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Sample records for target inactivation analysis

  1. Radiation inactivation analysis of enzymes. Effect of free radical scavengers on apparent target sizes

    International Nuclear Information System (INIS)

    Eichler, D.C.; Solomonson, L.P.; Barber, M.J.; McCreery, M.J.; Ness, G.C.

    1987-01-01

    In most cases the apparent target size obtained by radiation inactivation analysis corresponds to the subunit size or to the size of a multimeric complex. In this report, we examined whether the larger than expected target sizes of some enzymes could be due to secondary effects of free radicals. To test this proposal we carried out radiation inactivation analysis on Escherichia coli DNA polymerase I, Torula yeast glucose-6-phosphate dehydrogenase, Chlorella vulgaris nitrate reductase, and chicken liver sulfite oxidase in the presence and absence of free radical scavengers (benzoic acid and mannitol). In the presence of free radical scavengers, inactivation curves are shifted toward higher radiation doses. Plots of scavenger concentration versus enzyme activity showed that the protective effect of benzoic acid reached a maximum at 25 mM then declined. Mannitol alone had little effect, but appeared to broaden the maximum protective range of benzoic acid relative to concentration. The apparent target size of the polymerase activity of DNA polymerase I in the presence of free radical scavengers was about 40% of that observed in the absence of these agents. This is considerably less than the minimum polypeptide size and may reflect the actual size of the polymerase functional domain. Similar effects, but of lesser magnitude, were observed for glucose-6-phosphate dehydrogenase, nitrate reductase, and sulfite oxidase. These results suggest that secondary damage due to free radicals generated in the local environment as a result of ionizing radiation can influence the apparent target size obtained by this method

  2. Comparison of the calcium release channel of cardiac and skeletal muscle sarcoplasmic reticulum by target inactivation analysis

    International Nuclear Information System (INIS)

    McGrew, S.G.; Inui, Makoto; Chadwick, C.C.; Boucek, R.J. Jr.; Jung, C.Y.; Fleischer, S.

    1989-01-01

    The calcium release channel of sarcoplasmic reticulum which triggers muscle contraction in excitation-contraction coupling has recently been isolated. The channel has been found to be morphologically identical with the feet structures of the junctional face membrane of terminal cisternae and consists of an oligomer of a unique high molecular weight polypeptide. In this study, the authors compare the target size of the calcium release channel from heart and skeletal muscle using target inactivation analysis. The target molecular weights of the calcium release channel estimated by measuring ryanodine binding after irradiation are similar for heart (139,000) and skeletal muscle (143,000) and are smaller than the monomeric unit (estimated to be about 360,000). The target size, estimated by measuring polypeptide remaining after irradiation, was essentially the same for heart and skeletal muscle, 1,061,000 and 1,070,000, respectively, indicating an oligomeric association of protomers. Thus, the calcium release channel of both cardiac and skeletal muscle reacts uniquely with regard to target inactivation analysis in that (1) the size by ryanodine binding is smaller than the monomeric unit and (2) a single hit leads to destruction of more than one polypeptide, by measuring polypeptide remaining. The target inactivation analysis studies indicate that heart and skeletal muscle receptors are structurally very similar

  3. Target size analysis of bioactive substances by radiation inactivation. Comparison with electron beam and. gamma. -ray

    Energy Technology Data Exchange (ETDEWEB)

    Kume, Tamikazu; Watanabe, Yuhei; Ishigaki, Isao; Hirose, Shigehisa

    1988-11-01

    The molecular sizes of various bioactive substances can be measured by the radiation inactivation method. The high energy electron beam (10 MeV) and /sup 60/Co-..gamma.. ray are mainly used for radiation inactivation method. When the practical electron accelerator (/similar to/ 3 MeV) is used for the method, the problems such as penetration and increase of temperature will arise. In this paper the radiation inactivation using 3MeV electron beam is investigated by comparison with ..gamma..-ray. When the plate type glass ampules (glass thickness 1 +- 0.1 mm) were used as the irradiation vessels, relatively uniform dose distribution was obtained. The temperature increased only from 21 degC to 35 degC by irradiation (0.77 mA, 100 passes, 100 kGy). Under the irradiation condition mentioned above, the molecular size of three enzymes were calculated from D/sub 37/ doses. The molecular sizes obtained by electron beam and ..gamma..-ray were 14,000 and 17,000 respectively for lysozyme, 33,000 for pepsin, and 191,000 and 164,000 for yeast alcohol dehydrogenase. These values agreed closely with the reported molecular weight, suggesting that the 3 MeV electron beam can also be used for the radiation inactivation under limited conditions.

  4. Difunctional bacteriophage conjugated with photosensitizers for Candida albicans-targeting photodynamic inactivation.

    Science.gov (United States)

    Dong, Shuai; Shi, Hongxi; Zhang, Xintong; Chen, Xi; Cao, Donghui; Mao, Chuanbin; Gao, Xiang; Wang, Li

    2018-01-01

    Candida albicans is the most prevalent fungal pathogen of the human microbiota, causing infections ranging from superficial infections of the skin to life-threatening systemic infections. Due to the increasing occurrence of antibiotic-resistant C. albicans strains, new approaches to control this pathogen are needed. Photodynamic inactivation is an emerging alternative to treat infections based on the interactions between visible light and photosensitisers, in which pheophorbide a (PPA) is a chlorophyll-based photosensitizer that could induce cell death after light irradiation. Due to PPA's phototoxicity and low efficiency, the main challenge is to implement photosensitizer cell targeting and attacking. In this study, PPA was conjugated with JM-phage by EDC/NHS crosslinking. UV-Vis spectra was used to determine the optimum conjugation percentages of PPA and JM-phage complex for photodynamic inactivation. After photodynamic inactivation, the efficacy of PPA-JM-phage was assessed by performing in vitro experiments, such as MTS assay, scanning electron microscopy, measurement of dysfunctional mitochondria, ROS accumulation, S cell arrest and apoptotic pathway. A single-chain variable-fragment phage (JM) with high affinity to MP65 was screened from human single-fold single-chain variable-fragment libraries and designed as a binding target for C. albicans cells. Subsequently, PPa was integrated into JM phage to generate a combined nanoscale material, which was called PPA-JM-phage. After photodynamic inactivation, the growth of C. albicans was inhibited by PPA-JM-phage and apoptosis was observed. Scanning electron microscopy analysis revealed shrinking and rupturing of C. albicans . We also found that depolarization of mitochondrial membrane potential was decreased and intracellular reactive oxygen species levels were elevated significantly in C. albicans inhibited by PPA-JM-phage. Additionally, PPA-JM-phage also lead to S-phase arrest, and metacaspase activation

  5. Difunctional bacteriophage conjugated with photosensitizers for Candida albicans-targeting photodynamic inactivation

    Directory of Open Access Journals (Sweden)

    Dong S

    2018-04-01

    Full Text Available Shuai Dong,1,2 Hongxi Shi,1 Xintong Zhang,1,2 Xi Chen,1 Donghui Cao,2 Chuanbin Mao,3,4 Xiang Gao,1 Li Wang1 1Key Laboratory of Molecular Epigenetics of Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, 2First Hospital of Jilin University, Changchun, Jilin, 3School of Materials Science and Engineering, Zhejiang University, Hangzhou, Zhejiang, China; 4Department of Chemistry and Biochemistry, Stephenson Life Science Research Center, University of Oklahoma, Norman, OK, USA Background: Candida albicans is the most prevalent fungal pathogen of the human microbiota, causing infections ranging from superficial infections of the skin to life-threatening systemic infections. Due to the increasing occurrence of antibiotic-resistant C. albicans strains, new approaches to control this pathogen are needed. Photodynamic inactivation is an emerging alternative to treat infections based on the interactions between visible light and photosensitisers, in which pheophorbide a (PPA is a chlorophyll-based photosensitizer that could induce cell death after light irradiation. Due to PPA’s phototoxicity and low efficiency, the main challenge is to implement photosensitizer cell targeting and attacking. Methods: In this study, PPA was conjugated with JM-phage by EDC/NHS crosslinking. UV-Vis spectra was used to determine the optimum conjugation percentages of PPA and JM-phage complex for photodynamic inactivation. After photodynamic inactivation, the efficacy of PPA-JM-phage was assessed by performing in vitro experiments, such as MTS assay, scanning electron microscopy, measurement of dysfunctional mitochondria, ROS accumulation, S cell arrest and apoptotic pathway.Results: A single-chain variable-fragment phage (JM with high affinity to MP65 was screened from human single-fold single-chain variable-fragment libraries and designed as a binding target for C. albicans cells. Subsequently, PPa was integrated into JM phage to generate

  6. Radiation inactivation target size of rat adipocyte glucose transporters in the plasma membrane and intracellular pools

    International Nuclear Information System (INIS)

    Jacobs, D.B.; Berenski, C.J.; Spangler, R.A.; Jung, C.Y.

    1987-01-01

    The in situ assembly states of the glucose transport carrier protein in the plasma membrane and in the intracellular (microsomal) storage pool of rat adipocytes were assessed by studying radiation-induced inactivation of the D-glucose-sensitive cytochalasin B binding activities. High energy radiation inactivated the glucose-sensitive cytochalasin B binding of each of these membrane preparations by reducing the total number of the binding sites without affecting the dissociation constant. The reduction in total number of binding sites was analyzed as a function of radiation dose based on target theory, from which a radiation-sensitive mass (target size) was calculated. When the plasma membranes of insulin-treated adipocytes were used, a target size of approximately 58,000 daltons was obtained. For adipocyte microsomal membranes, we obtained target sizes of approximately 112,000 and 109,000 daltons prior to and after insulin treatment, respectively. In the case of microsomal membranes, however, inactivation data showed anomalously low radiation sensitivities at low radiation doses, which may be interpreted as indicating the presence of a radiation-sensitive inhibitor. These results suggest that the adipocyte glucose transporter occurs as a monomer in the plasma membrane while existing in the intracellular reserve pool either as a homodimer or as a stoichiometric complex with a protein of an approximately equal size

  7. Membrane-bound Na,K-ATPase: target size and radiation inactivation size of some of its enzymatic reactions

    Energy Technology Data Exchange (ETDEWEB)

    Jensen, J.; Norby, J.G.

    1988-12-05

    Frozen samples of membrane-bound pig kidney Na,K-ATPase were subjected to target size analysis by radiation inactivation with 10-MeV electrons at -15 degrees C. The various properties investigated decreased monoexponentially with radiation dose, and the decay constants, gamma, were independent of the presence of other proteins and of sucrose concentrations above 0.25 M. The temperature factor was the same as described by others. Irradiation of four proteins of known molecular mass, m, showed that gamma for protein integrity was proportional to m with a proportionality factor about 20% higher than that conventionally used. By this standard curve, glucose-6-phosphate dehydrogenase activity used as internal standard gave a radiation inactivation size of 110 +/- 5 kDa, very close to m = 104-108 kDa for the dimer, as expected. For Na+/K+-transporting ATPase the following target sizes and radiation inactivation size values were very close to m = 112 kDa for the alpha-peptide: peptide integrity of alpha, 115 kDa; unmodified binding sites for ATP and vanadate, 108 kDa; K+-activated p-nitrophenylphosphatase activity, 106 kDa. There was thus no sign of dimerization of the alpha-peptide or involvement of the beta-peptide. In contrast, optimal Na+/K+-transporting ATPase activity had a radiation inactivation size = 189 +/- 7 kDa, and total nucleotide binding capacity corresponded to 72 +/- 3 kDa. These latter results will be extended and discussed in a forthcoming paper.

  8. Membrane-bound Na,K-ATPase: target size and radiation inactivation size of some of its enzymatic reactions

    International Nuclear Information System (INIS)

    Jensen, J.; Norby, J.G.

    1988-01-01

    Frozen samples of membrane-bound pig kidney Na,K-ATPase were subjected to target size analysis by radiation inactivation with 10-MeV electrons at -15 degrees C. The various properties investigated decreased monoexponentially with radiation dose, and the decay constants, gamma, were independent of the presence of other proteins and of sucrose concentrations above 0.25 M. The temperature factor was the same as described by others. Irradiation of four proteins of known molecular mass, m, showed that gamma for protein integrity was proportional to m with a proportionality factor about 20% higher than that conventionally used. By this standard curve, glucose-6-phosphate dehydrogenase activity used as internal standard gave a radiation inactivation size of 110 +/- 5 kDa, very close to m = 104-108 kDa for the dimer, as expected. For Na+/K+-transporting ATPase the following target sizes and radiation inactivation size values were very close to m = 112 kDa for the alpha-peptide: peptide integrity of alpha, 115 kDa; unmodified binding sites for ATP and vanadate, 108 kDa; K+-activated p-nitrophenylphosphatase activity, 106 kDa. There was thus no sign of dimerization of the alpha-peptide or involvement of the beta-peptide. In contrast, optimal Na+/K+-transporting ATPase activity had a radiation inactivation size = 189 +/- 7 kDa, and total nucleotide binding capacity corresponded to 72 +/- 3 kDa. These latter results will be extended and discussed in a forthcoming paper

  9. Functional size analysis of bioactive materials by radiation inactivation

    International Nuclear Information System (INIS)

    Kume, Tamikazu

    1994-01-01

    When the research on various proteins including enzymes is carried out, first molecular weight is measured. The physical chemical methods used for measuring molecular weight cannot measure it in the state of actually acting in living bodies. Radiation inactivation method is the unique method which can measure the molecular weight of the active substances in living bodies. Paying attention to this point, recently it is attempted to measure the activity unit of enzymes, receptors and others, and to apply to the elucidation of their functions. In this report, the concept of the method of measuring molecular size based on radiation inactivation, the detailed experimental method and the points to which attention must be paid are described. Also its application to the elucidation of living body functions according to the example of the studies by the author is reported. The concept of the measurement of molecular weight by radiation inactivation is based on target theory. The preparation of samples, the effect of oxygen, radiation sources, dosimetry, irradiation temperature, internal standard process and so on are reported. The trend of the research is shown. (K.I.)

  10. Cell wall as a target for bacteria inactivation by pulsed electric fields

    Science.gov (United States)

    Pillet, Flavien; Formosa-Dague, Cécile; Baaziz, Houda; Dague, Etienne; Rols, Marie-Pierre

    2016-01-01

    The integrity and morphology of bacteria is sustained by the cell wall, the target of the main microbial inactivation processes. One promising approach to inactivation is based on the use of pulsed electric fields (PEF). The current dogma is that irreversible cell membrane electro-permeabilisation causes the death of the bacteria. However, the actual effect on the cell-wall architecture has been poorly explored. Here we combine atomic force microscopy and electron microscopy to study the cell-wall organization of living Bacillus pumilus bacteria at the nanoscale. For vegetative bacteria, exposure to PEF led to structural disorganization correlated with morphological and mechanical alterations of the cell wall. For spores, PEF exposure led to the partial destruction of coat protein nanostructures, associated with internal alterations of cortex and core. Our findings reveal for the first time that the cell wall and coat architecture are directly involved in the electro-eradication of bacteria. PMID:26830154

  11. Targeted Catalytic Inactivation of Angiotensin Converting Enzyme by Lisinopril-Coupled Transition Metal Chelates

    Science.gov (United States)

    Joyner, Jeff C.; Hocharoen, Lalintip; Cowan, J. A.

