, P; Azzurri, P; Bacchetta, N; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Baroiant, S; Bartsch, V; Bauer, G; Bedeschi, F; Behari, S; Belforte, S; Bellettini, G; Bellinger, J; Belloni, A; Benjamin, D; Beretvas, A; Beringer, J; Berry, T; Bhatti, A; Binkley, M; Bisello, D; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bolshov, A; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Budroni, S; Burkett, K; Busetto, G; Bussey, P; Byrum, K L; Cabrera, S; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carrillo, S; Carlsmith, D; Carosi, R; Carron, S; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, I; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Ciljak, M; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Coca, M; Compostella, G; Convery, M E; Conway, J; Cooper, B; Copic, K; Cordelli, M; Cortiana, G; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; Cyr, D; DaRonco, S; D'Auria, S; Davies, T; D'Onofrio, M; Dagenhart, D; de Barbaro, P; De Cecco, S; Deisher, A; De Lentdecker, G; Dell'Orso, M; Delli Paoli, F; Demortier, L; Deng, J; Deninno, M; De Pedis, D; Derwent, P F; Di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; DiTuro, P; Dörr, C; Donati, S; Donega, M; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, I; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Field, R; Flanagan, G; Foland, A; Forrester, S; Foster, G W; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garcia, J E; Garberson, F; Garfinkel, A F; Gay, C; Gerberich, H; Gerdes, D; Giagu, S; Giannetti, P; Gibson, A; Gibson, K; Gimmell, J L; Ginsburg, C; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Goldstein, J; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Griffiths, M; Grinstein, S; Grosso-Pilcher, C; Group, R C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Hamilton, A; Han, B-Y; Han, J Y; Handler, R; Happacher, F; Hara, K; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hauser, J; Heijboer, A; Heinemann, B; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Holloway, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ishizawa, Y; Ivanov, A; Iyutin, B; James, E; Jang, D; Jayatilaka, B; Jeans, D; Jensen, H; Jeon, E J; Jindariani, S; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Karchin, P E; Kato, Y; Kemp, Y; Kephart, R; Kerzel, U; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Klute, M; Knuteson, B; Ko, B R; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kovalev, A; Kraan, A C; Kraus, J; Kravchenko, I; Kreps, M; Kroll, J; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhlmann, S E; Kuhr, T; Kusakabe, Y; Kwang, S; Laasanen, A T; Labarga, L; Lai, S; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; LeCompte, T; Lee, J; Lee, J; Lee, Y J; Lee, S W; Lefèvre, R; Leonardo, N; Leone, S; Levy, S; Lewis, J D; Lin, C; Lin, C S; Lindgren, M; Lipeles, E; Liss, T M; Lister, A; Litvintsev, D O; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Loverre, P; Lu, R-S; Lucchesi, D; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Lytken, E; Mack, P; MacQueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Manca, G; Margaroli, F; Marginean, R; Marino, C; Marino, C P; Martin, A; Martin, M; Martin, V; Martínez, M; Maruyama, T; Mastrandrea, P; Masubuchi, T; Matsunaga, H; Mattson, M E; Mazini, R; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzemer, S; Menzione, A; Merkel, P; Mesropian, C; Messina, A; Miao, T; Miladinovic, N; Miles, J; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyamoto, A; Moed, S; Moggi, N; Mohr, B; Moore, R; Morello, M; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Nachtman, J; Nagano, A; Naganoma, J; Nahn, S; Nakano, I; Napier, A; Necula, V; Neu, C; Neubauer, M S; Nielsen, J; Nigmanov, T; Nodulman, L; Norniella, O; Nurse, E; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Oldeman, R; Orava, R; Osterberg, K; Pagliarone, C; Palencia, E; Papadimitriou, V; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Piedra, J; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Portell, X; Poukhov, O; Pounder, N; Prokoshin, F; Pronko, A; Proudfoot, J; Ptochos, F; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ranjan, N; Rappoccio, S; Reisert, B; Rekovic, V; Renton, P; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Ruiz, A; Russ, J; Rusu, V; Saarikko, H; Sabik, S; Safonov, A; Sakumoto, W K; Salamanna, G; Saltó, O; Saltzberg, D; Sánchez, C; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savard, P; Savoy-Navarro, A; Scheidle, T; Schlabach, P; Schmidt, E E; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scott, A L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sfyrla, A; Shapiro, M D; Shears, T; Shepard, P F; Sherman, D; Shimojima, M; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Sjolin, J; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soderberg, M; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spinella, F; Spreitzer, T; Squillacioti, P; Stanitzki, M; Staveris-Polykalas, A; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Stuart, D; Suh, J S; Sukhanov, A; Sun, H; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Takikawa, K; Tanaka, M; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Tesarek, R J; Thom, J; Thompson, A S; Thomson, E; Tipton, P; Tiwari, V; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Tourneur, S; Trischuk, W; Tsuchiya, R; Tsuno, S; Turini, N; Ukegawa, F; Unverhau, T; Uozumi, S; Usynin, D; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Veramendi, G; Veszpremi, V; Vidal, R; Vila, I; Vilar, R; Vine, T; Vollrath, I; Volobouev, I; Volpi, G; Würthwein, F; Wagner, P; Wagner, R G; Wagner, R L; Wagner, J; Wagner, W; Wallny, R; Wang, S M; Warburton, A; Waschke, S; Waters, D; Weinberger, M; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Wynne, S M; Yagil, A; Yamamoto, K; Yamaoka, J; Yamashita, T; Yang, C; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zaw, I; Zhang, X; Zhou, J; Zucchelli, S

    2007-03-23

    We report a measurement of the Lambda b0 lifetime in the exclusive decay Lambda b0-->J/psi Lambda 0 in pp collisions at square root s=1.96 TeV using an integrated luminosity of 1.0 fb-1 of data collected by the CDF II detector at the Fermilab Tevatron. Using fully reconstructed decays, we measure tau(Lambda b0)=1.593(-0.078)(+0.083)(stat)+/-0.033(syst) ps. This is the single most precise measurement of tau(Lambda b0) and is 3.2sigma higher than the current world average.

  10. Presence of rare hepatitis C virus subtypes, 2j, 2k, and 2r in Mexico City as identified by sequencing.

    PubMed

    Uribe-Noguez, Luis Antonio; Ocaña-Mondragón, Alicia; Mata-Marín, José Antonio; Gómez-Torres, María Elena; Ribas-Aparicio, Rosa María; Martínez-Rodríguez, María de la Luz

    2018-03-06

    The HCV 5'UTR, Core/E1, and NS5B regions of samples from fifty patients infected with the hepatitis C virus (HCV) were analyzed. Seventeen patients were identified with genotype (GT) 1b, eleven with GT-1a, nine with GT-2b and four with GT-3a. Two rare subtypes were detected: GT-2j in two patients and GT-2r in one patient. Three patients had mixed infections: one with GT-2k + 2j and two with GT-1b + 2b. This work identifies HCV GTs, 2j, 2k, and 2r for the first time in Mexico. © 2018 Wiley Periodicals, Inc.

  11. Observation of the baryonic B decay B{sup 0}{yields}{Lambda}{sub c}{sup +}{Lambda}K{sup -}

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

    Lees, J. P.; Poireau, V.; Tisserand, V.

    2011-10-01

    We report the observation of the baryonic B decay B{sup 0}{yields}{Lambda}{sub c}{sup +}{Lambda}K{sup -} with a significance larger than 7 standard deviations based on 471x10{sup 6} BB pairs collected with the BABAR detector at the PEP-II storage ring at SLAC. We measure the branching fraction for the decay B{sup 0}{yields}{Lambda}{sub c}{sup +}{Lambda}K{sup -} to be (3.8{+-}0.8{sub stat}{+-}0.2{sub sys}{+-}1.0{sub {Lambda}}{sub c}{sup +})x10{sup -5}. The uncertainties are statistical, systematic, and due to the uncertainty in the {Lambda}{sub c}{sup +} branching fraction. We find that the {Lambda}{sub c}{sup +}K{sup -} invariant-mass distribution shows an enhancement above 3.5 GeV/c{sup 2}.

  12. Search for lepton flavour violating decays of heavy resonances and quantum black holes to an eμ pair in proton-proton collisions at √s = 8 TeV

    DOE PAGES

    Khachatryan, Vardan

    2016-06-10

    A search for narrow resonances decaying to an electron and a muon is presented. Themore » $$\\mathrm {e}$$ $${\\mu }$$ mass spectrum is also investigated for non-resonant contributions from the production of quantum black holes (QBHs). The analysis is performed using data corresponding to an integrated luminosity of 19.7 $$~\\text {fb}^\\text {-1}$$ collected in proton-proton collisions at a centre-of-mass energy of 8 $$~\\text {TeV}$$ with the CMS detector at the LHC. With no evidence for physics beyond the standard model in the invariant mass spectrum of selected $$\\mathrm {e}\\mu $$ pairs, upper limits are set at 95  $$\\%$$ confidence level on the product of cross section and branching fraction for signals arising in theories with charged lepton flavour violation. In the search for narrow resonances, the resonant production of a $$\\mathrm {\\tau }$$ sneutrino in R-parity violating supersymmetry is considered. The $$\\mathrm {\\tau }$$ sneutrino is excluded for masses below 1.28 $$~\\text {TeV}$$ for couplings $$\\lambda _{132}=\\lambda _{231}=\\lambda '_{311}=0.01$$ , and below 2.30 $$~\\text {TeV}$$ for $$\\lambda _{132}=\\lambda _{231}=0.07$$ and $$\\lambda '_{311}=0.11$$ . These are the most stringent limits to date from direct searches at high-energy colliders. In addition, the resonance searches are interpreted in terms of a model with heavy partners of the $${\\mathrm {Z}} $$ boson and the photon. In a framework of TeV-scale quantum gravity based on a renormalization of Newton’s constant, the search for non-resonant contributions to the $$\\mathrm {e}$$ $${\\mu }$$ mass spectrum excludes QBH production below a threshold mass $$M_{\\mathrm {th}}$$ of 1.99 $$~\\text {TeV}$$ . In models that invoke extra dimensions, the bounds range from 2.36 $$~\\text {TeV}$$ for one extra dimension to 3.63 $$~\\text {TeV}$$ for six extra dimensions. Furthermore, this is the first search for QBHs decaying into the $$\\mathrm {e}$$ $${\\mu }$$ final state.« less

  13. Hybrid Sequencing of Full-Length cDNA Transcripts of Stems and Leaves in Dendrobium officinale

    PubMed Central

    He, Liu; Fu, Shuhua; Xu, Zhichao; Yan, Jun; Xu, Jiang; Zhou, Hong; Zhou, Jianguo; Chen, Xinlian; Li, Ying; Au, Kin Fai; Yao, Hui