    2012-01-01

    A series of compounds that target reactive transition metal chelates to somatic Angiotensin Converting Enzyme (sACE-1) have been synthesized. Half maximal inhibitory concentrations (IC50) and rate constants for both inactivation and cleavage of full length sACE-1 have been determined and evaluated in terms of metal-chelate size, charge, reduction potential, coordination unsaturation, and coreactant selectivity. Ethylenediamine-tetraacetic acid (EDTA), nitrilotriacetic acid (NTA), 1,4,7,10-tetraazacyclo-dodecane-1,4,7,10-tetraacetic acid (DOTA), and tripeptide GGH were linked to the lysine sidechain of lisinopril by EDC/NHS coupling. The resulting amide-linked chelate-lisinopril (EDTA-lisinopril, NTA-lisinopril, DOTA-lisinopril, and GGH-lisinopril) conjugates were used to form coordination complexes with iron, cobalt, nickel and copper, such that lisinopril could mediate localization of the reactive metal chelates to sACE-1. ACE activity was assayed by monitoring cleavage of the fluorogenic substrate Mca-RPPGFSAFK(Dnp)-OH, a derivative of bradykinin, following pre-incubation with metal-chelate-lisinopril compounds. Concentration-dependent inhibition of sACE-1 by metal-chelate-lisinopril complexes revealed IC50 values ranging from 44 nM to 4,500 nM for Ni-NTA-lisinopril and Ni-DOTA-lisinopril, respectively, versus 1.9 nM for lisinopril. Stronger inhibition was correlated with smaller size and lower negative charge of the attached metal chelates. Time-dependent inactivation of sACE-1 by metal-chelate-lisinopril complexes revealed a remarkable range of catalytic activities, with second order rate constants as high as 150,000 M−1min−1 (Cu-GGH-lisinopril), while catalyst-mediated cleavage of sACE-1 typically occurred at much lower rates, indicating that inactivation arose primary from sidechain modification. Optimal inactivation of sACE-1 was observed when the reduction potential for the metal center was poised near 1000 mV, reflecting the difficulty of protein

  12. Targeted catalytic inactivation of angiotensin converting enzyme by lisinopril-coupled transition-metal chelates.

    Science.gov (United States)

    Joyner, Jeff C; Hocharoen, Lalintip; Cowan, J A

    2012-02-22

    A series of compounds that target reactive transition-metal chelates to somatic angiotensin converting enzyme (sACE-1) have been synthesized. Half-maximal inhibitory concentrations (IC(50)) and rate constants for both inactivation and cleavage of full-length sACE-1 have been determined and evaluated in terms of metal chelate size, charge, reduction potential, coordination unsaturation, and coreactant selectivity. Ethylenediaminetetraacetic acid (EDTA), nitrilotriacetic acid (NTA), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), and tripeptide GGH were linked to the lysine side chain of lisinopril by 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide hydrochloride/N-hydroxysuccinimide coupling. The resulting amide-linked chelate-lisinopril (EDTA-lisinopril, NTA-lisinopril, DOTA-lisinopril, and GGH-lisinopril) conjugates were used to form coordination complexes with iron, cobalt, nickel, and copper, such that lisinopril could mediate localization of the reactive metal chelates to sACE-1. ACE activity was assayed by monitoring cleavage of the fluorogenic substrate Mca-RPPGFSAFK(Dnp)-OH, a derivative of bradykinin, following preincubation with metal chelate-lisinopril compounds. Concentration-dependent inhibition of sACE-1 by metal chelate-lisinopril complexes revealed IC(50) values ranging from 44 to 4500 nM for Ni-NTA-lisinopril and Ni-DOTA-lisinopril, respectively, versus 1.9 nM for lisinopril. Stronger inhibition was correlated with smaller size and lower negative charge of the attached metal chelates. Time-dependent inactivation of sACE-1 by metal chelate-lisinopril complexes revealed a remarkable range of catalytic activities, with second-order rate constants as high as 150,000 M(-1) min(-1) (Cu-GGH-lisinopril), while catalyst-mediated cleavage of sACE-1 typically occurred at much lower rates, indicating that inactivation arose primarily from side chain modification. Optimal inactivation of sACE-1 was observed when the reduction potential for the

  13. Ultraviolet inactivation of avian sarcoma virus: biological and biochemical analysis

    International Nuclear Information System (INIS)

    Owada, M.; Ihara, S.; Toyoshima, K.; Kozai, Y.; Sugino, Y.

    1976-01-01

    The rate of inactivation by ultraviolet light of the focus-forming capacity of avian sarcoma virus was almost the same as that of the virus-producing capacity, measured as plaque formation. In addition, no significant difference was observed in inactivation of the transforming capacity assayed on C/BE chick embryo fibroblasts (CEF), which carry endogenous avian tumor virus DNA, and on duck embryo fibroblasts (DEF), which are known to be devoid of this DNA. All foci induced by nonirradiated virus produced infectious sarcoma virus, but some of the foci induced by uv-irradiated virus did not produce infectious virus of either transforming or transformation-defective type. The proportion of nonproducer foci was 3.4 times more in DEF than in gs - chf - CEF. RNAs extracted from uv-irradiated virions by sodium dodecyl sulfate (SDS) treatment were found to be composed of 60--70 S and 4 S RNAs by analysis in a sucrose gradient containing 0.5 percent SDS. The large RNA, however, became hydrophobic after irradiation and was sedimented with SDS by addition of one drop of saturated potassium chloride solution. This RNA was not dissociated into 30--40S components by heating at 100 0 for 45 sec, unlike 60--70 S RNA from uv-irradiated virions. After SDS--Pronase treatment, the 60--70 S RNA from uv-irradiated virions no longer had these altered characteristics. Reverse transcriptase activity with the endogenous template decreased in parallel with increase in the uv dose. The reduction rate was similar to that assayed with exogenous template or in the presence of actinomycin D. These data strongly suggest that RNA damage is not the only cause of virus inactivation by uv light

  14. Radiation inactivation analysis of chloroplast CF0-CF1 ATPase

    International Nuclear Information System (INIS)

    Wang, M.Y.; Chien, L.F.; Pan, R.L.

    1988-01-01

    Radiation inactivation technique was employed to measure the functional size of adenosine triphosphatase of spinach chloroplasts. The functional size for acid-base-induced ATP synthesis was 450 +/- 24 kilodaltons; for phenazine methosulfate-mediated ATP synthesis, 613 +/- 33 kilodaltons; and for methanol-activated ATP hydrolysis, 280 +/- 14 kilodaltons. The difference (170 +/- 57 kilodaltons) between 450 +/- 24 and 280 +/- 14 kilodaltons is explained to be the molecular mass of proton channel (coupling factor 0) across the thylakoid membrane. Our data suggest that the stoichiometry of subunits I, II, and III of coupling factor 0 is 1:2:15. Ca2+- and Mg2+-ATPase activated by methanol, heat, and trypsin digestion have a similar functional size. However, anions such as SO 3 (2-) and CO 3 (2-) increased the molecular mass for both ATPase's (except trypsin-activated Mg2+-ATPase) by 12-30%. Soluble coupling factor 1 has a larger target size than that of membrane-bound. This is interpreted as the cold effect during irradiation

  15. Inactivation and inducible oncogenic mutation of p53 in gene targeted pigs.

    Directory of Open Access Journals (Sweden)

    Simon Leuchs

    Full Text Available Mutation of the tumor suppressor p53 plays a major role in human carcinogenesis. Here we describe gene-targeted porcine mesenchymal stem cells (MSCs and live pigs carrying a latent TP53(R167H mutant allele, orthologous to oncogenic human mutant TP53(R175H and mouse Trp53(R172H, that can be activated by Cre recombination. MSCs carrying the latent TP53(R167H mutant allele were analyzed in vitro. Homozygous cells were p53 deficient, and on continued culture exhibited more rapid proliferation, anchorage independent growth, and resistance to the apoptosis-inducing chemotherapeutic drug doxorubicin, all characteristic of cellular transformation. Cre mediated recombination activated the latent TP53(R167H allele as predicted, and in homozygous cells expressed mutant p53-R167H protein at a level ten-fold greater than wild-type MSCs, consistent with the elevated levels found in human cancer cells. Gene targeted MSCs were used for nuclear transfer and fifteen viable piglets were produced carrying the latent TP53(R167H mutant allele in heterozygous form. These animals will allow study of p53 deficiency and expression of mutant p53-R167H to model human germline, or spontaneous somatic p53 mutation. This work represents the first inactivation and mutation of the gatekeeper tumor suppressor gene TP53 in a non-rodent mammal.

  16. Molecular sizes of lichen ice nucleation sites determined by gamma radiation inactivation analysis

    International Nuclear Information System (INIS)

    Kieft, T.L.; Ruscetti, T.

    1992-01-01

    It has previously been shown that some species of lichen fungi contain proteinaceous ice nuclei which are active at temperatures as warm as −2 °C. This experiment was undertaken to determine the molecular sizes of ice nuclei in the lichen fungus Rhizoplaca chrysoleuca and to compare them to bacterial ice nuclei from Pseudomonas syringae. Gamma radiation inactivation analysis was used to determine molecular weights. Radiation inactivation analysis is based on target theory, which states that the likelihood of a molecule being inactivated by gamma rays increases as its size increases. Three different sources of ice nuclei from the lichen R. chrysoleuca were tested: field-collected lichens, extract of lichen fungus, and a pure culture of the fungus R. chrysoleuca. P. syringae strain Cit7 was used as a source of bacterial ice nuclei. Samples were lyophilized, irradiated with gamma doses ranging from 0 to 10.4 Mrads, and then tested for ice nucleation activity using a droplet-freezing assay. Data for all four types of samples were in rough agreement; sizes of nucleation sites increased logarithmically with increasing temperatures of ice nucleation activity. Molecular weights of nucleation sites active between −3 and −4 °C from the bacteria and from the field-collected lichens were approximately 1.0 × 10 6 Da. Nuclei from the lichen fungus and in the lichen extract appeared to be slightly smaller but followed the same log-normal pattern with temperature of ice nucleation activity. The data for both the bacterial and lichen ice nuclei are in agreement with ice nucleation theory which states that the size of ice nucleation sites increases logarithmically as the temperature of nucleation increases linearly. This suggests that although some differences exist between bacterial and lichen ice nucleation sites, their molecular sizes are quite similar

  17. Analysis of Ribosome Inactivating Protein (RIP): A Bioinformatics Approach

    Science.gov (United States)

    Jothi, G. Edward Gnana; Majilla, G. Sahaya Jose; Subhashini, D.; Deivasigamani, B.

    2012-10-01

    In spite of the medical advances in recent years, the world is in need of different sources to encounter certain health issues.Ribosome Inactivating Proteins (RIPs) were found to be one among them. In order to get easy access about RIPs, there is a need to analyse RIPs towards constructing a database on RIPs. Also, multiple sequence alignment was done towards screening for homologues of significant RIPs from rare sources against RIPs from easily available sources in terms of similarity. Protein sequences were retrieved from SWISS-PROT and are further analysed using pair wise and multiple sequence alignment.Analysis shows that, 151 RIPs have been characterized to date. Amongst them, there are 87 type I, 37 type II, 1 type III and 25 unknown RIPs. The sequence length information of various RIPs about the availability of full or partial sequence was also found. The multiple sequence alignment of 37 type I RIP using the online server Multalin, indicates the presence of 20 conserved residues. Pairwise alignment and multiple sequence alignment of certain selected RIPs in two groups namely Group I and Group II were carried out and the consensus level was found to be 98%, 98% and 90% respectively.

  18. Thermal inactivation of enzymes and pathogens in biosamples for MS analysis.

    Science.gov (United States)

    Ahnoff, Martin; Cazares, Lisa H; Sköld, Karl

    2015-01-01

    Protein denaturation is the common basis for enzyme inactivation and inactivation of pathogens, necessary for preservation and safe handling of biosamples for downstream analysis. While heat-stabilization technology has been used in proteomic and peptidomic research since its introduction in 2009, the advantages of using the technique for simultaneous pathogen inactivation have only recently been addressed. The time required for enzyme inactivation by heat (≈1 min) is short compared with chemical treatments, and inactivation is irreversible in contrast to freezing. Heat stabilization thus facilitates mass spectrometric studies of biomolecules with a fast conversion rate, and expands the chemical space of potential biomarkers to include more short-lived entities, such as phosphorylated proteins, in tissue samples as well as whole-blood (dried blood sample) samples.

  19. Nanoscale Structural and Mechanical Analysis of Bacillus anthracis Spores Inactivated with Rapid Dry Heating

    Science.gov (United States)

    Felker, Daniel L.; Burggraf, Larry W.

    2014-01-01

    Effective killing of Bacillus anthracis spores is of paramount importance to antibioterrorism, food safety, environmental protection, and the medical device industry. Thus, a deeper understanding of the mechanisms of spore resistance and inactivation is highly desired for developing new strategies or improving the known methods for spore destruction. Previous studies have shown that spore inactivation mechanisms differ considerably depending upon the killing agents, such as heat (wet heat, dry heat), UV, ionizing radiation, and chemicals. It is believed that wet heat kills spores by inactivating critical enzymes, while dry heat kills spores by damaging their DNA. Many studies have focused on the biochemical aspects of spore inactivation by dry heat; few have investigated structural damages and changes in spore mechanical properties. In this study, we have inactivated Bacillus anthracis spores with rapid dry heating and performed nanoscale topographical and mechanical analysis of inactivated spores using atomic force microscopy (AFM). Our results revealed significant changes in spore morphology and nanomechanical properties after heat inactivation. In addition, we also found that these changes were different under different heating conditions that produced similar inactivation probabilities (high temperature for short exposure time versus low temperature for long exposure time). We attributed the differences to the differential thermal and mechanical stresses in the spore. The buildup of internal thermal and mechanical stresses may become prominent only in ultrafast, high-temperature heat inactivation when the experimental timescale is too short for heat-generated vapor to efficiently escape from the spore. Our results thus provide direct, visual evidences of the importance of thermal stresses and heat and mass transfer to spore inactivation by very rapid dry heating. PMID:24375142

  20. Expression analysis for inverted effects of serotonin transporter inactivation

    International Nuclear Information System (INIS)

    Ichikawa, Manabu; Okamura-Oho, Yuko; Shimokawa, Kazuro; Kondo, Shinji; Nakamura, Sakiko; Yokota, Hideo; Himeno, Ryutaro; Lesch, Klaus-Peter; Hayashizaki, Yoshihide

    2008-01-01

    Inactivation of serotonin transporter (HTT) by pharmacologically in the neonate or genetically increases risk for depression in adulthood, whereas pharmacological inhibition of HTT ameliorates symptoms in depressed patients. The differing role of HTT function during early development and in adult brain plasticity in causing or reversing depression remains an unexplained paradox. To address this we profiled the gene expression of adult Htt knockout (Htt KO) mice and HTT inhibitor-treated mice. Inverted profile changes between the two experimental conditions were seen in 30 genes. Consistent results of the upstream regulatory element search and the co-localization search of these genes indicated that the regulation may be executed by Pax5, Pax7 and Gata3, known to be involved in the survival, proliferation, and migration of serotonergic neurons in the developing brain, and these factors are supposed to keep functioning to regulate downstream genes related to serotonin system in the adult brain