    2017-01-01

    Dendrobium officinale is an extremely valuable orchid used in traditional Chinese medicine, so sought after that it has a higher market value than gold. Although the expression profiles of some genes involved in the polysaccharide synthesis have previously been investigated, little research has been carried out on their alternatively spliced isoforms in D. officinale. In addition, information regarding the translocation of sugars from leaves to stems in D. officinale also remains limited. We analyzed the polysaccharide content of D. officinale leaves and stems, and completed in-depth transcriptome sequencing of these two diverse tissue types using second-generation sequencing (SGS) and single-molecule real-time (SMRT) sequencing technology. The results of this study yielded a digital inventory of gene and mRNA isoform expressions. A comparative analysis of both transcriptomes uncovered a total of 1414 differentially expressed genes, including 844 that were up-regulated and 570 that were down-regulated in stems. Of these genes, one sugars will eventually be exported transporter (SWEET) and one sucrose transporter (SUT) are expressed to a greater extent in D. officinale stems than in leaves. Two glycosyltransferase (GT) and four cellulose synthase (Ces) genes undergo a distinct degree of alternative splicing. In the stems, the content of polysaccharides is twice as much as that in the leaves. The differentially expressed GT and transcription factor (TF) genes will be the focus of further study. The genes DoSWEET4 and DoSUT1 are significantly expressed in the stem, and are likely to be involved in sugar loading in the phloem. PMID:28981454

  14. Doublet-spacing enhancement caused by {Lambda}N-{Sigma}N coupling in {sub {Lambda}L}i hypernuclear isotopes

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

    Umeya, Atsushi; Harada, Toru; Research Center for Physics and Mathematics, Osaka Electro-Communication University, Neyagawa, Osaka 572-8530

    2011-03-15

    We theoretically investigate energy spacings of doublets in {sub {Lambda}L}i hypernuclear isotopes with A=7-10 in shell-model calculations with a {Lambda}N-{Sigma}N coupling effect. The calculated results show that the energy shifts are {Delta}{epsilon}=0.09-0.28 MeV and the {Sigma}-mixing probabilities are P{sub {Sigma}}=0.10%-0.34% in {Lambda} ground states for the isotopes because of the {Lambda}N-{Sigma}N coupling in the first-order perturbation. It is found that the energy spacing of the doublet is enhanced as a neutron number N increases; the contribution of the {Lambda}N-{Sigma}N coupling interaction is comparable to that of the {Lambda}N interaction in the neutron-rich {Lambda} hypernuclei. The coherent mechanism of this doublet-spacingmore » enhancement is also discussed in terms of Fermi-type and Gamow-Teller-type {Lambda}N-{Sigma}N couplings.« less

  15. The role of template superhelicity in the initiation of bacteriophage lambda DNA replication.

    PubMed Central

    Alfano, C; McMacken, R

    1988-01-01

    The prepriming steps in the initiation of bacteriophage lambda DNA replication depend on the action of the lambda O and P proteins and on the DnaB helicase, single-stranded DNA binding protein (SSB), and DnaJ and DnaK heat shock proteins of the E. coli host. The binding of multiple copies of the lambda O protein to the phage replication origin (ori lambda) initiates the ordered assembly of a series of nucleoprotein structures that form at ori lambda prior to DNA unwinding, priming and DNA synthesis steps. Since the initiation of lambda DNA replication is known to occur only on supercoiled templates in vivo and in vitro, we examined how the early steps in lambda DNA replication are influenced by superhelical tension. All initiation complexes formed prior to helicase-mediated DNA-unwinding form with high efficiency on relaxed ori lambda DNA. Nonetheless, the DNA templates in these structures must be negatively supertwisted before they can be replicated. Once DNA helicase unwinding is initiated at ori lambda, however, later steps in lambda DNA replication proceed efficiently in the absence of superhelical tension. We conclude that supercoiling is required during the initiation of lambda DNA replication to facilitate entry of a DNA helicase, presumably the DnaB protein, between the DNA strands. Images PMID:2847118

  16. Structural, mutagenic and in silico studies of xyloglucan fucosylation in Arabidopsis thaliana suggest a water-mediated mechanism

    DOE PAGES

    Urbanowicz, Breeanna R.; Bharadwaj, Vivek S.; Alahuhta, Markus; ...

    2017-07-03

    The mechanistic underpinnings of the complex process of plant polysaccharide biosynthesis are poorly understood, largely due to the resistance of glycosyltransferase (GT) enzymes to structural characterization. In Arabidopsis thaliana, a glycosyl transferase family 37 (GT37) fucosyltransferase-1 (AtFUT1) catalyzes the regiospecific transfer of terminal 1,2-fucosyl residues to xyloglucan side chains - a key step in the biosynthesis of fucosylated sidechains of galactoxyloglucan. We unravel the mechanistic basis for fucosylation by AtFUT1 with a multipronged approach involving protein expression, X-ray crystallography, mutagenesis experiments and molecular simulations. Mammalian cell culture expressions enable sufficient production of the enzyme for X-ray crystallography, which reveals themore » structural architecture of AtFUT1 in complex with bound donor and acceptor substrate analogs. Here, the lack of an appropriately positioned active site residue as a catalytic base leads us to propose an atypical water-mediated fucosylation mechanism facilitated by an H-bonded network, which is corroborated by mutagenesis experiments as well as detailed atomistic simulations.« less

  17. Structural, mutagenic and in silico studies of xyloglucan fucosylation in Arabidopsis thaliana suggest a water-mediated mechanism

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

    Urbanowicz, Breeanna R.; Bharadwaj, Vivek S.; Alahuhta, Markus

    The mechanistic underpinnings of the complex process of plant polysaccharide biosynthesis are poorly understood, largely due to the resistance of glycosyltransferase (GT) enzymes to structural characterization. In Arabidopsis thaliana, a glycosyl transferase family 37 (GT37) fucosyltransferase-1 (AtFUT1) catalyzes the regiospecific transfer of terminal 1,2-fucosyl residues to xyloglucan side chains - a key step in the biosynthesis of fucosylated sidechains of galactoxyloglucan. We unravel the mechanistic basis for fucosylation by AtFUT1 with a multipronged approach involving protein expression, X-ray crystallography, mutagenesis experiments and molecular simulations. Mammalian cell culture expressions enable sufficient production of the enzyme for X-ray crystallography, which reveals themore » structural architecture of AtFUT1 in complex with bound donor and acceptor substrate analogs. Here, the lack of an appropriately positioned active site residue as a catalytic base leads us to propose an atypical water-mediated fucosylation mechanism facilitated by an H-bonded network, which is corroborated by mutagenesis experiments as well as detailed atomistic simulations.« less

  18. PRESS CONFERENCE - GEMINI-TITAN (GT)-11 - MSC

    NASA Image and Video Library

    1966-08-01

    S66-39895 (1 Aug. 1966) --- Panel members of the Gemini-10 news conference held in the Building 1 auditorium were (from left) Dr. Robert C. Seamans Jr., NASA Deputy Administrator; astronaut John W. Young, Gemini-10 command pilot; astronaut Michael Collins, Gemini-10 pilot; and Dr. Robert R. Gilruth, MSC Director. Photo credit: NASA

  19. Comparison of microdosimetry-based absorbed doses to control tumours and clinically obtained tumour absorbed doses in treatments with 223Ra.

    PubMed

    Minguez Gabina, Pablo; Roeske, John C; Mínguez, Ricardo; Gomez de Iturriaga, Alfonso; Rodeño, Emilia

    2018-06-20

    We performed Monte Carlo simulations in order to determine by means of microdosimetry calculations the average number of hits to the cell nucleus required to reach a tumour control probability (TCP) of 0.9, 〈n<sub>0.9</sub> 〉, for the source geometry of a nucleus embedded in a homogeneous distribution of <sup>223</sup>Ra atoms. From the results obtained and following the MIRD methodology, we determined the values of lesion absorbed doses needed to reach a TCP of 0.9, D<sub>0.9</sub>, for different values of mass density, cell radiosensitivity, nucleus radius and lesion volume. The greatest variation of those absorbed doses occurred with cell radiosensitivity and no dependence was found on mass density. The source geometry used was chosen because we aimed to compare the values of D<sub>0.9</sub> with the lesion absorbed doses obtained from image-based macrodosimetry in treatments of metastatic castration-resistant prostate cancer with <sup>223</sup>Ra which were obtained assuming a homogeneous distribution of <sup>223</sup>Ra atoms within the lesion. In a comparison with a study including 29 lesions, results showed that even for the case of the most radiosensitive cells simulated, 45% of the lesions treated following a schedule of two cycles of 110 kBq/kg body mass would receive absorbed doses below the values of D<sub>0.9</sub> determined in this study. © 2018 Institute of Physics and Engineering in Medicine.

  20. Gamow-Teller transitions between proton h11/2 and neutron h9/2 partner orbitals in 140I

    NASA Astrophysics Data System (ADS)

    Moon, B.; Moon, C.-B.; Odahara, A.; Lozeva, R.; Söderström, P.-A.; Nishimura, S.; Yuan, C.; Hong, B.; for theNP1112-RIBF87 Collaboration

    2018-04-01

    The excited states of the neutron-rich nucleus 140I were, for the first time, investigated by a β-delayed γ-ray spectroscopy. The parent nuclide 140Te was produced through the in-flight fission of the 238U beam at 345 MeV per nucleon on a 9Be target at the Radioactive Isotope Beam Factory (RIBF), RIKEN in Japan. The half-life of 140Te was measured to be 350(5) ms and the spin-parity of ground state of 140I was found to be 2-. The spin-parities of three levels at 926, 1188, and 1787 keV were assigned as 1+ based on log f t values. These allowed Gamow-Teller (G-T) transition-states could be interpreted as the transformation of a neutron in the h9/2 orbital into a proton in the h11/2 orbital. Systematic features of level structures and G-T transitions are discussed in the frameworks of the large-scale shell model and deformed shell model.

  1. Human-Centered Design of Human-Computer-Human Dialogs in Aerospace Systems

    NASA Technical Reports Server (NTRS)

    Mitchell, Christine M.

    1998-01-01

    A series of ongoing research programs at Georgia Tech established a need for a simulation support tool for aircraft computer-based aids. This led to the design and development of the Georgia Tech Electronic Flight Instrument Research Tool (GT-EFIRT). GT-EFIRT is a part-task flight simulator specifically designed to study aircraft display design and single pilot interaction. ne simulator, using commercially available graphics and Unix workstations, replicates to a high level of fidelity the Electronic Flight Instrument Systems (EFIS), Flight Management Computer (FMC) and Auto Flight Director System (AFDS) of the Boeing 757/767 aircraft. The simulator can be configured to present information using conventional looking B757n67 displays or next generation Primary Flight Displays (PFD) such as found on the Beech Starship and MD-11.

  2. Localization of aPKC lambda/iota and its interacting protein, Lgl2, is significantly associated with lung adenocarcinoma progression.