  1. Quantitative analysis of wet-heat inactivation in bovine spongiform encephalopathy

    International Nuclear Information System (INIS)

    Matsuura, Yuichi; Ishikawa, Yukiko; Bo, Xiao; Murayama, Yuichi; Yokoyama, Takashi; Somerville, Robert A.; Kitamoto, Tetsuyuki; Mohri, Shirou

    2013-01-01

    Highlights: ► We quantitatively analyzed wet-heat inactivation of the BSE agent. ► Infectivity of the BSE macerate did not survive 155 °C wet-heat treatment. ► Once the sample was dehydrated, infectivity was observed even at 170 °C. ► A quantitative PMCA assay was used to evaluate the degree of BSE inactivation. - Abstract: The bovine spongiform encephalopathy (BSE) agent is resistant to conventional microbial inactivation procedures and thus threatens the safety of cattle products and by-products. To obtain information necessary to assess BSE inactivation, we performed quantitative analysis of wet-heat inactivation of infectivity in BSE-infected cattle spinal cords. Using a highly sensitive bioassay, we found that infectivity in BSE cattle macerates fell with increase in temperatures from 133 °C to 150 °C and was not detected in the samples subjected to temperatures above 155 °C. In dry cattle tissues, infectivity was detected even at 170 °C. Thus, BSE infectivity reduces with increase in wet-heat temperatures but is less affected when tissues are dehydrated prior to the wet-heat treatment. The results of the quantitative protein misfolding cyclic amplification assay also demonstrated that the level of the protease-resistant prion protein fell below the bioassay detection limit by wet-heat at 155 °C and higher and could help assess BSE inactivation. Our results show that BSE infectivity is strongly resistant to wet-heat inactivation and that it is necessary to pay attention to BSE decontamination in recycled cattle by-products

  2. Quantitative analysis of wet-heat inactivation in bovine spongiform encephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Matsuura, Yuichi; Ishikawa, Yukiko; Bo, Xiao; Murayama, Yuichi; Yokoyama, Takashi [Prion Disease Research Center, National Institute of Animal Health, 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0856 (Japan); Somerville, Robert A. [The Roslin Institute and Royal (Dick) School of Veterinary Studies, Roslin, Midlothian, EH25 9PS (United Kingdom); Kitamoto, Tetsuyuki [Division of CJD Science and Technology, Department of Prion Research, Center for Translational and Advanced Animal Research on Human Diseases, Tohoku University Graduate School of Medicine, 2-1 Seiryo, Aoba, Sendai 980-8575 (Japan); Mohri, Shirou, E-mail: shirou@affrc.go.jp [Prion Disease Research Center, National Institute of Animal Health, 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0856 (Japan)

    2013-03-01

    Highlights: ► We quantitatively analyzed wet-heat inactivation of the BSE agent. ► Infectivity of the BSE macerate did not survive 155 °C wet-heat treatment. ► Once the sample was dehydrated, infectivity was observed even at 170 °C. ► A quantitative PMCA assay was used to evaluate the degree of BSE inactivation. - Abstract: The bovine spongiform encephalopathy (BSE) agent is resistant to conventional microbial inactivation procedures and thus threatens the safety of cattle products and by-products. To obtain information necessary to assess BSE inactivation, we performed quantitative analysis of wet-heat inactivation of infectivity in BSE-infected cattle spinal cords. Using a highly sensitive bioassay, we found that infectivity in BSE cattle macerates fell with increase in temperatures from 133 °C to 150 °C and was not detected in the samples subjected to temperatures above 155 °C. In dry cattle tissues, infectivity was detected even at 170 °C. Thus, BSE infectivity reduces with increase in wet-heat temperatures but is less affected when tissues are dehydrated prior to the wet-heat treatment. The results of the quantitative protein misfolding cyclic amplification assay also demonstrated that the level of the protease-resistant prion protein fell below the bioassay detection limit by wet-heat at 155 °C and higher and could help assess BSE inactivation. Our results show that BSE infectivity is strongly resistant to wet-heat inactivation and that it is necessary to pay attention to BSE decontamination in recycled cattle by-products.

  3. An evolved ribosome-inactivating protein targets and kills human melanoma cells in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Green David E

    2010-02-01

    Full Text Available Abstract Background Few treatment options exist for patients with metastatic melanoma, resulting in poor prognosis. One standard treatment, dacarbazine (DTIC, shows low response rates ranging from 15 to 25 percent with an 8-month median survival time. The development of targeted therapeutics with novel mechanisms of action may improve patient outcome. Ribosome-inactivating proteins (RIPs such as Shiga-like Toxin 1 (SLT-1 represent powerful scaffolds for developing selective anticancer agents. Here we report the discovery and properties of a single chain ribosome-inactivating protein (scRIP derived from the cytotoxic A subunit of SLT-1 (SLT-1A, harboring the 7-amino acid peptide insertion IYSNKLM (termed SLT-1AIYSNKLM allowing the toxin variant to selectively target and kill human melanoma cells. Results SLT-1AIYSNKLM was able to kill 7 of 8 human melanoma cell lines. This scRIP binds to 518-A2 human melanoma cells with a dissociation constant of 18 nM, resulting in the blockage of protein synthesis and apoptosis in such cells. Biodistribution and imaging studies of radiolabeled SLT-1AIYSNKLM administered intravenously into SCID mice bearing a human melanoma xenograft indicate that SLT-1AIYSNKLM readily accumulates at the tumor site as opposed to non-target tissues. Furthermore, the co-administration of SLT-1AIYSNKLM with DTIC resulted in tumor regression and greatly increased survival in this mouse xenograft model in comparison to DTIC or SLT-1AIYSNKLM treatment alone (115 day median survival versus 46 and 47 days respectively; P values IYSNKLM is stable in serum and its intravenous administration resulted in modest immune responses following repeated injections in CD1 mice. Conclusions These results demonstrate that the evolution of a scRIP template can lead to the discovery of novel cancer cell-targeted compounds and in the case of SLT-1AIYSNKLM can specifically kill human melanoma cells in vitro and in vivo.

  4. Effect of ohmic heating of soymilk on urease inactivation and kinetic analysis in holding time.

    Science.gov (United States)

    Li, Fa-De; Chen, Chen; Ren, Jie; Wang, Ranran; Wu, Peng

    2015-02-01

    To verify the effect of the ohmic heating on the urease activity in the soymilk, the ohmic heating methods with the different electrical field conditions (the frequency and the voltage ranging from 50 to 10 kHz and from 160 to 220 V, respectively) were employed. The results showed that if the value of the urease activity measured with the quantitative spectrophotometry method was lower than 16.8 IU, the urease activity measured with the qualitative method was negative. The urease activity of the sample ohmically heated was significantly lower than that of the sample conventionally heated (P urease inactivation. In addition, the inactivation kinetics of the urease in the soymilk could be described with a biphasic model during holding time at a target temperature. Thus, it was concluded that the urease in the soymilk would contain 2 isoenzymes, one is the thermolabile fraction, the other the thermostable fraction, and that the thermostable isoenzyme could not be completely inactivated when the holding time increased, whether the soymilk was cooked with the conventional method or with the ohmic heating method. Therefore, the electric field had no effect on the inactivation of the thermostable isoenzyme of the urease. © 2015 Institute of Food Technologists®

  5. Hydrogen peroxide (H2O2) irreversibly inactivates creatine kinase from Pelodiscus sinensis by targeting the active site cysteine.

    Science.gov (United States)

    Wang, Wei; Lee, Jinhyuk; Hao, Hao; Park, Yong-Doo; Qian, Guo-Ying

    2017-12-01

    Creatine kinase (EC 2.7.3.2, CK) plays an important role in cellular energy metabolism and homeostasis by catalysing the transfer of phosphate between ATP and creatine phosphate. In this study, we investigated the effects of H 2 O 2 on PSCKM (muscle type creatine kinase from Pelodiscus sinensis) by the integrating method between enzyme kinetics and docking simulations. We found that H 2 O 2 strongly inactivated PSCKM (IC 50 =0.25mM) in a first-order kinetic process, and targeted the active site cysteine directly. A conformational study showed that H 2 O 2 did not induce the tertiary structural changes in PSCKM with no extensive exposure of hydrophobic surfaces. Sequential docking simulations between PSCKM and H 2 O 2 indicated that H 2 O 2 interacts with the ADP binding region of the active site, consistent with experimental results that demonstrated H 2 O 2 -induced inactivation. Our study demonstrates the effect of H 2 O 2 on PSCKM enzymatic function and unfolding, and provides important insight into the changes undergone by this central metabolic enzyme in ectothermic animals in response to the environment. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Immunogenicity of two adjuvant formulations of an inactivated African horse sickness vaccine in guinea-pigs and target animals

    Directory of Open Access Journals (Sweden)

    Gaetano Federico Ronchi

    2012-03-01

    Full Text Available Monovalent, inactivated and adjuvanted vaccines against African horse sickness, prepared with serotypes 5 and 9, were tested on guinea-pigs to select the formulation that offered the greatest immunity. The final formulation of the vaccines took into account the immune response in the guinea-pig and the inflammatory properties of two types of adjuvant previously tested on target animals. A pilot study was subsequently conducted on horses using a vaccine prepared with serotype 9. The vaccine stimulated neutralising antibodies from the first administration and, after the booster dose, 28 days later; high antibody levels were recorded for at least 10 months. The guinea-pig appears to be a useful laboratory model for the evaluation of the antigenic properties of African horse sickness vaccines.

  7. Radiation inactivation analysis of assimilatory NADH:nitrate reductase. Apparent functional sizes of partial activities associated with intact and proteolytically modified enzyme

    International Nuclear Information System (INIS)

    Solomonson, L.P.; McCreery, M.J.; Kay, C.J.; Barber, M.J.

    1987-01-01

    Recently we demonstrated that target sizes for the partial activities of nitrate reductase were considerably smaller than the 100-kDa subunit which corresponded to the target size of the full (physiologic) activity NADH:nitrate reductase. These results suggested that the partial activities resided on functionally independent domains and that radiation inactivation may be due to localized rather than extensive damage to protein structure. The present study extends these observations and addresses several associated questions. Monophasic plots were observed over a wide range of radiation doses, suggesting a single activity component in each case. No apparent differences were observed over a 10-fold range of concentration for each substrate, suggesting that the observed slopes were not due to marked changes in Km values. Apparent target sizes estimated for partial activities associated with native enzyme and with limited proteolysis products of native enzyme suggested that the functional size obtained by radiation inactivation analysis is independent of the size of the polypeptide chain. The presence of free radical scavengers during irradiation reduced the apparent target size of both the physiologic and partial activities by an amount ranging from 24 to 43%, suggesting that a free radical mechanism is at least partially responsible for the inactivation. Immunoblot analysis of nitrate reductase irradiated in the presence of free radical scavengers revealed formation of distinct bands at 90, 75, and 40 kDa with increasing doses of irradiation rather than complete destruction of the polypeptide chain

  8. Inactivation of Pol θ and C-NHEJ eliminates off-target integration of exogenous DNA.

    Science.gov (United States)

    Zelensky, Alex N; Schimmel, Joost; Kool, Hanneke; Kanaar, Roland; Tijsterman, Marcel

    2017-07-07

    Off-target or random integration of exogenous DNA hampers precise genomic engineering and presents a safety risk in clinical gene therapy strategies. Genetic definition of random integration has been lacking for decades. Here, we show that the A-family DNA polymerase θ (Pol θ) promotes random integration, while canonical non-homologous DNA end joining plays a secondary role; cells double deficient for polymerase θ and canonical non-homologous DNA end joining are devoid of any integration events, demonstrating that these two mechanisms define random integration. In contrast, homologous recombination is not reduced in these cells and gene targeting is improved to 100% efficiency. Such complete reversal of integration outcome, from predominately random integration to exclusively gene targeting, provides a rational way forward to improve the efficacy and safety of DNA delivery and gene correction approaches.Random off-target integration events can impair precise gene targeting and poses a safety risk for gene therapy. Here the authors show that repression of polymerase θ and classical non-homologous recombination eliminates random integration.

  9. Pantothenamides are potent, on-target inhibitors of Plasmodium falciparum growth when serum pantetheinase is inactivated.

    Directory of Open Access Journals (Sweden)

    Christina Spry

    Full Text Available Growth of the virulent human malaria parasite Plasmodium falciparum is dependent on an extracellular supply of pantothenate (vitamin B(5 and is susceptible to inhibition by pantothenate analogues that hinder pantothenate utilization. In this study, on the hunt for pantothenate analogues with increased potency relative to those reported previously, we screened a series of pantothenamides (amide analogues of pantothenate against P. falciparum and show for the first time that analogues of this type possess antiplasmodial activity. Although the active pantothenamides in this series exhibit only modest potency under standard in vitro culture conditions, we show that the potency of pantothenamides is selectively enhanced when the parasite culture medium is pre-incubated at 37°C for a prolonged period. We present evidence that this finding is linked to the presence in Albumax II (a serum-substitute routinely used for in vitro cultivation of P. falciparum of pantetheinase activity: the activity of an enzyme that hydrolyzes the pantothenate metabolite pantetheine, for which pantothenamides also serve as substrates. Pantetheinase activity, and thereby pantothenamide degradation, is reduced following incubation of Albumax II-containing culture medium for a prolonged period at 37°C, revealing the true, sub-micromolar potency of pantothenamides. Importantly we show that the potent antiplasmodial effect of pantothenamides is attenuated with pantothenate, consistent with the compounds inhibiting parasite proliferation specifically by inhibiting pantothenate and/or CoA utilization. Additionally, we show that the pantothenamides interact with P. falciparum pantothenate kinase, the first enzyme involved in converting pantothenate to coenzyme A. This is the first demonstration of on-target antiplasmodial pantothenate analogues with sub-micromolar potency, and highlights the potential of pantetheinase-resistant pantothenamides as antimalarial agents.

  10. Functional and physical molecular size of the chicken hepatic lectin determined by radiation inactivation and sedimentation equilibrium analysis

    International Nuclear Information System (INIS)

    Steer, C.J.; Osborne, J.C. Jr.; Kempner, E.S.

    1990-01-01

    Radiation inactivation and sedimentation equilibrium analysis were used to determine the functional and physical size of the chicken hepatic membrane receptor that binds N-acetylglucosamine-terminated glycoproteins. Purified plasma membranes from chicken liver were irradiated with high energy electrons and assayed for 125I-agalactoorosomucoid binding. Increasing the dose of ionizing radiation resulted in a monoexponential decay in binding activity due to a progressive loss of binding sites. The molecular mass of the chicken lectin, determined in situ by target analysis, was 69,000 +/- 9,000 Da. When the same irradiated membranes were solubilized in Brij 58 and assayed, the binding protein exhibited a target size of 62,000 +/- 4,000 Da; in Triton X-100, the functional size of the receptor was 85,000 +/- 10,000 Da. Sedimentation equilibrium measurements of the purified binding protein yielded a lower limit molecular weight of 79,000 +/- 7,000. However, the solubilized lectin was detected as a heterogeneous population of oligomers with molecular weights as high as 450,000. Addition of calcium or calcium plus N-acetylglucosamine decreased the higher molecular weight species, but the lower limit molecular weights remained invariant. Similar results were determined when the chicken lectin was solubilized in Brij 58, C12E9, or 3-[(3-cholamidopropyl)dimethylammonio]-1-propane-sulfonic acid (CHAPS). Results from the present study suggest that in the plasma membrane, the functional species of the chicken hepatic lectin exists as a trimer. However, in detergent solution, the purified receptor forms a heterogeneous population of irreversible oligomers that exhibit binding activity proportional to size

  11. Advanced Analysis to Distinguish between Physical Decrease and Inactivation of Viable Phages in Aerosol by Quantitating Phage-Specific Particles.