    PubMed

    Imamura, Naoko; Horikoshi, Yosuke; Matsuzaki, Tomohiko; Toriumi, Kentaro; Kitatani, Kanae; Ogura, Go; Masuda, Ryota; Nakamura, Naoya; Takekoshi, Susumu; Iwazaki, Masayuki

    2013-12-20

    Atypical protein kinase C lambda/iota (aPKC λ/ι) is expressed in several human cancers; however, the correlation between aPKC λ/ι localization and cancer progression in human lung adenocarcinoma (LAC) remains to be clarified. We found that patients with a high level of aPKC λ/ι expression in LAC had significantly shorter overall survival than those with a low level of aPKC λ/ι expression. In addition, localization of aPKC λ/ι in the apical membrane or at the cell-cell contact was associated with both lymphatic invasion and metastasis. The intercellular adhesion molecule, E-cadherin, was decreased in LACs with highly expressed aPKC λ/ι at the invasion site of tumor cells. This result suggested that the expression levels of aPKC λ/ι and E-cadherin reflect the progression of LAC. On double-immunohistochemical analysis, aPKC λ/ι and Lgl2, a protein that interacts with aPKC λ/ι, were co-localized within LACs. Furthermore, we found that Lgl2 bound the aPKC λ/ι-Par6 complex in tumor tissue by immune-cosedimentation analysis. Apical membrane localization of Lgl2 was correlated with lymphatic invasion and lymph node metastasis. These results thus indicate that aPKC λ/ι expression is altered upon the progression of LAC. This is also the first evidence to show aPKC λ/ι overexpression in LAC and demonstrates that aPKC λ/ι localization at the apical membrane or cell-cell contact is associated with lymphatic invasion and metastasis of the tumor.

  3. The effect of green tea and olive oil on the mutagenic activity of heterocyclic amines extracted from common food consumed in Saudi Arabia.

    PubMed

    Awney, Hala

    2011-05-01

    The effect of green tea (GT) and green tea with olive oil (GT+OL) as antioxidants on the formation and mutagenic activity of heterocyclic aromatic amines (HCAs) extracted from beef shawerma, grilled chicken and fried beef liver was examined. HCAs were extracted by blue rayon, analyzed as spiked and unspiked samples with high-performance liquid chromatography and its mutagenic response was assessed by Sallmonela typhimurium 100 in the Ames test. Surprisingly, GT and GT+OL augmented HCAs measured in beef shawerma and grilled chicken but total HCAs measured in GT+OL were less than GT treatment. Both treatments altered the HCA profile as imidazoquinoline type became the most abundant. In control and GT+OL fried beef liver no HCAs were detected, but Trp-P1 was detected in GT treatment. Generally, the mutagenic response of HCAs measured in GT+OL was less than GT in beef shawerma and grilled chicken. However, the mutagenic response of control and 2% GT+OL fried liver was negative. These data suggest that GT concentrations used in this study may induce free radical formation during the Millared reaction due to its pro-oxidative effect, which augmented the HCAs formed and its mutagenic response. In order to optimize both safety and quality of our diets, more need to be done to fully understand the risk of HCAs in food.

  4. Rhombohedral R3c to orthorhombic Pnma phase transition induced by Y-doping in BiFeO3.

    PubMed

    Graf, Monica Elisabet; Di Napoli, Solange; Barral, Maria Andrea Andrea; Saleh Medina, Leila; Negri, R Martín; Sepliarsky, Marcelo; Llois, Ana María

    2018-05-23

    In this work we study, by means of <i>ab initio</i> calculations, the structural, electronic and magnetic properties of Y-doped BiFeO<sub>3</sub> compounds. We determine that there is a morphotropic phase boundary at an yttrium concentration of (18 ± 2)%, where the structure changes from <i>R3c</i> to <i>Pnma</i>. This structural transition is driven by the chemical pressure induced by the dopant. By analyzing the evolution of the oxygen octahedral tilts we find an enhanced antiferrodistortive distortion when increasing the Y-doping, together with a reduction of the ferroelectric distorsion, that gives rise to a smaller value of the electric polarization. These cooperative effects should lead to a larger canting of the Fe magnetic moments and to a larger ferromagnetic response in the <i>R3c</i> phase, as it is observed in the experiments. . © 2018 IOP Publishing Ltd.

  5. Galaxy formation in Lambda greater than 0 Friedmann models: Consequences for the number counts versus redshift test

    NASA Technical Reports Server (NTRS)

    Martel, Hugo

    1994-01-01

    We study the effect of the cosmological constant Lambda on galaxy formation using a simple spherical top-hat overdensity model. We consider models with Omega(sub 0) = 0.2, lambda(sub 0) = 0, and Omega(sub 0) = 0.2, lambda(sub 0) = 0.8 (where Omega(sub 0) is the density parameter, and lambda(sub 0) identically equal Lambda/3 H(sub 0 exp 2) where H(sub 0) is the Hubble constant). We adjust the initial power spectrum amplitude so that both models reproduce the same large-scale structures. The galaxy formation era in the lambda(sub 0) = 0 model occurs early (z approximately 6) and is very short, whereas in the lambda(sub 0) = 0.8 model the galaxy formation era starts later (z approximately 4), and last much longer, possibly all the way to the present. Consequently, galaxies at low redshift (z less than 1) are significantly more evolved in the lambda(sub 0) = 0 model than in the lambda(sub 0) = 0.8 model. This result implies that previous attempts to determine Lambda using the number counts versus redshift test are probably unreliable.

  6. Study on the Correlation between Gene Expression and Enzyme Activity of Seven Key Enzymes and Ginsenoside Content in Ginseng in Over Time in Ji'an, China.

    PubMed

    Yin, Juxin; Zhang, Daihui; Zhuang, Jianjian; Huang, Yi; Mu, Ying; Lv, Shaowu

    2017-12-11

    Panax ginseng is a traditional medicine. Fresh ginseng is one of the most important industries related to ginseng development, and fresh ginseng of varying ages has different medicinal properties. Previous research has not systematically reported the correlation between changes in key enzyme activity with changes in ginsenoside content in fresh ginseng over time. In this study, for the first time, we use ginseng samples of varying ages in Ji'an and systematically reported the changes in the activity of seven key enzymes (HMGR, FPS, SS, SE, DS, CYP450, and GT). We investigated the content of ginsenoside and gene expression of these key enzymes. Ginsenoside content was measured using HPLC. HPLC, GC-MS, and LC-MS were combined to measure the enzyme activity of the key enzymes. Quantitative PCR was used in the investigation of gene expression. By analyzing the correlation between the enzyme activity and the transcription level of the key enzymes with ginsenoside content, we found that DS and GT enzyme activities are significantly correlated with the ginsenoside content in different ages of ginseng. Our findings might provide a new strategy to discriminate between ginseng of different years. Meanwhile, this research provides important information for the in-depth study of ginsenoside biosynthesis.

  7. Isolation and Characterization of Brewer's Yeast Variants with Improved Fermentation Performance under High-Gravity Conditions▿

    PubMed Central

    Blieck, Lies; Toye, Geert; Dumortier, Françoise; Verstrepen, Kevin J.; Delvaux, Freddy R.; Thevelein, Johan M.; Van Dijck, Patrick

    2007-01-01

    To save energy, space, and time, today's breweries make use of high-gravity brewing in which concentrated medium (wort) is fermented, resulting in a product with higher ethanol content. After fermentation, the product is diluted to obtain beer with the desired alcohol content. While economically desirable, the use of wort with an even higher sugar concentration is limited by the inability of brewer's yeast (Saccharomyces pastorianus) to efficiently ferment such concentrated medium. Here, we describe a successful strategy to obtain yeast variants with significantly improved fermentation capacity under high-gravity conditions. We isolated better-performing variants of the industrial lager strain CMBS33 by subjecting a pool of UV-induced variants to consecutive rounds of fermentation in very-high-gravity wort (>22° Plato). Two variants (GT336 and GT344) showing faster fermentation rates and/or more-complete attenuation as well as improved viability under high ethanol conditions were identified. The variants displayed the same advantages in a pilot-scale stirred fermenter under high-gravity conditions at 11°C. Microarray analysis identified several genes whose altered expression may be responsible for the superior performance of the variants. The role of some of these candidate genes was confirmed by genetic transformation. Our study shows that proper selection conditions allow the isolation of variants of commercial brewer's yeast with superior fermentation characteristics. Moreover, it is the first study to identify genes that affect fermentation performance under high-gravity conditions. The results are of interest to the beer and bioethanol industries, where the use of more-concentrated medium is economically advantageous. PMID:17158628

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

    Albrecht, Simon; Winn, Joshua N.; Marcy, Geoffrey W.

    We measure the sky-projected stellar obliquities ({lambda}) in the multiple-transiting planetary systems KOI-94 and Kepler-25, using the Rossiter-McLaughlin effect. In both cases, the host stars are well aligned with the orbital planes of the planets. For KOI-94 we find {lambda} = -11 Degree-Sign {+-} 11 Degree-Sign , confirming a recent result by Hirano and coworkers. Kepler-25 was a more challenging case, because the transit depth is unusually small (0.13%). To obtain the obliquity, it was necessary to use prior knowledge of the star's projected rotation rate and apply two different analysis methods to independent wavelength regions of the spectra. Themore » two methods gave consistent results, {lambda} = 7 Degree-Sign {+-} 8 Degree-Sign and -0. Degree-Sign 5 {+-} 5. Degree-Sign 7. There are now a total of five obliquity measurements for host stars of systems of multiple-transiting planets, all of which are consistent with spin-orbit alignment. This alignment is unlikely to be the result of tidal interactions because of the relatively large orbital distances and low planetary masses in the systems. In this respect, the multiplanet host stars differ from hot-Jupiter host stars, which commonly have large spin-orbit misalignments whenever tidal interactions are weak. In particular, the weak-tide subset of hot-Jupiter hosts has obliquities consistent with an isotropic distribution (p = 0.6), but the multiplanet hosts are incompatible with such a distribution (p {approx} 10{sup -6}). This suggests that high obliquities are confined to hot-Jupiter systems, and provides further evidence that hot-Jupiter formation involves processes that tilt the planetary orbit.« less

  9. Distributional patterns of Mawsoniidae (Sarcopterygii: Actinistia).

    PubMed

    Miguel, Raphael; Gallo, Valéria; Morrone, Juan J

    2014-03-01

    Mawsoniidae are a fossil family of actinistian fish popularly known as coelacanths, which are found in continental and marine paleoenvironments. The taxon is considered monophyletic, including five valid genera (Axelrodichthys, Chinlea, Diplurus, Mawsonia and Parnaibaia) and 11 genera with some taxonomical controversy (Alcoveria, Changxingia, Garnbergia, Heptanema, Indocoelacanthus, Libys, Lualabaea, Megalocoelacanthus, Moenkopia, Rhipis and Trachymetopon). The genera restricted to the Northern Hemisphere (Diplurus and Chinlea) possess the oldest records (Late Triassic), whereas those found in the Southern Hemisphere (Mawsonia, Axelrodichthys, and Parnaibaia) extend from Late Jurassic to Late Cretaceous, especially in Brazil and Africa. We identified distributional patterns of Mawsoniidae, applying the panbiogeographical method of track analysis, and obtained three generalized tracks (GTs): GT1 (Northeastern Newark) in strata of the Newark Group (Upper Triassic); GT2 (Midwestern Gondwana) in the Lualaba Formation (Upper Jurassic); and GT3 (Itapecuru-Alcântara-Santana) in the Itapecuru-Alcântara-Santana formations (Lower Cretaceous). The origin of Mawsoniidae can be dated to at least Late Triassic of Pangaea. The tectonic events related to the breakup of Pangaea and Gondwana and the evolution of the oceans are suggested as the vicariant events modeling the distribution of this taxon throughout the Mesozoic.