    Science.gov (United States)

    Shimasaki, Noriko; Nojima, Yasuhiro; Sakakibara, Masaya; Kikuno, Ritsuko; Iizuka, Chiori; Okaue, Akira; Okuda, Shunji; Shinohara, Katsuaki

    2018-01-01

     Recent studies have investigated the efficacy of air-cleaning products against pathogens in the air. A standard method to evaluate the reduction in airborne viruses caused by an air cleaner has been established using a safe bacteriophage instead of pathogenic viruses; the reduction in airborne viruses is determined by counting the number of viable airborne phages by culture, after operating the air cleaner. The reduction in the number of viable airborne phages could be because of "physical decrease" or "inactivation". Therefore, to understand the mechanism of reduction correctly, an analysis is required to distinguish between physical decrease and inactivation. The purpose of this study was to design an analysis to distinguish between the physical decrease and inactivation of viable phi-X174 phages in aerosols. We established a suitable polymerase chain reaction (PCR) system by selecting an appropriate primer-probe set for PCR and validating the sensitivity, linearity, and specificity of the primer-probe set to robustly quantify phi-X174-specific airborne particles. Using this quantitative PCR system and culture assay, we performed a behavior analysis of the phage aerosol in a small chamber (1 m 3 ) at different levels of humidity, as humidity is known to affect the number of viable airborne phages. The results revealed that the reduction in the number of viable airborne phages was caused not only by physical decrease but also by inactivation under particular levels of humidity. Our study could provide an advanced analysis to differentiate between the physical decrease and inactivation of viable airborne phages.

  12. Inactivation of Phaeodactylum tricornutum urease gene using transcription activator-like effector nuclease-based targeted mutagenesis.

    Science.gov (United States)

    Weyman, Philip D; Beeri, Karen; Lefebvre, Stephane C; Rivera, Josefa; McCarthy, James K; Heuberger, Adam L; Peers, Graham; Allen, Andrew E; Dupont, Christopher L

    2015-05-01

    Diatoms are unicellular photosynthetic algae with promise for green production of fuels and other chemicals. Recent genome-editing techniques have greatly improved the potential of many eukaryotic genetic systems, including diatoms, to enable knowledge-based studies and bioengineering. Using a new technique, transcription activator-like effector nucleases (TALENs), the gene encoding the urease enzyme in the model diatom, Phaeodactylum tricornutum, was targeted for interruption. The knockout cassette was identified within the urease gene by PCR and Southern blot analyses of genomic DNA. The lack of urease protein was confirmed by Western blot analyses in mutant cell lines that were unable to grow on urea as the sole nitrogen source. Untargeted metabolomic analysis revealed a build-up of urea, arginine and ornithine in the urease knockout lines. All three intermediate metabolites are upstream of the urease reaction within the urea cycle, suggesting a disruption of the cycle despite urea production. Numerous high carbon metabolites were enriched in the mutant, implying a breakdown of cellular C and N repartitioning. The presented method improves the molecular toolkit for diatoms and clarifies the role of urease in the urea cycle. © 2014 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  13. High pressure inactivation of relevant target microorganisms in poultry meat products and the evaluation of pressure-induced protein denaturation of marinated poultry under different high pressure treatments

    Science.gov (United States)

    Schmidgall, Johanna; Hertel, Christian; Bindrich, Ute; Heinz, Volker; Toepfl, Stefan

    2011-03-01

    In this study, the possibility of extending shelf life of marinated poultry meat products by high pressure processing was evaluated. Relevant spoilage and pathogenic strains were selected and used as target microorganisms (MOs) for challenge experiments. Meat and brine were inoculated with MOs and treated at 450 MPa, 4 °C for 3 min. The results of inactivation show a decreasing pressure tolerance in the series Lactobacillus > Arcobacter > Carnobacterium > Bacillus cereus > Brochothrix thermosphacta > Listeria monocytogenes. Leuconostoc gelidum exhibited the highest pressure tolerance in meat. A protective effect of poultry meat was found for L. sakei and L. gelidum. In parallel, the influence of different marinade formulations (pH, carbonates, citrates) on protein structure changes during a pressure treatment was investigated. Addition of sodium carbonate shows a protection against denaturation of myofibrillar proteins and provides a maximum water-holding capacity. Caustic marinades allowed a higher retention of product characteristics than low-pH marinades.

  14. Independent clonal origin of multiple uterine leiomyomas that was determined by X chromosome inactivation and microsatellite analysis

    DEFF Research Database (Denmark)

    Canevari, Renata A; Pontes, Anaglória; Rosa, Fabíola E

    2005-01-01

    OBJECTIVE: In an attempt to clarify the clonality and genetic relationships that are involved in the tumorigenesis of uterine leiomyomas, we used a total of 43 multiple leiomyomas from 14 patients and analyzed the allelic status with 15 microsatellite markers and X chromosome inactivation analysis...... of the 9 of 12 informative patients; different inactivation patterns were observed in 3 cases. CONCLUSION: Our data support the concept that uterine leiomyomas are derived from a single cell but are generated independently in the uterus. Loss of heterozygosity findings at 7p22-15 are consistent...... with previous data that suggested the relevance of chromosomal aberrations at 7p that were involved in individual uterine leiomyomas....

  15. Uncertainties in thick-target PIXE analysis

    International Nuclear Information System (INIS)

    Campbell, J.L.; Cookson, J.A.; Paul, H.

    1983-01-01

    Thick-target PIXE analysis insolves uncertainties arising from the calculation of thick-target X-ray production in addition to the usual PIXE uncertainties. The calculation demands knowledge of ionization cross-sections, stopping powers and photon attenuation coefficients. Information on these is reviewed critically and a computational method is used to estimate the uncertainties transmitted from this data base into results of thick-target PIXE analyses with reference to particular specimen types using beams of 2-3 MeV protons. A detailed assessment of the accuracy of thick-target PIXE is presented. (orig.)

  16. Detailed analysis of the cell-inactivation mechanism by accelerated protons and light ions

    Czech Academy of Sciences Publication Activity Database

    Kundrát, Pavel

    2006-01-01

    Roč. 51, - (2006), s. 1185-1199 ISSN 0031-9155 R&D Projects: GA ČR GA202/05/2728 Institutional research plan: CEZ:AV0Z10100502 Keywords : biological effects of ionizing particles * cell inactivation * modelling * protons * light ions * hadron radiotherapy Subject RIV: BF - Elementary Particles and High Energy Physics Impact factor: 2.873, year: 2006

  17. Kinetic Analysis of Guanidine Hydrochloride Inactivation of β-Galactosidase in the Presence of Galactose

    Directory of Open Access Journals (Sweden)

    Charles O. Nwamba

    2012-01-01

    Full Text Available Inactivation of purified β-Galactosidase was done with GdnHCl in the absence and presence of varying [galactose] at 50°C and at pH 4.5. Lineweaver-Burk plots of initial velocity data, in the presence and absence of guanidine hydrochloride (GdnHCl and galactose, were used to determine the relevant and max values, with p-nitrophenyl β-D-galactopyranoside (pNPG as substrate, S. Plots of ln([]∞−[] against time in the presence of GdnHCl yielded the inactivation rate constant, A. Plots of A versus [S] at different galactose concentrations were straight lines that became increasingly less steep as the [galactose] increased, showing that A was dependent on [S]. Slopes and intercepts of the 1/[]∞ versus 1/[] yielded +0 and ′+0, the microscopic rate constants for the free enzyme and the enzyme-substrate complex, respectively. Plots of +0 and ′+0 versus [galactose] showed that galactose protected the free enzyme as well as the enzyme-substrate complex (only at the lowest and highest [galactose] against GdnHCl inactivation. In the absence of galactose, GdnHCl exhibited some degree of non-competitive inhibition. In the presence of GdnHCl, galactose exhibited competitive inhibition at the lower [galactose] of 5 mM which changed to non-competitive as the [galactose] increased. The implications of our findings are further discussed.

  18. Analysis of laser therapy effects in Sporothrix schenckii inactivation in vivo

    Directory of Open Access Journals (Sweden)

    Gunther Monteiro de Paula Guirado

    2018-05-01

    Full Text Available Abstract Introduction Sporotrichosis is a common disease in tropical regions, caused by the fungus Sporothrix schenckii, affecting mainly rural workers and in direct contact with animals. Although treatment by indiscriminate use of oral antifungal drugs gives rise resistant isolates, leading to therapeutic failures and no remission of the disease. To evaluate the effectiveness of red low-power laser photobiomodulation in inactivation of S. schenckii infection induced in rodents. Methods Subcutaneously inoculation (2x103 S. schenckii/ml, 0.2 ml suspension in the left footpad, in 27 mice divided into: control (n = 6, inoculated, without irradiation: early stage (not inoculated = 1th biopsy; intermediate (9 weeks of evolution = 2nd biopsy; final (21 weeks of evolution = 3th biopsy. Treated (n = 21, inoculated and irradiated: early (13 weeks of evolution, 4 weeks after first irradiation = 4th biopsy, intermediate (17 weeks of evolution, 8 weeks after first irradiation = 5th biopsy, final (21 weeks of evolution, 12 weeks after first irradiation = 6th biopsy. Serial irradiation with biopsies occurred every 30 days during each month, for three months. At the end of testing, the mice were euthanized, and histological analyzes of biopsies were performed. Results Each laser treatment session showed an inactivation of S. schenckii in treated animals compared to controls, with a regression of pseudoepitheliomatous hyperplasia, chronic inflammation, neutrophils, granulomas, giant mononuclear cells and steroid corpuscles. Conclusion The laser photobiomodulation was effective on S. schenckii inactivation, appearing to be an interesting therapeutic option in infections caused by this organism.

  19. Genetic inactivation of mitochondria-targeted redox enzyme p66ShcA preserves neuronal viability and mitochondrial integrity in response to oxidative challenges

    Directory of Open Access Journals (Sweden)

    Michael eForte

    2012-07-01

    Full Text Available Mitochondria are essential to neuronal viability and function due to their roles in ATP production, intracellular calcium regulation, and activation of apoptotic pathways. Accordingly, mitochondrial dysfunction has been indicated in a wide variety of neurodegenerative diseases, including Alzheimer’s disease, Huntington’s disease, amyotrophic lateral sclerosis, stroke and multiple sclerosis (MS. Recent evidence points to the permeability transition pore (PTP as a key player in mitochondrial dysfunction in these diseases, in which pathologic opening leads to mitochondrial swelling, rupture, release of cytochrome c, and neuronal death. Reactive oxygen species (ROS, which are inducers of PTP opening, have been prominently implicated in the progression of many of these neurodegenerative diseases. In this context, inactivation of a mitochondria-targeted redox enzyme p66ShcA (p66 has been recently shown to prevent the neuronal cell death leading to axonal severing in the murine model of MS, experimental autoimmune encephalomyelitis (EAE. To further characterize the response of neurons lacking p66, we assessed their reaction to treatment with oxidative stressors implicated in neurodegenerative pathways. Specifically, p66-knockout (p66-KO and wild-type (WT neurons were treated with hydrogen peroxide (H2O2 and nitric oxide (NO, and assessed for cell viability and changes in mitochondrial properties, including morphology and ROS production. The results showed that p66-KO neurons had greater survival following treatment with oxidative stressors and generated less ROS when compared to WT neurons. Correspondingly, mitochondria in p66-KO neurons showed diminished morphological changes in response to these challenges. Overall, these findings highlight the importance of developing mitochondria-targeted therapeutics for neurodegenerative disorders, and emphasize p66, mitochondrial ROS, and the PTP as key targets for maintaining mitochondrial and neuronal

  20. Characterization of X chromosome inactivation using integrated analysis of whole-exome and mRNA sequencing.

    Directory of Open Access Journals (Sweden)

    Szabolcs Szelinger

    Full Text Available In females, X chromosome inactivation (XCI is an epigenetic, gene dosage compensatory mechanism by inactivation of one copy of X in cells. Random XCI of one of the parental chromosomes results in an approximately equal proportion of cells expressing alleles from either the maternally or paternally inherited active X, and is defined by the XCI ratio. Skewed XCI ratio is suggestive of non-random inactivation, which can play an important role in X-linked genetic conditions. Current methods rely on indirect, semi-quantitative DNA methylation-based assay to estimate XCI ratio. Here we report a direct approach to estimate XCI ratio by integrated, family-trio based whole-exome and mRNA sequencing using phase-by-transmission of alleles coupled with allele-specific expression analysis. We applied this method to in silico data and to a clinical patient with mild cognitive impairment but no clear diagnosis or understanding molecular mechanism underlying the phenotype. Simulation showed that phased and unphased heterozygous allele expression can be used to estimate XCI ratio. Segregation analysis of the patient's exome uncovered a de novo, interstitial, 1.7 Mb deletion on Xp22.31 that originated on the paternally inherited X and previously been associated with heterogeneous, neurological phenotype. Phased, allelic expression data suggested an 83∶20 moderately skewed XCI that favored the expression of the maternally inherited, cytogenetically normal X and suggested that the deleterious affect of the de novo event on the paternal copy may be offset by skewed XCI that favors expression of the wild-type X. This study shows the utility of integrated sequencing approach in XCI ratio estimation.

  1. Targeted inactivation of the murine Abca3 gene leads to respiratory failure in newborns with defective lamellar bodies

    International Nuclear Information System (INIS)

    Hammel, Markus; Michel, Geert; Hoefer, Christina; Klaften, Matthias; Mueller-Hoecker, Josef; Angelis, Martin Hrabe de; Holzinger, Andreas

    2007-01-01

    Mutations in the human ABCA3 gene, encoding an ABC-transporter, are associated with respiratory failure in newborns and pediatric interstitial lung disease. In order to study disease mechanisms, a transgenic mouse model with a disrupted Abca3 gene was generated by targeting embryonic stem cells. While heterozygous animals developed normally and were fertile, individuals homozygous for the altered allele (Abca3-/-) died within one hour after birth from respiratory failure, ABCA3 protein being undetectable. Abca3-/- newborns showed atelectasis of the lung in comparison to a normal gas content in unaffected or heterozygous littermates. Electron microscopy demonstrated the absence of normal lamellar bodies in type II pneumocytes. Instead, condensed structures with apparent absence of lipid content were found. We conclude that ABCA3 is required for the formation of lamellar bodies and lung surfactant function. The phenotype of respiratory failure immediately after birth corresponds to the clinical course of severe ABCA3 mutations in human newborns

  2. Microsatellite instability in pediatric high grade glioma is associated with genomic profile and differential target gene inactivation.