  10. Mass budget of the glaciers and ice caps of the Queen Elizabeth Islands, Canada, from 1991 to 2015

    NASA Astrophysics Data System (ADS)

    Millan, Romain; Mouginot, Jeremie; Rignot, Eric

    2017-02-01

    Recent studies indicate that the glaciers and ice caps in Queen Elizabeth Islands (QEI), Canada have experienced an increase in ice mass loss during the last two decades, but the contribution of ice dynamics to this loss is not well known. We present a comprehensive mapping of ice velocity using a suite of satellite data from year 1991 to 2015, combined with ice thickness data from NASA Operation IceBridge, to calculate ice discharge. We find that ice discharge increased significantly after 2011 in Prince of Wales Icefield, maintained or decreased in other sectors, whereas glacier surges have little impact on long-term trends in ice discharge. During 1991-2005, the QEI mass loss averaged 6.3 ± 1.1 Gt yr-1, 52% from ice discharge and the rest from surface mass balance (SMB). During 2005-2014, the mass loss from ice discharge averaged 3.5 ± 0.2 Gt yr-1 (10%) versus 29.6 ± 3.0 Gt yr-1 (90%) from SMB. SMB processes therefore dominate the QEI mass balance, with ice dynamics playing a significant role only in a few basins.

  11. Numeric Design and Performance Analysis of Solid Oxide Fuel Cell -- Gas Turbine Hybrids on Aircraft

    NASA Astrophysics Data System (ADS)

    Hovakimyan, Gevorg

    The aircraft industry benefits greatly from small improvements in aircraft component design. One possible area of improvement is in the Auxiliary Power Unit (APU). Modern aircraft APUs are gas turbines located in the tail section of the aircraft that generate additional power when needed. Unfortunately the efficiency of modern aircraft APUs is low. Solid Oxide Fuel Cell/Gas Turbine (SOFC/GT) hybrids are one possible alternative for replacing modern gas turbine APUs. This thesis investigates the feasibility of replacing conventional gas turbine APUs with SOFC/GT APUs on aircraft. An SOFC/GT design algorithm was created in order to determine the specifications of an SOFC/GT APU. The design algorithm is comprised of several integrated modules which together model the characteristics of each component of the SOFC/GT system. Given certain overall inputs, through numerical analysis, the algorithm produces an SOFC/GT APU, optimized for specific power and efficiency, capable of performing to the required specifications. The SOFC/GT design is then input into a previously developed quasi-dynamic SOFC/GT model to determine its load following capabilities over an aircraft flight cycle. Finally an aircraft range study is conducted to determine the feasibility of the SOFC/GT APU as a replacement for the conventional gas turbine APU. The design results show that SOFC/GT APUs have lower specific power than GT systems, but have much higher efficiencies. Moreover, the dynamic simulation results show that SOFC/GT APUs are capable of following modern flight loads. Finally, the range study determined that SOFC/GT APUs are more attractive over conventional APUs for longer range aircraft.

  12. Temporal changes in HCV genotype distribution in three different high risk populations in San Francisco, California

    PubMed Central

    2011-01-01

    Background Hepatitis C virus (HCV) genotype (GT) has become an important measure in the diagnosis and monitoring of HCV infection treatment. In the United States (U.S.) HCV GT 1 is reported as the most common infecting GT among chronically infected patients. In Europe, however, recent studies have suggested that the epidemiology of HCV GTs is changing. Methods We assessed HCV GT distribution in 460 patients from three HCV-infected high risk populations in San Francisco, and examined patterns by birth cohort to assess temporal trends. Multiple logistic regression was used to assess factors independently associated with GT 1 infection compared to other GTs (2, 3, and 4). Results Overall, GT 1 was predominant (72.4%), however younger injection drug users (IDU) had a lower proportion of GT 1 infections (54.7%) compared to older IDU and HIV-infected patients (80.5% and 76.6%, respectively). Analysis by birth cohort showed increasing proportions of non-GT 1 infections associated with year of birth: birth before 1970 was independently associated with higher adjusted odds of GT 1: AOR 2.03 (95% CI: 1.23, 3.34). African-Americans as compared to whites also had higher adjusted odds of GT 1 infection (AOR: 3.37; 95% CI: 1.89, 5.99). Conclusions Although, HCV GT 1 remains the most prevalent GT, especially among older groups, changes in GT distribution could have significant implications for how HCV might be controlled on a population level and treated on an individual level. PMID:21810243

  13. Thermoresistant revertants of an Escherichia coli strain carrying tif-1 and ruv mutations: non-suppressibility of ruv by sfi.

    PubMed Central

    Otsuji, N; Iyehara-Ogawa, H

    1979-01-01

    Spontaneous thermoresistant revertants were isolated from Tif1 Ruv- and Tif1 Ruv+ strains of Escherichia coli K-12. They were divided into five groups; backmutants to tif+ and recA structural gene mutants accounted for at least two of these groups. Mutations with an unconditional RecA- phenyotype were detected at a higher frequency in the Tif1 Ruv- strains (65%) than in the Tif1 Ruv+ strains (25%). A third group consisted of revertants exhibiting a RecA- phenotype at low temperature. Revertants with normal recombination ability and UV resistance, but with a thermosensitive defect in propagating lambda bio11 phage, were also isolated (group 4). The alleles responsible for this property were cotransducible with the srl gene, suggesting that they are located at the recA locus. Other revertants, which might carry lex, LEXB, or zab mutations, were UV sensitive and were able to propagate lambda bio11 phage (group 5). The sfi mutation, which suppresses filamentation in the Tif1 and UV-sensitive Lon- strains, does not restore UV resistance of the Ruv- mutant. PMID:374356

  14. Identification of promoter motifs regulating ZmeIF4E expression level involved in maize rough dwarf disease resistance in maize (Zea Mays L.).

    PubMed

    Shi, Liyu; Weng, Jianfeng; Liu, Changlin; Song, Xinyuan; Miao, Hongqin; Hao, Zhuanfang; Xie, Chuanxiao; Li, Mingshun; Zhang, Degui; Bai, Li; Pan, Guangtang; Li, Xinhai; Zhang, Shihuang

    2013-04-01

    Maize rough dwarf disease (MRDD, a viral disease) results in significant grain yield losses, while genetic basis of which is largely unknown. Based on comparative genomics, eukaryotic translation initiation factor 4E (eIF4E) was considered as a candidate gene for MRDD resistance, validation of which will help to understand the possible genetic mechanism of this disease. ZmeIF4E (orthologs of eIF4E gene in maize) encodes a protein of 218 amino acids, harboring five exons and no variation in the cDNA sequence is identified between the resistant inbred line, X178 and susceptible one, Ye478. ZmeIF4E expression was different in the two lines plants treated with three plant hormones, ethylene, salicylic acid, and jasmonates at V3 developmental stage, suggesting that ZmeIF4E is more likely to be involved in the regulation of defense gene expression and induction of local and systemic resistance. Moreover, four cis-acting elements related to plant defense responses, including DOFCOREZM, EECCRCAH1, GT1GAMSCAM4, and GT1CONSENSUS were detected in ZmeIF4E promoter for harboring sequence variation in the two lines. Association analysis with 163 inbred lines revealed that one SNP in EECCRCAH1 is significantly associated with CSI of MRDD in two environments, which explained 3.33 and 9.04 % of phenotypic variation, respectively. Meanwhile, one SNP in GT-1 motif was found to affect MRDD resistance only in one of the two environments, which explained 5.17 % of phenotypic variation. Collectively, regulatory motifs respectively harboring the two significant SNPs in ZmeIF4E promoter could be involved in the defense process of maize after viral infection. These results contribute to understand maize defense mechanisms against maize rough dwarf virus.

  15. Estimating Energy Expenditure with ActiGraph GT9X Inertial Measurement Unit.

    PubMed

    Hibbing, Paul R; Lamunion, Samuel R; Kaplan, Andrew S; Crouter, Scott E

    2018-05-01

    The purpose of this study was to explore whether gyroscope and magnetometer data from the ActiGraph GT9X improved accelerometer-based predictions of energy expenditure (EE). Thirty participants (mean ± SD: age, 23.0 ± 2.3 yr; body mass index, 25.2 ± 3.9 kg·m) volunteered to complete the study. Participants wore five GT9X monitors (right hip, both wrists, and both ankles) while performing 10 activities ranging from rest to running. A Cosmed K4b was worn during the trial, as a criterion measure of EE (30-s averages) expressed in METs. Triaxial accelerometer data (80 Hz) were converted to milli-G using Euclidean norm minus one (ENMO; 1-s epochs). Gyroscope data (100 Hz) were expressed as a vector magnitude (GVM) in degrees per second (1-s epochs) and magnetometer data (100 Hz) were expressed as direction changes per 5 s. Minutes 4-6 of each activity were used for analysis. Three two-regression algorithms were developed for each wear location: 1) ENMO, 2) ENMO and GVM, and 3) ENMO, GVM, and direction changes. Leave-one-participant-out cross-validation was used to evaluate the root mean square error (RMSE) and mean absolute percent error (MAPE) of each algorithm. Adding gyroscope to accelerometer-only algorithms resulted in RMSE reductions between 0.0 METs (right wrist) and 0.17 METs (right ankle), and MAPE reductions between 0.1% (right wrist) and 6.0% (hip). When direction changes were added, RMSE changed by ≤0.03 METs and MAPE by ≤0.21%. The combined use of gyroscope and accelerometer at the hip and ankles improved individual-level prediction of EE compared with accelerometer only. For the wrists, adding gyroscope produced negligible changes. The magnetometer did not meaningfully improve estimates for any algorithms.

  16. Development of in-vitro models to elucidate mechanisms of intrinsic cellular and tissue fluorescence

    NASA Astrophysics Data System (ADS)

    Savage, Howard E.; Kolli, Venkateswara; Saha, Sanjoy; Zhang, Jian C.; Glasgold, Mark; Sacks, Peter G.; Alfano, Robert R.; Schantz, Stimson P.

    1995-04-01

    In vitro cell model systems have been used to study the mechanisms of intrinsic cellular and tissue fluorescence as a potential biomarker for cancer. Phenotypic characteristics of cancer that are different from normal tissue include changes in histoarchitecture, proliferation rates and differentiation. a nitrosmethlybenzylamine (NMBA)/rat esophageal carcinogenesis model (NMBA), a transforming growth factor beta (TGF- (beta) )/normal epithelial cell model, and a retinoic acid (RA)/multicellular tumor spheroid model (RAMTS) were used to assess fluorescence changes associated respectively with changes in histoarchitecture, proliferation rates and differentiation. A xenon based fluorescence spectrophotometer (Mediscience Corp.) was used to collect excitation and emission spectra. Two excitation scans ((lambda) Ex 200-360 nm, (lambda) Em 380 nm; (lambda) Ex 240-430 nm, (lambda) Em 450 nm) and two emission scans ((lambda) Ex 300 nm, (lambda) Em 320-580 nm; (lambda) Ex 340 nm, (lambda) Em 360-660 nm) were used to analyze the three model systems. Using the NMBA model. Differences were seen in the excitation scan ((lambda) Ex 200-360 nm, (lambda) Em 380 nm) and the emission scan ((lambda) Ex 340 nm, (lambda) Em 360-660 nm) when normal rat esophageal tissue was compared to hyperplastic and tumor tissue. In the (TGF-(beta) ) model, differences were seen in the excitation scan ((lambda) Ex 240-430 nm, (lambda) Em 450 nm) when comparing proliferation slowed (TGF-(beta) treated) epithelial cells to their untreated controls. In the RAMTS model, differences were seen with all four scans when RA treated multicellular tumor spheroids (nondifferentiating) were compared to untreated control cells (differentiating). The data indicate that fluorescence changes seen in these model systems may relate to changes in histoarchitecture, proliferation rates and differentiation. Their relationship to in vivo fluorescence changes seen in cancer patients remains to be elucidated.

  17. Preclinical and Clinical Resistance Profile of EDP-239, a Novel Hepatitis C Virus NS5A Inhibitor.

    PubMed

    Owens, Christopher M; Brasher, Bradley B; Polemeropoulos, Alex; Rhodin, Michael H J; McAllister, Nicole; Wong, Kelly A; Jones, Christopher T; Jiang, Lijuan; Lin, Kai; Or, Yat Sun

    2016-10-01

    EDP-239, a potent and selective hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor developed for the treatment of HCV infection, has been investigated in vitro and in vivo This study sought to characterize genotypic changes in the HCV NS5A sequence of genotype 1 (GT1) replicons and to compare those changes to GT1 viral RNA mutations isolated from clinical trial patients. Resistance selection experiments in vitro using a subgenomic replicon identified resistance-associated mutations (RAMs) at GT1a NS5A amino acid positions 24, 28, 30, 31, and 93 that confer various degrees of resistance to EDP-239. Key RAMs were similarly identified in GT1b NS5A at amino acid positions 31 and 93. Mutations F36L in GT1a and A92V in GT1b do not confer resistance to EDP-239 individually but were found to enhance the resistance of GT1a K24R and GT1b Y93H. RAMs were identified in GT1 patients at baseline or after dosing with EDP-239 that were similar to those detected in vitro Baseline RAMs identified at NS5A position 93 in GT1, or positions 28 or 30 in GT1a only, correlated with a reduced treatment response. RAMs at additional positions were also detected and may have contributed to reduced EDP-239 efficacy. The most common GT1a and GT1b RAMs found to persist up to weeks 12, 24, or 48 were those at NS5A positions 28, 30, 31, 58 (GT1a only), and 93. Those RAMs persisting at the highest frequencies up to weeks 24 or 48 were L31M and Q30H/R for GT1a and L31M and Y93H for GT1b. (This study has been registered at ClinicalTrials.gov under identifier NCT01856426.). Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  18. First measurement of the ratio of branching fractions B({lambda}{sub b}{sup 0}{yields}{lambda}{sub c}{sup +}{mu}{sup -}{nu}{sub {mu}})/B({lambda}{sub b}{sup 0}{yields}{lambda}{sub c}{sup +}{pi}{sup -})

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

    Aaltonen, T.; Maki, T.; Mehtala, P.

    2009-02-01

    This article presents the first measurement of the ratio of branching fractions B({lambda}{sub b}{sup 0}{yields}{lambda}{sub c}{sup +}{mu}{sup -}{nu}{sub {mu}})/B({lambda}{sub b}{sup 0}{yields}{lambda}{sub c}{sup +}{pi}{sup -}). Measurements in two control samples using the same technique B(B{sup 0}{yields}D{sup +}{mu}{sup -}{nu}{sub {mu}})/B(B{sup 0}{yields}D{sup +}{pi}{sup -}) and B(B{sup 0}{yields}D*(2010){sup +}{mu}{sup -}{nu}{sub {mu}})/B(B{sup 0}{yields}D*(2010){sup +}{pi}{sup -}) are also reported. The analysis uses data from an integrated luminosity of approximately 172 pb{sup -1} of pp collisions at {radical}(s)=1.96 TeV, collected with the CDF II detector at the Fermilab Tevatron. The relative branching fractions are measured to be (B({lambda}{sub b}{sup 0}{yields}{lambda}{sub c}{sup +}{mu}{sup -}{nu}{sub {mu}})/B({lambda}{sub b}{sup 0}{yields}{lambda}{sub c}{supmore » +}{pi}{sup -}))=16.6{+-}3.0(stat){+-}1.0(syst)(+2.6/-3.4)(PDG){+-}0.3 (EBR), (B(B{sup 0}{yields}D{sup +}{mu}{sup -}{nu}{sub {mu}})/B(B{sup 0}{yields}D{sup +}{pi}{sup -}))9.9{+-}1.0(stat){+-}0.6(syst){+-}0.4(PDG){+-}0.5(EBR), and (B(B{sup 0}{yields}D*(2010){sup +}{mu}{sup -}{nu}{sub {mu}})/B(B{sup 0}{yields}D*(2010){sup +}{pi}{sup -}))=16.5{+-}2.3(stat){+-} 0.6(syst){+-}0.5(PDG){+-}0.8(EBR). The uncertainties are from statistics (stat), internal systematics (syst), world averages of measurements published by the Particle Data Group or subsidiary measurements in this analysis (PDG), and unmeasured branching fractions estimated from theory (EBR), respectively. This article also presents measurements of the branching fractions of four new {lambda}{sub b}{sup 0} semileptonic decays: {lambda}{sub b}{sup 0}{yields}{lambda}{sub c}(2595){sup +}{mu}{sup -}{nu}{sub {mu}}, {lambda}{sub b}{sup 0}{yields}{lambda}{sub c}(2625){sup +}{mu}{sup -}{nu}{sub {mu}}, {lambda}{sub b}{sup 0}{yields}{sigma}{sub c}(2455){sup 0}{pi}{sup +}{mu}{sup -}{nu}{sub {mu}}, and {lambda}{sub b}{sup 0}{yields}{sigma}{sub c}(2455){sup ++}{pi}{sup -}{mu}{sup -}{nu}{sub {mu}}, relative to the branching fraction of the {lambda}{sub b}{sup 0}{yields}{lambda}{sub c}{sup +}{mu}{sup -}{nu}{sub {mu}} decay. Finally, the transverse-momentum distribution of {lambda}{sub b}{sup 0} baryons produced in pp collisions is measured and found to be significantly different from that of B{sup 0} mesons, which results in a modification in the production cross-section ratio {sigma}{sub {lambda}{sub b}{sup 0}}/{sigma}{sub B{sup 0}} with respect to the CDF I measurement.« less

  19. Cloning and Expression of cDNA for Rat Heme Oxygenase

    NASA Astrophysics Data System (ADS)

    Shibahara, Shigeki; Muller, Rita; Taguchi, Hayao; Yoshida, Tadashi

    1985-12-01

    Two cDNA clones for rat heme oxygenase have been isolated from a rat spleen cDNA library in λ gt11 by immunological screening using a specific polyclonal antibody. One of these clones has an insert of 1530 nucleotides that contains the entire protein-coding region. To confirm that the isolated cDNA encodes heme oxygenase, we transfected monkey kidney cells (COS-7) with the cDNA carried in a simian virus 40 vector. The heme oxygenase was highly expressed in endoplasmic reticulum of transfected cells. The nucleotide sequence of the cloned cDNA was determined and the primary structure of heme oxygenase was deduced. Heme oxygenase is composed of 289 amino acids and has one hydrophobic segment at its carboxyl terminus, which is probably important for the insertion of heme oxygenase into endoplasmic reticulum. The cloned cDNA was used to analyze the induction of heme oxygenase in rat liver by treatment with CoCl2 or with hemin. RNA blot analysis showed that both CoCl2 and hemin increased the amount of hybridizable mRNA, suggesting that these substances may act at the transcriptional level to increase the amount of heme oxygenase.

  20. GEMINI-TITAN (GT-11) - EARTH SKY - OUTER SPACE

    NASA Image and Video Library

    1966-09-14

    S66-54677 (14 Sept. 1966) --- India and Ceylon as seen from the orbiting Gemini-11 spacecraft at an altitude of 410 nautical miles during its 26th revolution of Earth. The Indian Ocean is at bottom of picture; at left center is Arabian Sea; and at upper right is Bay of Bengal. The Maldives Islands are near nose of spacecraft. Taken with a modified 70mm Hasselblad camera, using Eastman Kodak, Ektachrome, MS. (S.O. 368) color film. Photo credit: NASA

  1. Militarism and Foreign Conflict Behavior: A Quantitative Study Revisited.

    DTIC Science & Technology

    1982-05-20

    more, or other, indicators could have been dhosen it was felt that than seven were universally aplicable and describe the overall militarized...discussion of each indicator will point out where it varies from the 1972 study, if aplicable . I~f R tmtram an A ~~tg of _ErGtOD& ren for B9alh and...Demonstrations 7 8 Troop Movements 8 5 Severance of Diplomatic Relations 9 9 Military Actions 10 10 Mobilization 11 11 War 12 12 *For a complete description of

  2. Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci.

    PubMed

    Harley, John B; Alarcón-Riquelme, Marta E; Criswell, Lindsey A; Jacob, Chaim O; Kimberly, Robert P; Moser, Kathy L; Tsao, Betty P; Vyse, Timothy J; Langefeld, Carl D; Nath, Swapan K; Guthridge, Joel M; Cobb, Beth L; Mirel, Daniel B; Marion, Miranda C; Williams, Adrienne H; Divers, Jasmin; Wang, Wei; Frank, Summer G; Namjou, Bahram; Gabriel, Stacey B; Lee, Annette T; Gregersen, Peter K; Behrens, Timothy W; Taylor, Kimberly E; Fernando, Michelle; Zidovetzki, Raphael; Gaffney, Patrick M; Edberg, Jeffrey C; Rioux, John D; Ojwang, Joshua O; James, Judith A; Merrill, Joan T; Gilkeson, Gary S; Seldin, Michael F; Yin, Hong; Baechler, Emily C; Li, Quan-Zhen; Wakeland, Edward K; Bruner, Gail R; Kaufman, Kenneth M; Kelly, Jennifer A

    2008-02-01

    Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with complex etiology but strong clustering in families (lambda(S) = approximately 30). We performed a genome-wide association scan using 317,501 SNPs in 720 women of European ancestry with SLE and in 2,337 controls, and we genotyped consistently associated SNPs in two additional independent sample sets totaling 1,846 affected women and 1,825 controls. Aside from the expected strong association between SLE and the HLA region on chromosome 6p21 and the previously confirmed non-HLA locus IRF5 on chromosome 7q32, we found evidence of association with replication (1.1 x 10(-7) < P(overall) < 1.6 x 10(-23); odds ratio = 0.82-1.62) in four regions: 16p11.2 (ITGAM), 11p15.5 (KIAA1542), 3p14.3 (PXK) and 1q25.1 (rs10798269). We also found evidence for association (P < 1 x 10(-5)) at FCGR2A, PTPN22 and STAT4, regions previously associated with SLE and other autoimmune diseases, as well as at > or =9 other loci (P < 2 x 10(-7)). Our results show that numerous genes, some with known immune-related functions, predispose to SLE.