    Directory of Open Access Journals (Sweden)

    Marta Viana-Pereira

    Full Text Available High grade gliomas (HGG are one of the leading causes of cancer-related deaths in children, and there is increasing evidence that pediatric HGG may harbor distinct molecular characteristics compared to adult tumors. We have sought to clarify the role of microsatellite instability (MSI in pediatric versus adult HGG. MSI status was determined in 144 patients (71 pediatric and 73 adults using a well established panel of five quasimonomorphic mononucleotide repeat markers. Expression of MLH1, MSH2, MSH6 and PMS2 was determined by immunohistochemistry, MLH1 was assessed for mutations by direct sequencing and promoter methylation using MS-PCR. DNA copy number profiles were derived using array CGH, and mutations in eighteen MSI target genes studied by multiplex PCR and genotyping. MSI was found in 14/71 (19.7% pediatric cases, significantly more than observed in adults (5/73, 6.8%; p = 0.02, Chi-square test. MLH1 expression was downregulated in 10/13 cases, however no mutations or promoter methylation were found. MSH6 was absent in one pediatric MSI-High tumor, consistent with an inherited mismatch repair deficiency associated with germline MSH6 mutation. MSI was classed as Type A, and associated with a remarkably stable genomic profile. Of the eighteen classic MSI target genes, we identified mutations only in MSH6 and DNAPKcs and described a polymorphism in MRE11 without apparent functional consequences in DNA double strand break detection and repair. This study thus provides evidence for a potential novel molecular pathway in a proportion of gliomas associated with the presence of MSI.

  3. Correlates of protection for inactivated enterovirus 71 vaccine: the analysis of immunological surrogate endpoints.

    Science.gov (United States)

    Zhu, Wenbo; Jin, Pengfei; Li, Jing-Xin; Zhu, Feng-Cai; Liu, Pei

    2017-09-01

    Inactivated Enterovirus 71 (EV71) vaccines showed significant efficacy against the diseases associated with EV71 and a neutralizing antibody (NTAb) titer of 1:16-1:32 was suggested as the correlates of the vaccine protection. This paper aims to further estimate the immunological surrogate endpoints for the protection of inactivated EV71 vaccines and the effect factors. Pre-vaccination NTAb against EV71 at baseline (day 0), post-vaccination NTAb against EV71 at day 56, and the occurrence of laboratory-confirmed EV71-associated diseases during a 24-months follow-up period were collected from a phase 3 efficacy trial of an inactivated EV71 vaccine. We used the mixed-scaled logit model and the absolute sigmoid function by some extensions in continuous models to estimate the immunological surrogate endpoint for the EV71 vaccine protection, respectively. For children with a negative baseline of EV71 NTAb titers, an antibody level of 26.6 U/ml (1:30) was estimated to provide at least a 50% protection for 12 months, and an antibody level of 36.2 U/ml (1:42) may be needed to achieve a 50% protective level of the population for 24 months. Both the pre-vaccination NTAb level and the vaccine protective period could affect the estimation of the immunological surrogate for EV71 vaccine. A post-vaccination NTAb titer of 1:42 or more may be needed for long-term protection. NCT01508247.

  4. DNA Methylation and Gene Expression Profiling of Ewing Sarcoma Primary Tumors Reveal Genes That Are Potential Targets of Epigenetic Inactivation

    Directory of Open Access Journals (Sweden)

    Nikul Patel

    2012-01-01

    Full Text Available The role of aberrant DNA methylation in Ewing sarcoma is not completely understood. The methylation status of 503 genes in 52 formalin-fixed paraffin-embedded EWS tumors and 3 EWS cell lines was compared to human mesenchymal stem cell primary cultures (hMSCs using bead chip methylation analysis. Relative expression of methylated genes was assessed in 5-Aza-2-deoxycytidine-(5-AZA-treated EWS cell lines and in a cohort of primary EWS samples and hMSCs by gene expression and quantitative RT-PCR. 129 genes demonstrated statistically significant hypermethylation in EWS tumors compared to hMSCs. Thirty-six genes were profoundly methylated in EWS and unmethylated in hMSCs. 5-AZA treatment of EWS cell lines resulted in upregulation of expression of hundreds of genes including 162 that were increased by at least 2-fold. The expression of 19 of 36 candidate hypermethylated genes was increased following 5-AZA. Analysis of gene expression from an independent cohort of tumors confirmed decreased expression of six of nineteen hypermethylated genes (AXL, COL1A1, CYP1B1, LYN, SERPINE1, and VCAN. Comparing gene expression and DNA methylation analyses proved to be an effective way to identify genes epigenetically regulated in EWS. Further investigation is ongoing to elucidate the role of these epigenetic alterations in EWS pathogenesis.

  5. CFD analysis of the HYPER spallation target

    International Nuclear Information System (INIS)

    Cho, Chungho; Tak, Nam-il; Choi, Jae-Hyuk; Lee, Yong-Bum

    2008-01-01

    KAERI (Korea Atomic Energy Research Institute) is developing an accelerator driven system (ADS) named HYPER (HYbrid Power Extraction Reactor) for a transmutation of long-lived nuclear wastes. One of the challenging tasks for the HYPER system is to design a large spallation target with a beam power of 15-25 MW. The paper focuses on a thermal-hydraulic analysis of the active part of the HYPER target. Computational fluid dynamics (CFD) analysis was performed by using a commercial code CFX 5.7.1. Several advanced turbulence models with different grid structures were applied. The CFX results reveal a significant impact of the turbulence model on the window temperature. Particularly, the k-ε model predicts the lowest window temperature among the five investigated turbulence models

  6. Uncertainty Prediction in Passive Target Motion Analysis

    Science.gov (United States)

    2016-05-12

    Number 15/152,696 Filing Date 12 May 2016 Inventor John G. Baylog et al Address any questions concerning this matter to the Office of...300118 1 of 25 UNCERTAINTY PREDICTION IN PASSIVE TARGET MOTION ANALYSIS STATEMENT OF GOVERNMENT INTEREST [0001] The invention described herein...at an unknown location and following an unknown course relative to an observer 12. Observer 12 has a sensor array such as a passive sonar or radar

  7. Differential analysis of the inactivation of yeast cells induced by irradiation with various ionization densities

    International Nuclear Information System (INIS)

    Grundler, W.

    1979-03-01

    A quantitative investigation is presented on the radiation-induced inactivation of yeast cells in the first generations as a function of dose, repair, and various ionization densities. The study has been made to solve two main questions, i.e.: How do these cells reproduce, and how do they look like at the end of the investigation. Finding the answer to these questions, it was hoped, would lead to a description of survival in the colony test by defining the final fate of the cells which represent the stationary end state. The experiments were to clarify to what extent the dose-response curve yields only relatively general information on radiation-induced damage, or what kind of damage is mainly and best described. This supplementary information will help to improve the interpretation of many experiments having been made with this strain. (orig./MG) [de

  8. Molecular Composition Analysis of Distant Targets

    Science.gov (United States)

    Hughes, Gary B.; Lubin, Philip

    2017-01-01

    This document is the Final Report for NASA Innovative Advanced Concepts (NIAC) Phase I Grant 15-NIAC16A-0145, titled Molecular Composition Analysis of Distant Targets. The research was focused on developing a system concept for probing the molecular composition of cold solar system targets, such as Asteroids, Comets, Planets and Moons from a distant vantage, for example from a spacecraft that is orbiting the target (Hughes et al., 2015). The orbiting spacecraft is equipped with a high-power laser, which is run by electricity from photovoltaic panels. The laser is directed at a spot on the target. Materials on the surface of the target are heated by the laser beam, and begin to melt and then evaporate, forming a plume of asteroid molecules in front of the heated spot. The heated spot glows, producing blackbody illumination that is visible from the spacecraft, via a path through the evaporated plume. As the blackbody radiation from the heated spot passes through the plume of evaporated material, molecules in the plume absorb radiation in a manner that is specific to the rotational and vibrational characteristics of the specific molecules. A spectrometer aboard the spacecraft is used to observe absorption lines in the blackbody signal. The pattern of absorption can be used to estimate the molecular composition of materials in the plume, which originated on the target. Focusing on a single spot produces a borehole, and shallow subsurface profiling of the targets bulk composition is possible. At the beginning of the Phase I research, the estimated Technology Readiness Level (TRL) of the system was TRL-1. During the Phase I research, an end-to-end theoretical model of the sensor system was developed from first principles. The model includes laser energy and optical propagation, target heating, melting and evaporation of target material, plume density, thermal radiation from the heated spot, molecular cross section of likely asteroid materials, and estimation of the

  9. Analysis of directly driven ICF targets

    International Nuclear Information System (INIS)

    Velarde, G.; Aragones, J.M.; Gago, J.A.

    1986-01-01

    The current capabilities at DENIM for the analysis of directly driven targets are presented. These include theoretical, computational and applied physical studies and developments of detailed simulation models for the most relevant processes in ICF. The simulation of directly driven ICF targets is carried out with the one-dimensional NORCLA code developed at DENIM. This code contains two main segments: NORMA and CLARA, able to work fully coupled and in an iterative manner. NORMA solves the hydrodynamic equations in a lagrangian mesh. It has modular programs couple to it to treat the laser or particle beam interaction with matter. Equations of state, opacities and conductivities are taken from a DENIM atomic data library, generated externally with other codes that will also be explained in this work. CLARA solves the transport equation for neutrons, as well as for charged particles, and suprathermal electrons using discrete ordinates and finite element methods in the computational procedure. Parametric calculations of multilayered single-shell targets driven by heavy ion beams are also analyzed. Finally, conclusions are focused on the ongoing developments in the areas of interest such as: radiation transport, atomic physics, particle in cell method, charged particle transport, two-dimensional calculations and instabilities. (author)

  10. Failure probability analysis on mercury target vessel

    International Nuclear Information System (INIS)

    Ishikura, Syuichi; Futakawa, Masatoshi; Kogawa, Hiroyuki; Sato, Hiroshi; Haga, Katsuhiro; Ikeda, Yujiro

    2005-03-01

    Failure probability analysis was carried out to estimate the lifetime of the mercury target which will be installed into the JSNS (Japan spallation neutron source) in J-PARC (Japan Proton Accelerator Research Complex). The lifetime was estimated as taking loading condition and materials degradation into account. Considered loads imposed on the target vessel were the static stresses due to thermal expansion and static pre-pressure on He-gas and mercury and the dynamic stresses due to the thermally shocked pressure waves generated repeatedly at 25 Hz. Materials used in target vessel will be degraded by the fatigue, neutron and proton irradiation, mercury immersion and pitting damages, etc. The imposed stresses were evaluated through static and dynamic structural analyses. The material-degradations were deduced based on published experimental data. As a result, it was quantitatively confirmed that the failure probability for the lifetime expected in the design is very much lower, 10 -11 in the safety hull, meaning that it will be hardly failed during the design lifetime. On the other hand, the beam window of mercury vessel suffered with high-pressure waves exhibits the failure probability of 12%. It was concluded, therefore, that the leaked mercury from the failed area at the beam window is adequately kept in the space between the safety hull and the mercury vessel by using mercury-leakage sensors. (author)

  11. Nuclear Security: Target Analysis-rev

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Surinder Paul [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Gibbs, Philip W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bultz, Garl A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2014-03-01

    The objectives of this presentation are to understand target identification, including roll-up and protracted theft; evaluate target identification in the SNRI; recognize the target characteristics and consequence levels; and understand graded safeguards.

  12. Comparative analysis on inactivation kinetics of between piezotolerant and piezosensitive mutant strains of Saccharomyces cerevisiae under combinations of high hydrostatic pressure and temperature.

    Science.gov (United States)

    Nomura, Kazuki; Kuwabara, Yuki; Kuwabara, Wataru; Takahashi, Hiroyuki; Nakajima, Kanako; Hayashi, Mayumi; Iguchi, Akinori; Shigematsu, Toru

    2017-12-01

    We previously obtained a pressure-tolerant (piezotolerant) and a pressure sensitive (piezosensitive) mutant strain, under ambient temperature, from Saccharomyces cerevisiae strain KA31a. The inactivation kinetics of these mutants were analyzed at 150 to 250MPa with 4 to 40°C. By a multiple regression analysis, the pressure and temperature dependency of the inactivation rate constants k values of both mutants, as well as the parent strain KA31a, were well approximated with high correlation coefficients (0.92 to 0.95). For both mutants, as well as strain KA31a, the lowest k value was shown at a low pressure levels with around ambient temperature. The k value approximately increased with increase in pressure level, and with increase and decrease in temperature. The piezosensitive mutant strain a924E1 showed piezosensitivity at all pressure and temperature levels, compared with the parent strain KA31a. In contrast, the piezotolerant mutant strain a2568D8 showed piezotolerance at 4 to 20°C, but did not show significant piezotolerance at 40°C. These results of the variable influence of temperature on pressure inactivation of these strains would be important for better understanding of piezosensitive and piezotolerant mechanisms, as well as the pressure inactivation mechanism of S. cerevisiae. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Inactivation of Smad4 in gastric carcinomas.

    Science.gov (United States)

    Powell, S M; Harper, J C; Hamilton, S R; Robinson, C R; Cummings, O W

    1997-10-01

    Allelic loss of chromosome 18q has been noted in intestinal type gastric adenocarcinomas. Smad4 is a gene located at 18q that was recently cloned in humans and found to be significantly altered in pancreatic cancers. We sought to determine whether Smad4 genetic alterations played a significant role in gastric tumorigenesis by studying 35 gastric adenocarcinomas of all histopathological types and pathological stages. Microdissected specimens were used for mutational analysis of Smad4 at the nucleotide level, including the entire coding region and intron/exon boundaries. Allelic imbalance was also analyzed at the Smad4 locus using two nearby microsatellite markers. One case of apparent biallelic inactivation of Smad4 was found in our study of 35 gastric carcinomas. A nonsense point mutation at codon 334 was demonstrated, which, similar to other Smad4 mutations, is predicted to truncate the conserved COOH-terminal domain of this protein. This Smad4 C to T transition mutation was proven to be somatically acquired. Allelic loss was also noted on chromosome 18q at a marker near Smad4 in this mutated gastric cancer, apparently producing complete inactivation of Smad4 in this tumor. Significant 18q allelic loss (56% of 34 informative cases) was noted in our gastric carcinomas using microsatellite markers near the Smad4 locus, regardless of histological subtype or pathological stage. Additionally, three cases of microsatellite instability were observed. Thus, Smad4 inactivation was noted in our gastric carcinomas; however, this event was rare. The frequent loss of chromosomal arm 18q observed in gastric cancers suggests the presence of other tumor suppressor genes in this region that are involved in gastric tumorigenesis. Further studies are needed to identify these other targets of inactivation during gastric cancer development.

  14. Inactivation Data.xlsx

    Data.gov (United States)

    U.S. Environmental Protection Agency — The data set is a spreadsheet that contains results of inactivation experiments that were conducted to to determine the effectiveness of chlorine in inactivating B....

  15. Orbitofrontal cortex inactivation impairs between- but not within-session Pavlovian extinction: an associative analysis.