  3. Infrared differential-absorption Mueller matrix spectroscopy and neural network-based data fusion for biological aerosol standoff detection.

    PubMed

    Carrieri, Arthur H; Copper, Jack; Owens, David J; Roese, Erik S; Bottiger, Jerold R; Everly, Robert D; Hung, Kevin C

    2010-01-20

    An active spectrophotopolarimeter sensor and support system were developed for a military/civilian defense feasibility study concerning the identification and standoff detection of biological aerosols. Plumes of warfare agent surrogates gamma-irradiated Bacillus subtilis and chicken egg white albumen (analytes), Arizona road dust (terrestrial interferent), water mist (atmospheric interferent), and talcum powders (experiment controls) were dispersed inside windowless chambers and interrogated by multiple CO(2) laser beams spanning 9.1-12.0 microm wavelengths (lambda). Molecular vibration and vibration-rotation activities by the subject analyte are fundamentally strong within this "fingerprint" middle infrared spectral region. Distinct polarization-modulations of incident irradiance and backscatter radiance of tuned beams generate the Mueller matrix (M) of subject aerosol. Strings of all 15 normalized elements {M(ij)(lambda)/M(11)(lambda)}, which completely describe physical and geometric attributes of the aerosol particles, are input fields for training hybrid Kohonen self-organizing map feed-forward artificial neural networks (ANNs). The properly trained and validated ANN model performs pattern recognition and type-classification tasks via internal mappings. A typical ANN that mathematically clusters analyte, interferent, and control aerosols with nil overlap of species is illustrated, including sensitivity analysis of performance.

  4. [Effects of postnatal lambda-cyhalothrin exposure on synaptic proteins in ICR mouse brain].

    PubMed

    Bao, Xun-Di; Wang, Qu-Nan; Li, Fang-Fang; Chai, Xiao-Yu; Gao, Ye

    2011-04-01

    To evaluate the influence on the synaptic protein expression in different brain regions of ICR mice after lambda-cyhalothrin (LCT) exposure during postnatal period. Two male and 4 female healthy ICR mice were put in one cage. It was set as pregnancy if vaginal plug was founded. Offspring were divided into 5 groups randomly, and exposed to LCT (0.01% DMSO solution) at the doses of 0.1, 1.0 and 10.0 mg/kg by intragastric rout every other day from postnatal days (PND) 5 to PND13, control animals were treated with normal saline or DMSO by the same route. The brains were removed from pups on PND 14, the synaptic protein expression levels in cortex, hippocampus and striatum were measured by western blot. GFAP levels of cortex and hippocampus in the LCT exposure group increased with doses, as compared with control group (P < 0.05), while Tuj protein expression did not change significantly in the various brain regions of ICR mice. GAP-43 protein expression levels in the LCT exposed mouse hippocampus and in female ICR mouse cortex increased with doses, as compared with control group (P < 0.05). Presynaptic protein (Synapsin I) expression levels did not change obviously in various brain regions. However, postsynaptic density protein 95 (PSD95) expression levels of the hippocampus and striatum in male offspring of 10.0 mg/kg LCT group, of cortex of female LCT groups, and of female offspring in all exposure groups, of striatum, in 1.0 or 10.0 mg/kg LCT exposure groups significantly decreased (P < 0.05). Early postnatal exposure to LCT affects synaptic protein expression. These effects may ultimately affect the construction of synaptic connections.

  5. cDNA cloning and analysis of betaine aldehyde dehydrogenase, a salt inducible enzyme in sugar beet

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

    McCue, K.F.; Hanson, A.D.

    1990-05-01

    Betaine accumulates and serves as a compatible osmolyte in some plants subjected to drought or salinity stress. The last enzyme in the betaine biosynthetic pathway is betaine aldehyde dehydrogenase (BADH). The activity of BADH increases in response to increasing salinity levels. This increase in activity corresponds to an increase in protein detectable by immunoblotting, and to an increase in the translatable BADH mRNA. BADH was cloned from a cDNA library constructed in {lambda}gt10 using poly(A){sup +} RNA from sugar beets salinized to 500 mM NaCl. cDNAs were size selected (>1kb) before ligation into the vector, and the library was screenedmore » with a spinach BADH cDNA probe. Three nearly full length clones obtained were confirmed as BADH by their nucleotide and deduced amino acid homology to spinach BADH. Clones averaged 1.8 kb and contained open reading frames of 500 amino acids at 80% identity with spinach BADH. RNA gel blot analysis of poly(A){sup +} RNA indicated that salinization to 500 mM NaCl resulted in a 5-fold increase of BADH mRNA level.« less

  6. Evaluation of Dynamic Changes in Rating of Russian Information Sources of Medical Education Sites.

    PubMed

    Vasilyeva, Irina V; Arseniev, Sergey B

    2016-01-01

    The aim of the present study is to analyze dynamic changes in the rating of information sources of medical literature in the sites of the following electronic libraries (<rsl.ru>, <rssi.ru>, <elibrary.ru>) and the rating of information sources for electronic medical books (<booksmed.com>, <medliter.ru> <medbook.net.ru>). While using the on-line programs Alexa and Cy-pr, we have analyzed their website's rating and identified basic data and time-varying site data obtained for fourteen months. Alexa Rank rating was calculated for each sitemonthly. Our study has shown that the most popular information sources of medical education among the six studied sites for Russian users is <elibrary.ru>; the site <rssi.ru> is at the second place.

  7. A Deep Search for Faint Galaxies Associated with Very Low Redshift C IV Absorbers. III. The Mass- and Environment-dependent Circumgalactic Medium

    NASA Astrophysics Data System (ADS)

    Burchett, Joseph N.; Tripp, Todd M.; Bordoloi, Rongmon; Werk, Jessica K.; Prochaska, J. Xavier; Tumlinson, Jason; Willmer, C. N. A.; O'Meara, John; Katz, Neal

    2016-12-01

    Using Hubble Space Telescope Cosmic Origins Spectrograph observations of 89 QSO sightlines through the Sloan Digital Sky Survey footprint, we study the relationships between C IV absorption systems and the properties of nearby galaxies, as well as the large-scale environment. To maintain sensitivity to very faint galaxies, we restrict our sample to 0.0015\\lt z\\lt 0.015, which defines a complete galaxy survey to L≳ 0.01 L\\ast or stellar mass {M}* ≳ {10}8 {M}⊙ . We report two principal findings. First, for galaxies with impact parameter ρ \\lt 1 {r}{vir}, C IV detection strongly depends on the luminosity/stellar mass of the nearby galaxy. C IV is preferentially associated with galaxies with {M}* \\gt {10}9.5 {M}⊙ ; lower-mass galaxies rarely exhibit significant C IV absorption (covering fraction {f}C={9}-6+12 % for 11 galaxies with {M}* \\lt {10}9.5 {M}⊙ ). Second, C IV detection within the {M}* \\gt {10}9.5 {M}⊙ population depends on environment. Using a fixed-aperture environmental density metric for galaxies with ρ < 160 kpc at z\\lt 0.055, we find that {57}-13+12 % (8/14) of galaxies in low-density regions (regions with fewer than seven L\\gt 0.15 L\\ast galaxies within 1.5 Mpc) have affiliated C IV absorption; however, none (0/7) of the galaxies in denser regions show C IV. Similarly, the C IV detection rate is lower for galaxies residing in groups with dark matter halo masses of {M}{halo}\\gt {10}12.5 {M}⊙ . In contrast to C IV, H I is pervasive in the circumgalactic medium without regard to mass or environment. These results indicate that C IV absorbers with {log} N({{C}} {{IV}})≳ 13.5 {{cm}}-2 trace the halos of {M}* \\gt {10}9.5 {M}⊙ galaxies but also reflect larger-scale environmental conditions.

  8. Physical activity surveillance in the European Union: reliability and validity of the European Health Interview Survey-Physical Activity Questionnaire (EHIS-PAQ).

    PubMed

    Baumeister, Sebastian E; Ricci, Cristian; Kohler, Simone; Fischer, Beate; Töpfer, Christine; Finger, Jonas D; Leitzmann, Michael F

    2016-05-23

    The current study examined the reliability and validity of the European Health Interview Survey-Physical Activity Questionnaire (EHIS-PAQ), a novel questionnaire for the surveillance of physical activity (PA) during work, transportation, leisure time, sports, health-enhancing and muscle-strengthening activities over a typical week. Reliability was assessed by administering the 8-item questionnaire twice to a population-based sample of 123 participants aged 15-79 years at a 30-day interval. Concurrent (inter-method) validity was examined in 140 participants by comparisons with self-report (International Physical Activity Questionnaire-Long Form (IPAQ-LF), 7-day Physical Activity Record (PAR), and objective criterion measures (GT3X+ accelerometer, physical work capacity at 75% (PWC(75%)) from submaximal cycle ergometer test, hand grip strength). The EHIS-PAQ showed acceptable reliability, with a median intraclass correlation coefficient across PA domains of 0.55 (range 0.43-0.73). Compared to the GT3X+ (counts/minutes/day), the EHIS-PAQ underestimated moderate-to-vigorous PA (median difference -11.7, p-value = 0.054). Spearman correlation coefficients (ρ) for validity were moderate-to-strong (ρ's > 0.41) for work-related PA (IPAQ = 0.64, GT3X + =0.43, grip strength = 0.48), transportation-related PA (IPAQ = 0.62, GT3X + =0.43), walking (IPAQ = 0.58), and health-enhancing PA (IPAQ = 0.58, PAR = 0.64, GT3X + =0.44, PWC(75%) = 0.48), and fair-to-poor (ρ's < 0.41) for moderate-to-vigorous aerobic recreational and muscle-strengthening PA. The EHIS-PAQ showed good evidence for reliability and validity for the measurement of PA levels at work, during transportation and health-enhancing PA.

  9. On the nature of the nova-like variable CD-42 deg 14462

    NASA Technical Reports Server (NTRS)

    Guinan, E. F.; Sion, E. M.

    1981-01-01

    Low dispersion long and short wavelength IUE spectra of the nova like system CD-42 deg 14462 were obtained on August 24 U.T. The short wave spectrum exhibits absorption features due to C III (lambda 1175), Lalpha 1216), NV (lambda1240), HeII (lambda 1640), SiIV (lambda1394), NIV (lambda1875) with CIV (lambda1550) as a P Cygni feature with blue shifted absorption suggesting the presence of material leaving the system. Possible interpretations of this object are discussed.

  10. Anti p and anti Lambda production in Si + Au collisions at the AGS

    NASA Technical Reports Server (NTRS)

    Wu, Yue-Dong

    1996-01-01

    (anti (ital p)) and (anti (Lambda)) production in central Si + Au collisions has been measured by E589 at the BNL-AGS. Preliminary (ital m)(sub (perpendicular)) spectra are presented for (anti (ital p))'s and (anti (Lambda))'s. The (ital dn/dy) distribution for (anti (ital p))'s is also presented. Based on the (anti (ital p)) and (anti (Lambda)) measurements, (anti (Lambda))/(anti (ital p)) ratios are calculated in the rapidity range of 1.1-1.5.

  11. ASYMMETRIC ABSORPTION PROFILES OF Ly{alpha} AND Ly{beta} IN DAMPED Ly{alpha} SYSTEMS

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

    Lee, Hee-Won, E-mail: hwlee@sejong.ac.kr

    2013-08-01

    Damped Ly{alpha} systems observed in the quasar spectra are characterized by a high neutral hydrogen column density, N{sub HI} > 2 x 10{sup 20} cm{sup -2}. The absorption wing profiles are often fitted using the Voigt function due to the fact that the scattering cross section near the resonant line center is approximately described by the Lorentzian function. Since a hydrogen atom has infinitely many p states that participate in the electric dipole interaction, the cross section starts to deviate from the Lorentzian in an asymmetric way in the line wing regions. We investigate this asymmetry in the absorption linemore » profiles around Ly{alpha} and Ly{beta} as a function of the neutral hydrogen column density N{sub HI}. In terms of {Delta}{lambda} {identical_to} {lambda} - {lambda}{sub {alpha}}, we expand the Kramers-Heisenberg formula around Ly{alpha} to find {sigma}({lambda}) {approx_equal} (0.5f{sub 12}){sup 2}{sigma}{sub T}({Delta}{lambda}/{lambda}{sub {alpha}}){sup -2}[1 + 3.792({Delta}{lambda}/{lambda}{sub {alpha}})], where f{sub 12} and {sigma}{sub T} are the oscillator strength of Ly{alpha} and the Thomson scattering cross section, respectively. In terms of {Delta}{lambda}{sub 2} {identical_to} {lambda} - {lambda}{sub {beta}} in the vicinity of Ly{beta}, the total scattering cross section, given as the sum of cross sections for Rayleigh and Raman scattering, is shown to be {sigma}({lambda}) {approx_equal} {sigma}{sub T}(0.5f{sub 13}){sup 2}(1 + R{sub 0})({Delta}{lambda}{sub 2}/{lambda}{sub {beta}}){sup -2}[1 - 24.68({Delta}{lambda}{sub 2}/{lambda}{sub {beta}})] with f{sub 13} and the factor R{sub 0} = 0.1342 being the oscillator strength for Ly{beta} and the ratio of the Raman cross section to Rayleigh cross section, respectively. A redward asymmetry develops around Ly{alpha}, whereas a blue asymmetry is obtained for Ly{beta}. The absorption center shifts are found to be almost proportional to the neutral hydrogen column density.« less

  12. Infrared Color Selection of Massive Galaxies at z > 3

    NASA Astrophysics Data System (ADS)

    Wang, T.; Elbaz, D.; Schreiber, C.; Pannella, M.; Shu, X.; Willner, S. P.; Ashby, M. L. N.; Huang, J.-S.; Fontana, A.; Dekel, A.; Daddi, E.; Ferguson, H. C.; Dunlop, J.; Ciesla, L.; Koekemoer, A. M.; Giavalisco, M.; Boutsia, K.; Finkelstein, S.; Juneau, S.; Barro, G.; Koo, D. C.; Michałowski, M. J.; Orellana, G.; Lu, Y.; Castellano, M.; Bourne, N.; Buitrago, F.; Santini, P.; Faber, S. M.; Hathi, N.; Lucas, R. A.; Pérez-González, P. G.

    2016-01-01

    We introduce a new color selection technique to identify high-redshift, massive galaxies that are systematically missed by Lyman-break selection. The new selection is based on the H160 (H) and Infrared Array Camera (IRAC) 4.5 μm bands, specifically H-[4.5]\\gt 2.25 mag. These galaxies, called “HIEROs,” include two major populations that can be separated with an additional J - H color. The populations are massive and dusty star-forming galaxies at z\\gt 3 ({JH}-{blue}) and extremely dusty galaxies at z≲ 3 ({JH}-{red}). The 350 arcmin2 of the GOODS-North and GOODS-South fields with the deepest Hubble Space Telescope (HST)/Wide Field Camera 3 (WFC3) near-infrared and IRAC data contain as many as 285 HIEROs down to [4.5]\\lt 24 mag. Inclusion of the most extreme HIEROs, not even detected in the H band, makes this selection particularly complete for the identification of massive high-redshift galaxies. We focus here primarily on {JH}-{blue} (z\\gt 3) HIEROs, which have a median photometric redshift < z> ˜ 4.4 and stellar mass {M}*˜ {10}10.6 {M}⊙ and are much fainter in the rest-frame UV than similarly massive Lyman-break galaxies (LBGs). Their star formation rates (SFRs), derived from their stacked infrared spectral energy distributions (SEDs), reach ˜240 {M}⊙ yr-1, leading to a specific SFR, {{sSFR}}\\equiv {{SFR}}/{M}*˜ 4.2 Gyr-1, suggesting that the sSFRs for massive galaxies continue to grow at z\\gt 2 but at a lower growth rate than from z = 0 to z = 2. With a median half-light radius of 2 kpc, including ˜ 20% as compact as quiescent (QS) galaxies at similar redshifts, {JH}-{blue} HIEROs represent perfect star-forming progenitors of the most massive ({M}*≳ {10}11.2 {M}⊙ ) compact QS galaxies at z˜ 3 and have the right number density. HIEROs make up ˜ 60% of all galaxies with {M}*\\gt {10}10.5 {M}⊙ identified at z\\gt 3 from their photometric redshifts. This is five times more than LBGs with nearly no overlap between the two populations. While HIEROs make up 15%-25% of the total SFR density at z˜ 4-5, they completely dominate the SFR density taking place in {M}*\\gt {10}10.5 {M}⊙ galaxies, and HIEROs are therefore crucial to understanding the very early phase of massive galaxy formation.

  13. Opaque mineralogy and resource potential of placer gold in the stream sediments between Duba and Al Wajh, Red Sea coast, northwestern Saudi Arabia

    NASA Astrophysics Data System (ADS)

    Moufti, Asaad M. B.

    2014-11-01

    Mineralogical studies revealed that the stream sediments in northwestern Saudi Arabia between Duba and Al Wajh on the Red Sea coast are auriferous and can represent a potential source of easily recoverable placer gold. The detailed ore microscopic study supported by fire assay data of stream sediments at the southern sector of Duba-Al Wajh (Wadi Al Miyah, Wadi Haramil and Wadi Thalbah) in NW Saudi Arabia show economic concentrations of gold in their silt fraction (40-63 μm). However, particles of extremely fine “dusty” gold (⩽40 μm in size) are identified in most stations as independent grains. The maximum gold content in the samples of Wadi Al Miyah is 13.61 wt% which is reported for the light fraction (⩽40 μm). Maximum gold content in the heavy fractions of Wadi Haramil stream sediments amounts 6.90 g/t Au in a relatively coarse fraction (63-125 μm). The size still fulfills the silt fraction, but the coarsening of gold can be correlated with either original size of native gold in the Neoproterozoic mineralized zone or/and distance of transportation. It appears that the most gold-rich fractions of the analyzed samples are those from Wadi Thalbah. They have the highest index figure, which suggests that its placer gold may be economically exploitable. Gold content in the heavy fractions of samples from Wadi Thalbah is high and lies within a wide range (6.27-28.83 g/t), except for a single sample collected at the upstream with 0.77 g/t Au only. Fire assay data of samples from three wadis at the northern sector show that their gold content is clearly lower than in the samples from the southern sector. Only few samples from Wadi South Marwah are promising because they contain reasonable gold content (3.10-3.60 g/t) before heavy liquid separation. The two samples give gold content up to 11.03 g/t in their heavy mineral concentrate. The heavy fractions from both Wadi Al Amud and Wadi Salma are poor in gold where the maximum content of the metal in these concentrates are 1.32 and 1.17 g/t, respectively. Generally, the heavy mineral concentrates of both wadis contain ⩽1 g/t Au which is presently uneconomic. Generally, fire assay data of gold proved that samples from the wadis in the southern sectors are more promising for future gold exploration and exploitation.

  14. Quantitative proteomics reveals the mechanism and consequence of gliotoxin-mediated dysregulation of the methionine cycle in Aspergillus niger.

    PubMed

    Manzanares-Miralles, Lara; Sarikaya-Bayram, Özlem; Smith, Elizabeth B; Dolan, Stephen K; Bayram, Özgür; Jones, Gary W; Doyle, Sean

    2016-01-10

    Gliotoxin (GT) is a redox-active metabolite, produced by Aspergillus fumigatus, which inhibits the growth of other fungi. Here we demonstrate how Aspergillus niger responds to GT exposure. Quantitative proteomics revealed that GT dysregulated the abundance of 378 proteins including those involved in methionine metabolism and induced de novo abundance of two S-adenosylmethionine (SAM)-dependent methyltransferases. Increased abundance of enzymes S-adenosylhomocysteinase (p=0.0018) required for homocysteine generation from S-adenosylhomocysteine (SAH), and spermidine synthase (p=0.0068), involved in the recycling of Met, was observed. Analysis of Met-related metabolites revealed significant increases in the levels of Met and adenosine, in correlation with proteomic data. Methyltransferase MT-II is responsible for bisthiobis(methylthio)gliotoxin (BmGT) formation, deletion of MT-II abolished BmGT formation and led to increased GT sensitivity in A. niger. Proteomic analysis also revealed that GT exposure also significantly (p<0.05) increased hydrolytic enzyme abundance, including glycoside hydrolases (n=22) and peptidases (n=16). We reveal that in an attempt to protect against the detrimental affects of GT, methyltransferase-mediated GT thiomethylation alters cellular pathways involving Met and SAM, with consequential dysregulation of hydrolytic enzyme abundance in A. niger. Thus, it provides new opportunities to exploit the response of GT-naïve fungi to GT. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. The Probiotic Escherichia coli Strain Nissle 1917 Combats Lambdoid Bacteriophages stx and λ.

    PubMed

    Bury, Susanne; Soundararajan, Manonmani; Bharti, Richa; von Bünau, Rudolf; Förstner, Konrad U; Oelschlaeger, Tobias A

    2018-01-01

    Shiga toxin (Stx) producing E. coli (STEC) such as Enterohemorrhagic E. coli (EHEC) are the major cause of foodborne illness in humans. In vitro studies showed the probiotic Escherichia coli strain Nissle 1917 (EcN) to efficiently inhibit the production of Stx. Life threatening EHEC strains as for example the serotype O104:H4, responsible for the great outbreak in 2011 in Germany, evolutionary developed from certain E. coli strains which got infected by stx2 -encoding lambdoid phages turning the E. coli into lysogenic and subsequently Stx producing strains. Since antibiotics induce stx genes and Stx production, EHEC infected persons are not recommended to be treated with antibiotics. Therefore, EcN might be an alternative medication. However, because even commensal E. coli strains might be converted into Stx-producers after becoming host to a stx encoding prophage, we tested EcN for stx -phage genome integration. Our experiments revealed the resistance of EcN toward not only stx -phages but also against lambda-phages. This resistance was not based on the lack of or by mutated phage receptors. Rather it involved the expression of a phage repressor ( pr ) gene of a defective prophage in EcN which was able to partially protect E. coli K-12 strain MG1655 against stx and lambda phage infection. Furthermore, we observed EcN to inactivate phages and thereby to protect E. coli K-12 strains against infection by stx - as well as lambda-phages. Inactivation of lambda-phages was due to binding of lambda-phages to LamB of EcN whereas inactivation of stx -phages was caused by a thermostable protein of EcN. These properties together with its ability to inhibit Stx production make EcN a good candidate for the prevention of illness caused by EHEC and probably for the treatment of already infected people.