    Science.gov (United States)

    Panayi, Marios C; Killcross, Simon

    2014-02-01

    The orbitofrontal cortex (OFC) is argued to be the neural locus of Pavlovian outcome expectancies. Reinforcement learning theories argue that extinction learning in Pavlovian procedures is caused by the discrepancy between the expected value of the outcome (US) that is elicited by a predictive stimulus (CS), and the lack of experienced US. If the OFC represents Pavlovian outcome expectancies that are necessary for extinction learning, then disrupting OFC function prior to extinction training should impair extinction learning. This was tested. In experiment 1, Long Evans rats received infusions of saline or muscimol targeting the lateral OFC prior to three appetitive Pavlovian extinction sessions. Muscimol infused into the OFC disrupted between-session but not within-session extinction behaviour. This finding was not due to muscimol infusions disrupting the memory consolidation process per se as there was no effect of muscimol infusion when administered immediately post session (experiment 2). These findings support a role for the OFC in representing outcome expectancies that are necessary for learning. A number of ways in which disrupting outcome expectancy information might block learning will be discussed in the context of traditional associative learning theories and the associative structures they depend on. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Photodynamic Inactivation of Mammalian Viruses and Bacteriophages

    Directory of Open Access Journals (Sweden)

    Liliana Costa

    2012-06-01

    Full Text Available Photodynamic inactivation (PDI has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process.

  17. Neutron performance analysis for ESS target proposal

    International Nuclear Information System (INIS)

    Magán, M.; Terrón, S.; Thomsen, K.; Sordo, F.; Perlado, J.M.; Bermejo, F.J.

    2012-01-01

    In the course of discussing different target types for their suitability in the European Spallation Source (ESS) one main focus was on neutronics' performance. Diverse concepts have been assessed baselining some preliminary engineering and geometrical details and including some optimization. With the restrictions and resulting uncertainty imposed by the lack of detailed designs optimizations at the time of compiling this paper, the conclusion drawn is basically that there is a little difference in the neutronic yield of the investigated targets. Other criteria like safety, environmental compatibility, reliability and cost will thus dominate the choice of an ESS target.

  18. Molecular Composition Analysis of Distant Targets

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose a system capable of probing the molecular composition of cold solar system targets such as asteroids, comets, planets and moons from a distant vantage....

  19. Inactivation of Caliciviruses

    Directory of Open Access Journals (Sweden)

    Raymond Nims

    2013-03-01

    Full Text Available The Caliciviridae family of viruses contains clinically important human and animal pathogens, as well as vesivirus 2117, a known contaminant of biopharmaceutical manufacturing processes employing Chinese hamster cells. An extensive literature exists for inactivation of various animal caliciviruses, especially feline calicivirus and murine norovirus. The caliciviruses are susceptible to wet heat inactivation at temperatures in excess of 60 °C with contact times of 30 min or greater, to UV-C inactivation at fluence ≥30 mJ/cm2, to high pressure processing >200 MPa for >5 min at 4 °C, and to certain photodynamic inactivation approaches. The enteric caliciviruses (e.g.; noroviruses display resistance to inactivation by low pH, while the non-enteric species (e.g.; feline calicivirus are much more susceptible. The caliciviruses are inactivated by a variety of chemicals, including alcohols, oxidizing agents, aldehydes, and β-propiolactone. As with inactivation of viruses in general, inactivation of caliciviruses by the various approaches may be matrix-, temperature-, and/or contact time-dependent. The susceptibilities of the caliciviruses to the various physical and chemical inactivation approaches are generally similar to those displayed by other small, non-enveloped viruses, with the exception that the parvoviruses and circoviruses may require higher temperatures for inactivation, while these families appear to be more susceptible to UV-C inactivation than are the caliciviruses.

  20. Whole-genome transcriptional analysis of Escherichia coli during heat inactivation processes related to industrial cooking.

    Science.gov (United States)

    Guernec, A; Robichaud-Rincon, P; Saucier, L

    2013-08-01

    Escherichia coli K-12 was grown to the stationary phase, for maximum physiological resistance, in brain heart infusion (BHI) broth at 37°C. Cells were then heated at 58°C or 60°C to reach a process lethality value \\[\\mathbf{\\left(}{{\\mathit{F}}^{\\mathit{o}}}_{\\mathbf{70}}^{\\mathbf{10}}\\mathbf{\\right)} \\] of 2 or 3 or to a core temperature of 71°C (control industrial cooking temperature). Growth recovery and cell membrane integrity were evaluated immediately after heating, and a global transcription analysis was performed using gene expression microarrays. Only cells heated at 58°C with F(o) = 2 were still able to grow on liquid or solid BHI broth after heat treatment. However, their transcriptome did not differ from that of bacteria heated at 58°C with F(o) = 3 (P value for the false discovery rate [P-FDR] > 0.01), where no growth recovery was observed posttreatment. Genome-wide transcriptomic data obtained at 71°C were distinct from those of the other treatments without growth recovery. Quantification of heat shock gene expression by real-time PCR revealed that dnaK and groEL mRNA levels decreased significantly above 60°C to reach levels similar to those of control cells at 37°C (P citE, glyS, oppB, and asd, whose expression was upregulated at 71°C, may be worth investigating as good biomarkers for accurately determining the efficiency of heat treatments, especially when cells are too injured to be enumerated using growth media.

  1. Epitope mapping and biological function analysis of antibodies produced by immunization of mice with an inactivated Chinese isolate of severe acute respiratory syndrome-associated coronavirus (SARS-CoV)

    International Nuclear Information System (INIS)

    Chou, Te-hui W.; Wang, Shixia; Sakhatskyy, Pavlo V.; Mboudoudjeck, Innocent; Lawrence, John M.; Huang Song; Coley, Scott; Yang Baoan; Li Jiaming; Zhu Qingyu; Lu Shan

    2005-01-01

    Inactivated severe acute respiratory syndrome-associated coronavirus (SARS-CoV) has been tested as a candidate vaccine against the re-emergence of SARS. In order to understand the efficacy and safety of this approach, it is important to know the antibody specificities generated with inactivated SARS-CoV. In the current study, a panel of twelve monoclonal antibodies (mAbs) was established by immunizing Balb/c mice with the inactivated BJ01 strain of SARS-CoV isolated from the lung tissue of a SARS-infected Chinese patient. These mAbs could recognize SARS-CoV-infected cells by immunofluorescence analysis (IFA). Seven of them were mapped to the specific segments of recombinant spike (S) protein: six on S1 subunit (aa 12-798) and one on S2 subunit (aa 797-1192). High neutralizing titers against SARS-CoV were detected with two mAbs (1A5 and 2C5) targeting at a subdomain of S protein (aa 310-535), consistent with the previous report that this segment of S protein contains the major neutralizing domain. Some of these S-specific mAbs were able to recognize cleaved products of S protein in SARS-CoV-infected Vero E6 cells. None of the remaining five mAbs could recognize either of the recombinant S, N, M, or E antigens by ELISA. This study demonstrated that the inactivated SARS-CoV was able to preserve the immunogenicity of S protein including its major neutralizing domain. The relative ease with which these mAbs were generated against SARS-CoV virions further supports that subunit vaccination with S constructs may also be able to protect animals and perhaps humans. It is somewhat unexpected that no N-specific mAbs were identified albeit anti-N IgG was easily identified in SARS-CoV-infected patients. The availability of this panel of mAbs also provided potentially useful agents with applications in therapy, diagnosis, and basic research of SARS-CoV

  2. Pathogen inactivation techniques.

    Science.gov (United States)

    Pelletier, J P R; Transue, S; Snyder, E L

    2006-01-01

    The desire to rid the blood supply of pathogens of all types has led to the development of many technologies aimed at the same goal--eradication of the pathogen(s) without harming the blood cells or generating toxic chemical agents. This is a very ambitious goal, and one that has yet to be achieved. One approach is to shun the 'one size fits all' concept and to target pathogen-reduction agents at the Individual component types. This permits the development of technologies that might be compatible with, for example, plasma products but that would be cytocidal and thus incompatible with platelet concentrates or red blood cell units. The technologies to be discussed include solvent detergent and methylene blue treatments--designed to inactivate plasma components and derivatives; psoralens (S-59--amotosalen) designed to pathogen-reduce units of platelets; and two products aimed at red blood cells, S-303 (a Frale--frangible anchor-linker effector compound) and Inactine (a binary ethyleneimine). A final pathogen-reduction material that might actually allow one material to inactivate all three blood components--riboflavin (vitamin B2)--is also under development. The sites of action of the amotosalen (S-59), the S-303 Frale, Inactine, and riboflavin are all localized in the nucleic acid part of the pathogen. Solvent detergent materials act by dissolving the plasma envelope, thus compromising the integrity of the pathogen membrane and rendering it non-infectious. By disrupting the pathogen's ability to replicate or survive, its infectivity is removed. The degree to which bacteria and viruses are affected by a particular pathogen-reducing technology relates to its Gram-positive or Gram-negative status, to the sporulation characteristics for bacteria, and the presence of lipid or protein envelopes for viruses. Concerns related to photoproducts and other breakdown products of these technologies remain, and the toxicology of pathogen-reduction treatments is a major ongoing area

  3. Effects of inactivation of the anterior interpositus nucleus on the kinematic and dynamic control of multijoint movement.

    Science.gov (United States)

    Cooper, S E; Martin, J H; Ghez, C

    2000-10-01

    We previously showed that inactivating the anterior interpositus nucleus in cats disrupts prehension; paw paths, normally straight and accurate, become curved, hypometric, and more variable. In the present study, we determined the joint kinematic and dynamic origins of this impairment. Animals were restrained in a hammock and trained to reach and grasp a cube of meat from a narrow food well at varied heights; movements were monitored using the MacReflex analysis system. The anterior interpositus nucleus was inactivated by microinjection of the GABA agonist muscimol (0.25-0.5 microgram in 0.5 microliter saline). For each joint, we computed the torque due to gravity, inertial resistance (termed self torque), interjoint interactions (termed interaction torque), and the combined effects of active muscle contraction and passive soft tissue stretch (termed generalized muscle torque). Inactivation produced significant reductions in the amplitude, velocity, and acceleration of elbow flexion. However, these movements continued to scale normally with target height. Shoulder extension was reduced by inactivation but wrist angular displacement and velocity were not. Inactivation also produced changes in the temporal coordination between elbow, shoulder, and wrist kinematics. Dynamic analysis showed that elbow flexion both before and during inactivation was produced by the combined action of muscle and interaction torque, but that the timing depended on muscle torque. Elbow interaction and muscle torques were scaled to target height both before and during inactivation. Inactivation produced significant reductions in elbow flexor interaction and muscle torques. The duration of elbow flexor muscle torque was prolonged to compensate for the reduction in flexor interaction torque. Shoulder extension was produced by extensor interaction and muscle torques both before and during inactivation. Inactivation produced a reduction in shoulder extension, primarily by reduced interaction

  4. Identification, characterization and structure analysis of a type I ribosome-inactivating protein from Sapium sebiferum (Euphorbiaceae)

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Ying [Key Laboratory of Ion Beam Bioengineering and Bioenergy Forest Research Center of State Forestry Administration, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, Anhui (China); School of Life Sciences, University of Science and Technology of China, Hefei 230027, Anhui (China); College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471023, Henan (China); Mao, Yingji [Key Laboratory of Ion Beam Bioengineering and Bioenergy Forest Research Center of State Forestry Administration, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, Anhui (China); School of Life Sciences, University of Science and Technology of China, Hefei 230027, Anhui (China); Jin, Shan; Hou, Jinyan; Du, Hua [Key Laboratory of Ion Beam Bioengineering and Bioenergy Forest Research Center of State Forestry Administration, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, Anhui (China); Yang, Minglei, E-mail: yml888@mail.ustc.edu.cn [Key Laboratory of Ion Beam Bioengineering and Bioenergy Forest Research Center of State Forestry Administration, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, Anhui (China); Wu, Lifang, E-mail: lfwu@ipp.ac.cn [Key Laboratory of Ion Beam Bioengineering and Bioenergy Forest Research Center of State Forestry Administration, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, Anhui (China); School of Life Sciences, University of Science and Technology of China, Hefei 230027, Anhui (China)

    2015-08-07

    Ribosome-inactivating proteins (RIPs) are N-glycosidases (EC3.2.2.22) that universally inactivate the ribosome, thereby inhibiting protein biosynthesis. In this study, a novel type I RIPs named SEBIN was identified in Sapium sebiferum. Nuclear acid depurine experiment showed that SEBIN had rRNA N-Glycosidase activity. Further experiment indicated that SEBIN significantly inhibited Caenorhabditis elegans development as well as resulted in worm cell apoptosis. This is the first report to evaluate RIPs toxicity using C. elegans. We proposed that SEBIN may impaire C. elegans reproduction in a DNA-damage manner besides traditional protein synthesis inhibition approach. The predicted 3D structure was modeled using threading and ab initio modeling, and the r-RNA binding residue of SEBIN was identified through the protein-ligand docking approach. It showed the amino acid residues, Glu195, Asn81, Ala82, Tyr83, Glu164, Ser163, Ile159 and Arg167, played critical roles in catalytic process. Our results provided the theoretical foundation of structure–function relationships between enzymatic properties, toxicity and structural characterization of SEBIN. - Graphical abstract: Superposition of main chains of ricin (cyan) and SEBIN (brown), and adenine binding site residues of SEBIN. - Highlights: • A Ribosome-inactivating proteins gene (SEBIN) was isolated from Sapium sebiferum. • SEBIN had DNase activity besides widely reported ribosome inactivation via N-glycosidases activity. • SEBIN significantly inhibited Caenorhabditis elegans development in vivo. • SEBIN may impaire C. elegans reproduction in a DNA-damage manner with the aid of mutant strains hus-1 and clk-2. • The possible active sites between SEBIN and the adenine of rRNA were predicted.

  5. Identification, characterization and structure analysis of a type I ribosome-inactivating protein from Sapium sebiferum (Euphorbiaceae)

    International Nuclear Information System (INIS)

    Wu, Ying; Mao, Yingji; Jin, Shan; Hou, Jinyan; Du, Hua; Yang, Minglei; Wu, Lifang

    2015-01-01

    Ribosome-inactivating proteins (RIPs) are N-glycosidases (EC3.2.2.22) that universally inactivate the ribosome, thereby inhibiting protein biosynthesis. In this study, a novel type I RIPs named SEBIN was identified in Sapium sebiferum. Nuclear acid depurine experiment showed that SEBIN had rRNA N-Glycosidase activity. Further experiment indicated that SEBIN significantly inhibited Caenorhabditis elegans development as well as resulted in worm cell apoptosis. This is the first report to evaluate RIPs toxicity using C. elegans. We proposed that SEBIN may impaire C. elegans reproduction in a DNA-damage manner besides traditional protein synthesis inhibition approach. The predicted 3D structure was modeled using threading and ab initio modeling, and the r-RNA binding residue of SEBIN was identified through the protein-ligand docking approach. It showed the amino acid residues, Glu195, Asn81, Ala82, Tyr83, Glu164, Ser163, Ile159 and Arg167, played critical roles in catalytic process. Our results provided the theoretical foundation of structure–function relationships between enzymatic properties, toxicity and structural characterization of SEBIN. - Graphical abstract: Superposition of main chains of ricin (cyan) and SEBIN (brown), and adenine binding site residues of SEBIN. - Highlights: • A Ribosome-inactivating proteins gene (SEBIN) was isolated from Sapium sebiferum. • SEBIN had DNase activity besides widely reported ribosome inactivation via N-glycosidases activity. • SEBIN significantly inhibited Caenorhabditis elegans development in vivo. • SEBIN may impaire C. elegans reproduction in a DNA-damage manner with the aid of mutant strains hus-1 and clk-2. • The possible active sites between SEBIN and the adenine of rRNA were predicted

  6. Estimation by radiation inactivation of the size of functional units governing Sendai and influenza virus fusion

    International Nuclear Information System (INIS)

    Bundo-Morita, K.; Gibson, S.; Lenard, J.