  16. The Dependence of Cirrus Gamma Size Distributions Expressed as Volumes in N(sub 0)-Lambda-Mu Phase Space and Bulk Cloud Properties on Environmental Conditions: Results from the Small Ice Particles in Cirrus Experiment (SPARTICUS)

    NASA Technical Reports Server (NTRS)

    Jackson, Robert C.; McFarquhar, Greg M.; Fridlind, Ann M.; Atlas, Rachel

    2015-01-01

    The variability of cirrus ice microphysical properties is investigated using observations obtained during the Small Particles in Cirrus (SPARTICUS) campaign. An existing approach that represents a size distribution (SD) as a single gamma function using an ellipsoid of equally realizable solutions in (N(sub 0), lambda, mu) phase space is modified to automatically identify multiple modes in SDs and characterize each mode by such an ellipsoid. The modified approach is applied to ice crystals with maximum dimension D greater than15 micrometers collected by the 2-D stereo and 2-D precipitation probes on the Stratton Park Engineering Company Learjet. The dependencies of N(sub 0), mu, and lambda from each mode, total number concentration, bulk extinction, ice water content (IWC), and mass median maximum dimension D(sub mm) as a function of temperature T and cirrus type are then analyzed. The changes in the observed codependencies between N(sub 0), mu, and lambda, bulk extinction, IWC, and D(sub mm) with environmental conditions indicate that particles were larger at higher T during SPARTICUS. At most two modes were observed in any SD during SPARTICUS, with the average boundary between them at 115 micrometers, similar to past studies not using probes with shatter mitigating tips and artifact removal algorithms. The bimodality of the SDs increased with T. This and the differences in N(sub 0), mu, and lambda between the modes suggest that particles with smaller D nucleated more recently than particles with larger D, which grew via vapor deposition and aggregation. Because smaller crystals, whose concentrations are uncertain, make marginal contributions to higher order moments, the use of higher moments for evaluating model fields is suggested.

  17. Tidal Amplitude for a Self-gravitating, Compressible Sphere

    NASA Astrophysics Data System (ADS)

    Hurford, T. A.; Greenberg, R.

    2001-11-01

    Most modern evaluations of tidal amplitude derive from the approach presented by Love [1]. Love's analysis for a homogeneous sphere assumed an incompressible material, which required introduction of a non-rigorously justified pressure term. We solve the more general case of arbitrary compressibility, which allows for a more straightforward derivation. We find the h2 love number of a body of radius R, density ρ , and surface gravity g to be h2 = \\Bigg[\\frac{{5}/{2}}{1+\\frac{19 \\mu}{2 \\rho g R}}\\Bigg] \\Bigg\\{ \\frac{2 \\rho g R (35+28\\frac{\\mu}{\\lambda}) + 19 \\mu (35+28\\frac{\\mu}{\\lambda})} {2 \\rho g R (35+31\\frac{\\mu}{\\lambda}) + 19 \\mu (35+{490}/{19}\\frac{\\mu}{\\lambda})}\\Bigg\\} λ the Lamé constant. This h2 is the product of Love's expression for h2 (in square brackets) and a ``compressibility-correction'' factor (in \\{\\} brackets). Unlike Love's expression, this result is valid for any degree of compressibility (i.e. any λ ). For the incompressible case (λ -> ∞ ) the correction factor approaches 1, so that h2 matches the classical form given by Love. In reality, of course, materials are not incompressible and the difference between our solution and Love's is significant. Assuming that the elastic terms dominate over the gravitational contribution (i.e. 19 μ /(2 ρ g R) >> 1), our solution can be ~ 7% percent larger than Love's solution for large μ /λ . If the gravity dominates (i.e. 19 μ /(2 ρ g R) << 1), our solution is ~ 10 % smaller than Love's solution for large μ /λ . For example, a rocky body (μ /λ ~ 1 [2]), Earth-sized (19μ /(2 ρ g R) ~ 1) body, h2 would be reduced by about 1% from the classical formula. Similarly, under some circumstances the l2 Love number for a uniform sphere could be 22% smaller than Love's evaluation. [1] Love, A.E.H., A Treatise on the Mathematical Theory of Elasticity, New York Dover Publications, 1944 [2] Kaula, W.M., An Introduction to Planetary Physics: The Terrestrial Planets, John Wiley & Sons, Inc., 1968

  18. The First Prokaryotic Trehalose Synthase Complex Identified in the Hyperthermophilic Crenarchaeon Thermoproteus tenax

    PubMed Central

    Bräsen, Christopher; Hensel, Reinhard; Lupas, Andrei N.; Brinkmann, Henner; Siebers, Bettina

    2013-01-01

    The role of the disaccharide trehalose, its biosynthesis pathways and their regulation in Archaea are still ambiguous. In Thermoproteus tenax a fused trehalose-6-phosphate synthase/phosphatase (TPSP), consisting of an N-terminal trehalose-6-phosphate synthase (TPS) and a C-terminal trehalose-6-phosphate phosphatase (TPP) domain, was identified. The tpsp gene is organized in an operon with a putative glycosyltransferase (GT) and a putative mechanosensitive channel (MSC). The T. tenax TPSP exhibits high phosphatase activity, but requires activation by the co-expressed GT for bifunctional synthase-phosphatase activity. The GT mediated activation of TPS activity relies on the fusion of both, TPS and TPP domain, in the TPSP enzyme. Activation is mediated by complex-formation in vivo as indicated by yeast two-hybrid and crude extract analysis. In combination with first evidence for MSC activity the results suggest a sophisticated stress response involving TPSP, GT and MSC in T. tenax and probably in other Thermoproteales species. The monophyletic prokaryotic TPSP proteins likely originated via a single fusion event in the Bacteroidetes with subsequent horizontal gene transfers to other Bacteria and Archaea. Furthermore, evidence for the origin of eukaryotic TPSP fusions via HGT from prokaryotes and therefore a monophyletic origin of eukaryotic and prokaryotic fused TPSPs is presented. This is the first report of a prokaryotic, archaeal trehalose synthase complex exhibiting a much more simple composition than the eukaryotic complex described in yeast. Thus, complex formation and a complex-associated regulatory potential might represent a more general feature of trehalose synthesizing proteins. PMID:23626675

  19. FORECAST FOR THE PLANCK PRECISION ON THE TENSOR-TO-SCALAR RATIO AND OTHER COSMOLOGICAL PARAMETERS

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

    Burigana, C.; Gruppuso, A.; Mandolesi, N.

    2010-11-20

    The Planck satellite, successfully launched on 2009 May 14 to measure with unprecedented accuracy the primary cosmic microwave background (CMB) anisotropies, is operating as expected. The Standard Model of the Universe ('concordance' model) provides the current realistic context to analyze the CMB and other cosmological/astrophysical data, inflation in the early universe being part of it. The Planck performance for the crucial primordial parameter r, the tensor-to-scalar ratio related to primordial B-mode polarization, will depend on the quality of data analysis and interpretation. The Ginzburg-Landau (G-L) approach to inflation allows us to take high benefit of the CMB data. The fourth-degreemore » double-well inflaton potential gives an excellent fit to the current CMB+LSS data. We evaluate the Planck precision to the recovery of cosmological parameters, taking into account a reasonable toy model for residuals of systematic effects of instrumental and astrophysical origin based on publicly available information. We use and test two relevant models: the {Lambda}CDMr model, i.e., the standard {Lambda}CDM model augmented by r, and the {Lambda}CDMrT model, where the scalar spectral index, n{sub s} , and r are related through the theoretical 'banana-shaped' curve r = r(n{sub s}) coming from the G-L theory with a double-well inflaton potential. In the latter case, the analytical expressions for n{sub s} and r are imposed as a hard constraint in a Monte Carlo Markov Chain (MCMC) data analysis. We consider two C{sub l}-likelihoods (with and without B modes) and take into account the white noise sensitivity of Planck (LFI and HFI) in the 70, 100, and 143 GHz channels as well as the residuals from systematic errors and foregrounds. We also consider a cumulative channel of the three mentioned. We produce the sky (mock data) for the CMB multipoles C{sup TT}{sub l} , C{sup TE}{sub l} , C{sup EE}{sub l} , and C{sup BB}{sub l} from the {Lambda}CDMr and {Lambda}CDMrT models and obtain the cosmological parameter marginalized likelihood distributions for the two models. Foreground residuals affect only the cosmological parameters sensitive to the B modes. As expected, the likelihood r distribution is more clearly peaked near the fiducial value (r = 0.0427) in the {Lambda}CDMrT model than in the {Lambda}CDMr model. The best value for r in the presence of residuals turns out to be about r {approx_equal} 0.04 for both the {Lambda}CDMr and the {Lambda}CDMrT models. The {Lambda}CDMrT model is very stable; its distributions do not change by including residuals and the B modes. For r we find 0.028 < r < 0.116 at a 95% confidence level (CL) with the best value r = 0.04. We also compute the B mode detection probability by the most sensitive HFI-143 channel. At the level of foreground residual equal to 30% of our toy model, only a 68% CL (1{sigma}) detection is very likely. For a 95% CL detection (2{sigma}), the level of foreground residual should be reduced to 10% or lower of the adopted toy model. The lower bounds (and most probable value) we infer for r support the searching of CMB B-mode polarization in the current data as well as the planned CMB missions oriented toward B polarization.« less

  20. Accelerometer measured daily physical activity and sedentary pursuits--comparison between two models of the Actigraph and the importance of data reduction.

    PubMed

    Tanha, Tina; Tornberg, Åsa; Dencker, Magnus; Wollmer, Per

    2013-10-31

    Very few validation studies have been performed between different generations of the commonly used Actigraph accelerometers. We compared daily physical activity data generated from the old generation Actigraph model 7164 with the new generation Actigraph GT1M accelerometer in 15 young females for eight consecutive days. We also investigated if different wear time thresholds had any impact on the findings. Minutes per day of moderate and vigorous physical activity (MVPA), vigorous physical activity (VPA) and very vigorous physical activity (VVPA) were calculated. Moreover, minutes of sedentary pursuits per day were calculated. There were significant (P < 0.05) differences between the Actigraph 7164 and the GT1M concerning MVPA (61 ± 21vs. 56 ± 23 min/day), VPA (12 ± 8 vs. 9 ± 3 min/day) and VVPA (3.2 ± 3.0 vs. 0.3 ± 1.1 min/day). The different wear time thresholds had little impact on minutes per day in different intensities. Median minutes of sedentary pursuits per day ranged from 159 to 438 minutes depending on which wear time threshold was used (i.e. 10, 30 or 60 minutes), whereas very small differences were observed between the two different models. Data from the old generation Actigraph 7164 and the new generation Actigraph GT1M accelerometers differ, where the Actigraph GT1M generates lower minutes spent in free living physical activity. Median minutes of sedentary pursuits per day are highly dependent on which wear time threshold that is used, and not by accelerometer model.

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