    1987-01-01

    The target sizes associated with fusion and hemolysis carried out by Sendai virus envelope glycoproteins were determined by radiation inactivation analysis. The target size for influenza virus mediated fusion with erythrocyte ghosts at pH 5.0 was also determined for comparison. Sendai-mediated fusion with erythrocyte ghosts at pH 7.0 was likewise inactivated exponentially with increasing radiation dose, yielding a target size of 60 +/- 6 kDa, a value consistent with the molecular weight of a single F-protein molecule. The inactivation curve for Sendai-mediated fusion with cardiolipin liposomes at pH 7.0, however, was more complex. Assuming a multiple target-single hit model, the target consisted of 2-3 units of ca. 60 kDa each. A similar target was seen if the liposome contained 10% gangliosides or if the reaction was measured at pH 5.0, suggesting that fusion occurred by the same mechanism at high and low pH. A target size of 261 +/- 48 kDa was found for Sendai-induced hemolysis, in contrast with influenza, which had a more complex target size for this activity. Sendai virus fusion thus occurs by different mechanisms depending upon the nature of the target membrane, since it is mediated by different functional units. Hemolysis is mediated by a functional unit different from that associated with erythrocyte ghost fusion or with cardiolipin liposome fusion

  7. Targeted inactivation of integrin-linked kinase in hair follicle stem cells reveals an important modulatory role in skin repair after injury.

    Science.gov (United States)

    Nakrieko, Kerry-Ann; Rudkouskaya, Alena; Irvine, Timothy S; D'Souza, Sudhir J A; Dagnino, Lina

    2011-07-15

    Integrin-linked kinase (ILK) is key for normal epidermal morphogenesis, but little is known about its role in hair follicle stem cells and epidermal regeneration. Hair follicle stem cells are important contributors to newly formed epidermis following injury. We inactivated the Ilk gene in the keratin 15--expressing stem cell population of the mouse hair follicle bulge. Loss of ILK expression in these cells resulted in impaired cutaneous wound healing, with substantially decreased wound closure rates. ILK-deficient stem cells produced very few descendants that moved toward the epidermal surface and into the advancing epithelium that covers the wound. Furthermore, those few mutant cells that homed in the regenerated epidermis exhibited a reduced residence time. Paradoxically, ILK-deficient bulge stem cells responded to anagen growth signals and contributed to newly regenerated hair follicles during this phase of hair follicle growth. Thus ILK plays an important modulatory role in the normal contribution of hair follicle stem cell progeny to the regenerating epidermis following injury.

  8. Covalent Allosteric Inactivation of Protein Tyrosine Phosphatase 1B (PTP1B) by an Inhibitor-Electrophile Conjugate.

    Science.gov (United States)

    Punthasee, Puminan; Laciak, Adrian R; Cummings, Andrea H; Ruddraraju, Kasi Viswanatharaju; Lewis, Sarah M; Hillebrand, Roman; Singh, Harkewal; Tanner, John J; Gates, Kent S

    2017-04-11

    Protein tyrosine phosphatase 1B (PTP1B) is a validated drug target, but it has proven difficult to develop medicinally useful, reversible inhibitors of this enzyme. Here we explored covalent strategies for the inactivation of PTP1B using a conjugate composed of an active site-directed 5-aryl-1,2,5-thiadiazolidin-3-one 1,1-dioxide inhibitor connected via a short linker to an electrophilic α-bromoacetamide moiety. Inhibitor-electrophile conjugate 5a caused time-dependent loss of PTP1B activity consistent with a covalent inactivation mechanism. The inactivation occurred with a second-order rate constant of (1.7 ± 0.3) × 10 2 M -1 min -1 . Mass spectrometric analysis of the inactivated enzyme indicated that the primary site of modification was C121, a residue distant from the active site. Previous work provided evidence that covalent modification of the allosteric residue C121 can cause inactivation of PTP1B [Hansen, S. K., Cancilla, M. T., Shiau, T. P., Kung, J., Chen, T., and Erlanson, D. A. (2005) Biochemistry 44, 7704-7712]. Overall, our results are consistent with an unusual enzyme inactivation process in which noncovalent binding of the inhibitor-electrophile conjugate to the active site of PTP1B protects the nucleophilic catalytic C215 residue from covalent modification, thus allowing inactivation of the enzyme via selective modification of allosteric residue C121.

  9. Analysis of the dose-sparing effect of adjuvanted Sabin-inactivated poliovirus vaccine (sIPV).

    Science.gov (United States)

    Li, Zhuofan; Ding, Wenting; Guo, Qi; Liu, Ze; Zhu, Zhe; Song, Shaohui; Li, Weidong; Liao, Guoyang

    2018-03-30

    Sabin-based inactivated poliovirus vaccine(sIPV) is gradually replacing live-attenuated oral polio vaccine(OPV). Sabin-inactivated poliovirus vaccine(sIPV) has played a vital role in reducing economic burden of poliomyelitis and maintaining appropriate antibody levels in the population. However, due to its high cost and limited manufacturing capacity, sIPV cannot reach its full potential for global poliovirus eradication in developing countries. Therefore, to address this situation, we designed this study to evaluate the dose-sparing effects of AS03, CpG oligodeoxynucleotides (CpG-ODN) and polyinosinic:polycytidylic acid (PolyI:C) admixed with sIPV in rats. Our results showed that a combination of 1/4-dose sIPV adjuvanted with AS03 or AS03 with BW006 provides a seroconversion rate similar to that of full-dose sIPV without adjuvant and that, this rate is 5-fold higher than that of 1/4-dose sIPV without adjuvant after the first immunization. The combination of AS03 or AS03 with BW006 as an adjuvant effectively reduced sIPV dose by at least 4-fold and induced both humoral and cellular immune responses. Therefore, our study revealed that the combination of AS03 or AS03 with BW006 is a promising adjuvant for sIPV development.

  10. Preliminary analysis of a target factory for laser fusion

    International Nuclear Information System (INIS)

    Sherohman, J.W.; Hendricks, C.D.

    1980-01-01

    An analysis of a target factory leading to the determination of production expressions has provided for the basis of a parametric study. Parameters involving the input and output rate of a process system, processing yield factors, and multiple processing steps and production lines have been used to develop an understanding of their dependence on the rate of target injection for laser fusion. Preliminary results have indicated that a parametric study of this type will be important in the selection of processing methods to be used in the final production scheme of a target factory

  11. [Segment analysis of the target market of physiotherapeutic services].

    Science.gov (United States)

    Babaskin, D V

    2010-01-01

    The objective of the present study was to demonstrate the possibilities to analyse selected segments of the target market of physiotherapeutic services provided by medical and preventive-facilities of two major types. The main features of a target segment, such as provision of therapeutic massage, are illustrated in terms of two characteristics, namely attractiveness to the users and the ability of a given medical facility to satisfy their requirements. Based on the analysis of portfolio of the available target segments the most promising ones (winner segments) were selected for further marketing studies. This choice does not exclude the possibility of involvement of other segments of medical services in marketing activities.

  12. Analysis of target implosion irradiated by proton beam, (1)

    International Nuclear Information System (INIS)

    Tamba, Moritake; Nagata, Norimasa; Kawata, Shigeo; Niu, Keishiro.

    1982-10-01

    Numerical simulation and analysis were performed for the implosion of a hollow shell target driven by proton beam. The target consists of three layers of Pb, Al and DT. As the Al layer is heated by proton beam, the layer expands and pushes the DT layer toward the target center. To obtain the optimal velocity of DT implosion, the optimal target size and optimal layer thickness were determined. The target size is determined by, for example, the instability of the implosion or beam focusing on the target surface. The Rayleigh-Taylor instability and the unstable implosion due to the inhomogeneity were investigated. Dissipation, nonlinear effects and density gradient at the boundary were expected to reduce the growth rate of the Rayleigh-Taylor instability during the implosion. In order that the deviation of the boundary surface during the implosion is less than the thickness of fuel, the inhomogeneity of the temperature and the density of the target should be less than ten percent. The amplitude of the boundary surface roughness is required to be less than 4 micrometer. (Kato, T.)

  13. Introduction to charm decay analysis in fixed target experiments

    Energy Technology Data Exchange (ETDEWEB)

    Bediaga, Ignacio; Goebel, Carla

    1996-01-01

    We present an introduction to data analysis in Experimental High Energy Physics, and some concepts and useful tools are discussed. To illustrate, we use the data of E-791, a fixed target experiment recently realized at Fermilab. In particular, we analyse decay modes of D{sup +} meson with three charged particles in the final state. (author). 8 refs., 22 figs., 1 tab.

  14. Introduction to charm decay analysis in fixed target experiments

    International Nuclear Information System (INIS)

    Bediaga, Ignacio; Goebel, Carla.

    1996-01-01

    We present an introduction to data analysis in Experimental High Energy Physics, and some concepts and useful tools are discussed. To illustrate, we use the data of E-791, a fixed target experiment recently realized at Fermilab. In particular, we analyse decay modes of D + meson with three charged particles in the final state. (author). 8 refs., 22 figs., 1 tab

  15. Localized or Systemic {italic In Vivo} Heat-Inactivation of Human Immunodeficiency Virus (HIV): A Mathematical Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Pennypacker, Carl R.; Perelson, A.S.; Nys, N.; Nelson, G.; Sessler, D.I.

    1993-12-15

    Temperatures as low as 42 C, maintained for a little as 25 minutes, inactivate {approx}25% of HIV. Furthermore, human immunodeficiency virus (HIV)-infected T-cells are more sensitive to heat than healthy lymphocytes and susceptibility increases when the cells are pre-sensitized by exposure to tumor necrosis factor. Thus, induction of a whole-body hyperthermia, or hyperthermia specifically limited to tissues having a high viral load, are potential antiviral therapies for acquired immunodeficiency disease (AIDS). Accordingly, we incorporated therapeutic hyperthermia into an existing mathematical model which evaluates the interaction between HIV and CD4{sup +} T cells. Given the assumptions and limitations of this model, the results indicate that a daily therapy, reducing the population of actively infected cells by 40% or infectious virus by 50%, would effectively reverse the depletion of T cells. In contrast, a daily reduction of 20% of either actively infected cells or infectious virus would have a marginal effect. However, reduction by 20% of both actively infected cells and infectious virus could restore T cell numbers, assuming that permanent damage had not been inflicted on the thymus. Whole-body hyperthermia seems unlikely to be clinically useful, unless it can be induced non-invasively without general anesthesia. In contrast, heating directed specifically to areas of viral concentration may be effective and have a suitable risk/benefit ratio.

  16. Modeling of human factor Va inactivation by activated protein C

    Directory of Open Access Journals (Sweden)

    Bravo Maria

    2012-05-01

    Full Text Available Abstract Background Because understanding of the inventory, connectivity and dynamics of the components characterizing the process of coagulation is relatively mature, it has become an attractive target for physiochemical modeling. Such models can potentially improve the design of therapeutics. The prothrombinase complex (composed of the protease factor (FXa and its cofactor FVa plays a central role in this network as the main producer of thrombin, which catalyses both the activation of platelets and the conversion of fibrinogen to fibrin, the main substances of a clot. A key negative feedback loop that prevents clot propagation beyond the site of injury is the thrombin-dependent generation of activated protein C (APC, an enzyme that inactivates FVa, thus neutralizing the prothrombinase complex. APC inactivation of FVa is complex, involving the production of partially active intermediates and “protection” of FVa from APC by both FXa and prothrombin. An empirically validated mathematical model of this process would be useful in advancing the predictive capacity of comprehensive models of coagulation. Results A model of human APC inactivation of prothrombinase was constructed in a stepwise fashion by analyzing time courses of FVa inactivation in empirical reaction systems with increasing number of interacting components and generating corresponding model constructs of each reaction system. Reaction mechanisms, rate constants and equilibrium constants informing these model constructs were initially derived from various research groups reporting on APC inactivation of FVa in isolation, or in the presence of FXa or prothrombin. Model predictions were assessed against empirical data measuring the appearance and disappearance of multiple FVa degradation intermediates as well as prothrombinase activity changes, with plasma proteins derived from multiple preparations. Our work integrates previously published findings and through the cooperative

  17. A mathematical analysis of multiple-target SELEX.

    Science.gov (United States)

    Seo, Yeon-Jung; Chen, Shiliang; Nilsen-Hamilton, Marit; Levine, Howard A

    2010-10-01

    SELEX (Systematic Evolution of Ligands by Exponential Enrichment) is a procedure by which a mixture of nucleic acids can be fractionated with the goal of identifying those with specific biochemical activities. One combines the mixture with a specific target molecule and then separates the target-NA complex from the resulting reactions. The target-NA complex is separated from the unbound NA by mechanical means (such as by filtration), the NA is eluted from the complex, amplified by PCR (polymerase chain reaction), and the process repeated. After several rounds, one should be left with the nucleic acids that best bind to the target. The problem was first formulated mathematically in Irvine et al. (J. Mol. Biol. 222:739-761, 1991). In Levine and Nilsen-Hamilton (Comput. Biol. Chem. 31:11-25, 2007), a mathematical analysis of the process was given. In Vant-Hull et al. (J. Mol. Biol. 278:579-597, 1998), multiple target SELEX was considered. It was assumed that each target has a single nucleic acid binding site that permits occupation by no more than one nucleic acid. Here, we revisit Vant-Hull et al. (J. Mol. Biol. 278:579-597, 1998) using the same assumptions. The iteration scheme is shown to be convergent and a simplified algorithm is given. Our interest here is in the behavior of the multiple target SELEX process as a discrete "time" dynamical system. Our goal is to characterize the limiting states and their dependence on the initial distribution of nucleic acid and target fraction components. (In multiple target SELEX, we vary the target component fractions, but not their concentrations, as fixed and the initial pool of nucleic acids as a variable starting condition). Given N nucleic acids and a target consisting of M subtarget component species, there is an M × N matrix of affinities, the (i,j) entry corresponding to the affinity of the jth nucleic acid for the ith subtarget. We give a structure condition on this matrix that is equivalent to the following

  18. Ultraviolet inactivation of papain

    International Nuclear Information System (INIS)

    Baugher, J.F.; Grossweiner, L.I.

    1975-01-01

    Flash photolysis transient spectra (lambda > 250 nm) of aqueous papain showed that the initial products are the neutral tryptophan radical Trp (lambdasub(max) 510 nm), the tryptophan triplet state 3 Trp (lambdasub(max) 460 nm), the disulfide bridge electron adduct -SS - - (lambdasub(max) 420 nm) and the hydrated electron esub(aq) - . The -SS - - yield was not altered by nitrous oxide or air, indicating that the formation of this product does not involve electrons in the external medium. The original papain preparation was activated by irradiating under nitrogen. The action spectrum supports previous work attributing the low initial activity to blocking of cysteinyl site 25 with a mixed disulfide. Flask lamp irradiation in nitrogen led to activation at low starting activities and inactivation at higher starting activities, while only inactivation at the same quantum yield was observed with air saturation. The results are consistent with photoionization of an essential tryptophyl residue as the key inactivating step. (author)

  19. Computer-aided target tracking in motion analysis studies

    Science.gov (United States)

    Burdick, Dominic C.; Marcuse, M. L.; Mislan, J. D.

    1990-08-01

    Motion analysis studies require the precise tracking of reference objects in sequential scenes. In a typical situation, events of interest are captured at high frame rates using special cameras, and selected objects or targets are tracked on a frame by frame basis to provide necessary data for motion reconstruction. Tracking is usually done using manual methods which are slow and prone to error. A computer based image analysis system has been developed that performs tracking automatically. The objective of this work was to eliminate the bottleneck due to manual methods in high volume tracking applications such as the analysis of crash test films for the automotive industry. The system has proven to be successful in tracking standard fiducial targets and other objects in crash test scenes. Over 95 percent of target positions which could be located using manual methods can be tracked by the system, with a significant improvement in throughput over manual methods. Future work will focus on the tracking of clusters of targets and on tracking deformable objects such as airbags.

  20. Penetration analysis of projectile with inclined concrete target

    Directory of Open Access Journals (Sweden)

    Kim S.B.

    2015-01-01

    Full Text Available This paper presents numerical analysis result of projectile penetration with concrete target. We applied dynamic material properties of 4340 steels, aluminium and explosive for projectile body. Dynamic material properties were measured with static tensile testing machine and Hopkinson pressure bar tests. Moreover, we used three concrete damage models included in LS-DYNA 3D, such as SOIL_CONCRETE, CSCM (cap model with smooth interaction and CONCRETE_DAMAGE (K&C concrete models. Strain rate effect for concrete material is important to predict the fracture deformation and shape of concrete, and penetration depth for projectiles. CONCRETE_DAMAGE model with strain rate effect also applied to penetration analysis. Analysis result with CSCM model shows good agreement with penetration experimental data. The projectile trace and fracture shapes of concrete target were compared with experimental data.

  1. Penetration analysis of projectile with inclined concrete target

    Science.gov (United States)

    Kim, S. B.; Kim, H. W.; Yoo, Y. H.

    2015-09-01

    This paper presents numerical analysis result of projectile penetration with concrete target. We applied dynamic material properties of 4340 steels, aluminium and explosive for projectile body. Dynamic material properties were measured with static tensile testing machine and Hopkinson pressure bar tests. Moreover, we used three concrete damage models included in LS-DYNA 3D, such as SOIL_CONCRETE, CSCM (cap model with smooth interaction) and CONCRETE_DAMAGE (K&C concrete) models. Strain rate effect for concrete material is important to predict the fracture deformation and shape of concrete, and penetration depth for projectiles. CONCRETE_DAMAGE model with strain rate effect also applied to penetration analysis. Analysis result with CSCM model shows good agreement with penetration experimental data. The projectile trace and fracture shapes of concrete target were compared with experimental data.

  2. Molecular cloning and functional analysis of a recombinant ribosome-inactivating protein (alpha-momorcharin) from Momordica charantia.

    Science.gov (United States)

    Wang, Shuzhen; Zhang, Yubo; Liu, Honggao; He, Ying; Yan, Junjie; Wu, Zhihua; Ding, Yi

    2012-11-01

    Alpha-momorcharin (α-MC), a member of the ribosome-inactivating protein (RIP) family, has been used not only as antiviral, antimicrobial, and antitumor agents, but also as toxicant to protozoa, insects, and fungi. In this study, we expressed the protein in Escherichia coli Rosetta (DE3) pLysS strain and purified it by nickel-nitrilotriacetic acid affinity chromatography. A total of 85 mg of homogeneous protein was obtained from 1 l culture supernatant of Rosetta (DE3) pLysS, showing a high recovery rate of 73.9%. Protein activity assay indicated that α-MC had both N-glycosidase activity and DNA-nuclease activity, the former releasing RIP diagnostic RNA fragment (Endo's fragment) from rice rRNAs and the latter converting supercoiled circular DNA of plasmid pET-32a(+) into linear conformations in a concentration-dependent manner. Specially, we found that α-MC could inhibit the mycelial growth of Fusarium solani and Fusarium oxysporum with IC(50) values of 6.23 and 4.15 μM, respectively. Results of optical microscopy and transmission electron microscopy demonstrated that α-MC caused extensive septum formation, loss of integrity of the cell wall, separation of the cytoplasm from the cell wall, deformation of cells with irregular budding sites, and apoptosis in F. solani. Moreover, α-MC was active against Pseudomonas aeruginosa with an IC(50) value of 0.59 μM. The α-MC protein carries a high potential for the design of new antifungal drugs or the development of transgenic crops resistant to pathogens.

  3. Integrative analysis to select cancer candidate biomarkers to targeted validation

    Science.gov (United States)

    Heberle, Henry; Domingues, Romênia R.; Granato, Daniela C.; Yokoo, Sami; Canevarolo, Rafael R.; Winck, Flavia V.; Ribeiro, Ana Carolina P.; Brandão, Thaís Bianca; Filgueiras, Paulo R.; Cruz, Karen S. P.; Barbuto, José Alexandre; Poppi, Ronei J.; Minghim, Rosane; Telles, Guilherme P.; Fonseca, Felipe Paiva; Fox, Jay W.; Santos-Silva, Alan R.; Coletta, Ricardo D.; Sherman, Nicholas E.; Paes Leme, Adriana F.

    2015-01-01

    Targeted proteomics has flourished as the method of choice for prospecting for and validating potential candidate biomarkers in many diseases. However, challenges still remain due to the lack of standardized routines that can prioritize a limited number of proteins to be further validated in human samples. To help researchers identify candidate biomarkers that best characterize their samples under study, a well-designed integrative analysis pipeline, comprising MS-based discovery, feature selection methods, clustering techniques, bioinformatic analyses and targeted approaches was performed using discovery-based proteomic data from the secretomes of three classes of human cell lines (carcinoma, melanoma and non-cancerous). Three feature selection algorithms, namely, Beta-binomial, Nearest Shrunken Centroids (NSC), and Support Vector Machine-Recursive Features Elimination (SVM-RFE), indicated a panel of 137 candidate biomarkers for carcinoma and 271 for melanoma, which were differentially abundant between the tumor classes. We further tested the strength of the pipeline in selecting candidate biomarkers by immunoblotting, human tissue microarrays, label-free targeted MS and functional experiments. In conclusion, the proposed integrative analysis was able to pre-qualify and prioritize candidate biomarkers from discovery-based proteomics to targeted MS. PMID:26540631

  4. Single-Molecule Analysis for RISC Assembly and Target Cleavage.

    Science.gov (United States)

    Sasaki, Hiroshi M; Tadakuma, Hisashi; Tomari, Yukihide

    2018-01-01

    RNA-induced silencing complex (RISC) is a small RNA-protein complex that mediates silencing of complementary target RNAs. Biochemistry has been successfully used to characterize the molecular mechanism of RISC assembly and function for nearly two decades. However, further dissection of intermediate states during the reactions has been warranted to fill in the gaps in our understanding of RNA silencing mechanisms. Single-molecule analysis with total internal reflection fluorescence (TIRF) microscopy is a powerful imaging-based approach to interrogate complex formation and dynamics at the individual molecule level with high sensitivity. Combining this technique with our recently established in vitro reconstitution system of fly Ago2-RISC, we have developed a single-molecule observation system for RISC assembly. In this chapter, we summarize the detailed protocol for single-molecule analysis of chaperone-assisted assembly of fly Ago2-RISC as well as its target cleavage reaction.

  5. Bioinformatics analysis of Brucella vaccines and vaccine targets using VIOLIN.

    Science.gov (United States)

    He, Yongqun; Xiang, Zuoshuang

    2010-09-27

    Brucella spp. are Gram-negative, facultative intracellular bacteria that cause brucellosis, one of the commonest zoonotic diseases found worldwide in humans and a variety of animal species. While several animal vaccines are available, there is no effective and safe vaccine for prevention of brucellosis in humans. VIOLIN (http://www.violinet.org) is a web-based vaccine database and analysis system that curates, stores, and analyzes published data of commercialized vaccines, and vaccines in clinical trials or in research. VIOLIN contains information for 454 vaccines or vaccine candidates for 73 pathogens. VIOLIN also contains many bioinformatics tools for vaccine data analysis, data integration, and vaccine target prediction. To demonstrate the applicability of VIOLIN for vaccine research, VIOLIN was used for bioinformatics analysis of existing Brucella vaccines and prediction of new Brucella vaccine targets. VIOLIN contains many literature mining programs (e.g., Vaxmesh) that provide in-depth analysis of Brucella vaccine literature. As a result of manual literature curation, VIOLIN contains information for 38 Brucella vaccines or vaccine candidates, 14 protective Brucella antigens, and 68 host response studies to Brucella vaccines from 97 peer-reviewed articles. These Brucella vaccines are classified in the Vaccine Ontology (VO) system and used for different ontological applications. The web-based VIOLIN vaccine target prediction program Vaxign was used to predict new Brucella vaccine targets. Vaxign identified 14 outer membrane proteins that are conserved in six virulent strains from B. abortus, B. melitensis, and B. suis that are pathogenic in humans. Of the 14 membrane proteins, two proteins (Omp2b and Omp31-1) are not present in B. ovis, a Brucella species that is not pathogenic in humans. Brucella vaccine data stored in VIOLIN were compared and analyzed using the VIOLIN query system. Bioinformatics curation and ontological representation of Brucella vaccines

  6. Thermal Analysis of Fission Moly Target Solid Waste Storage

    Energy Technology Data Exchange (ETDEWEB)

    Son, Hyung Min; Park, Jonghark [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2016-10-15

    There are various ways to produce Mo-99. Among them, nuclear transmutation of uranium target became the major one owing to its superior specific activity. After the fission molybdenum (FM) target is irradiated, it is transported to treatment facility to extract wanted isotope. During the process, various forms of wastes are produced including filter cake and other solid wastes. The filter cake is mostly consisted of decaying uranium compounds. The solid wastes are then packaged and moved to storage facility which will stay there for considerable amount of time. Being the continuous source of heat, the solid wastes are required to be cooled for the certain amount of time before transported to the storage area. In this study, temperature evaluation of the storage facility is carried out with pre-cooling time sensitivity to check its thermal integrity. In this study, thermal analysis on the FM target solid waste storage is performed. Finite volume method is utilized to numerically discretize and solve the geometry of interest. Analysis shows that the developed method can simulate temperature behavior during storage process, but needs to be checked against other code to see calculation accuracy. Highest temperature distribution is observed when every hole is filled with waste containers. Sensitivity results on pre-cooling time shows that at least 13 months of cooling is necessary to keep the structure integrity.

  7. SPATIAL ANALYSIS TO SUPPORT GEOGRAPHIC TARGETING OF GENOTYPES TO ENVIRONMENTS

    Directory of Open Access Journals (Sweden)

    Glenn eHyman

    2013-03-01

    Full Text Available Crop improvement efforts have benefited greatly from advances in available data, computing technology and methods for targeting genotypes to environments. These advances support the analysis of genotype by environment interactions to understand how well a genotype adapts to environmental conditions. This paper reviews the use of spatial analysis to support crop improvement research aimed at matching genotypes to their most appropriate environmental niches. Better data sets are now available on soils, weather and climate, elevation, vegetation, crop distribution and local conditions where genotypes are tested in experimental trial sites. The improved data are now combined with spatial analysis methods to compare environmental conditions across sites, create agro-ecological region maps and assess environment change. Climate, elevation and vegetation data sets are now widely available, supporting analyses that were much more difficult even five or ten years ago. While detailed soil data for many parts of the world remains difficult to acquire for crop improvement studies, new advances in digital soil mapping are likely to improve our capacity. Site analysis and matching and regional targeting methods have advanced in parallel to data and technology improvements. All these developments have increased our capacity to link genotype to phenotype and point to a vast potential to improve crop adaptation efforts.

  8. Prediction methodologies for target scene generation in the aerothermal targets analysis program (ATAP)

    Science.gov (United States)

    Hudson, Douglas J.; Torres, Manuel; Dougherty, Catherine; Rajendran, Natesan; Thompson, Rhoe A.

    2003-09-01

    The Air Force Research Laboratory (AFRL) Aerothermal Targets Analysis Program (ATAP) is a user-friendly, engineering-level computational tool that features integrated aerodynamics, six-degree-of-freedom (6-DoF) trajectory/motion, convective and radiative heat transfer, and thermal/material response to provide an optimal blend of accuracy and speed for design and analysis applications. ATAP is sponsored by the Kinetic Kill Vehicle Hardware-in-the-Loop Simulator (KHILS) facility at Eglin AFB, where it is used with the CHAMP (Composite Hardbody and Missile Plume) technique for rapid infrared (IR) signature and imagery predictions. ATAP capabilities include an integrated 1-D conduction model for up to 5 in-depth material layers (with options for gaps/voids with radiative heat transfer), fin modeling, several surface ablation modeling options, a materials library with over 250 materials, options for user-defined materials, selectable/definable atmosphere and earth models, multiple trajectory options, and an array of aerodynamic prediction methods. All major code modeling features have been validated with ground-test data from wind tunnels, shock tubes, and ballistics ranges, and flight-test data for both U.S. and foreign strategic and theater systems. Numerous applications include the design and analysis of interceptors, booster and shroud configurations, window environments, tactical missiles, and reentry vehicles.

  9. Stakeholder analysis and mapping as targeted communication strategy.

    Science.gov (United States)

    Shirey, Maria R

    2012-09-01

    This department highlights change management strategies that may be successful in strategically planning and executing organizational change initiatives. With the goal of presenting practical approaches helpful to nurse leaders advancing organizational change, content includes evidence-based projects, tools, and resources that mobilize and sustain organizational change initiatives. In this article, the author highlights the importance of stakeholder theory and discusses how to apply the theory to conduct a stakeholder analysis. This article also provides an explanation of how to use related stakeholder mapping techniques with targeted communication strategies.

  10. Ideal MHD stability analysis of KSTAR target AT mode

    International Nuclear Information System (INIS)

    Yi, S.M.; Kim, J.H.; You, K.I.; Kim, J.Y.

    2009-01-01

    Full text: A main research objective of KSTAR (Korea Superconducting Tokamak Advanced Research) device is to demonstrate the steady-state operation capability of high-performance AT (Advanced Tokamak) mode. To meet this goal, it is critical for KSTAR to have a good MHD stability boundary, particularly against the high-beta ideal instabilities such as the external kink and the ballooning modes. To support this MHD stability KSTAR has been designed to have a strong plasma shape and a close interval between plasma and passive- plate wall. During the conceptual design phase of KSTAR, a preliminary study was performed to estimate the high beta MHD stability limit of KSTAR target AT mode using PEST and VACUUM codes and it was shown that the target AT mode can be stable up to β N ∼ 5 with a well-defined plasma pressure and current profiles. Recently, a new calculation has been performed to estimate the ideal stability limit in various KSTAR operating conditions using DCON code, and it has been observed that there is some difference between the new and old calculation results, particularly in the dependence of the maximum β N value on the toroidal mode number. Here, we thus present a more detailed analysis of the ideal MHD stability limit of KSTAR target AT mode using various codes, which include GATO as well as PEST and DCON, in the comparison of calculation results among the three codes. (author)

  11. Biochemical mechanism of action of a diketopiperazine inactivator of plasminogen activator inhibitor-1

    DEFF Research Database (Denmark)

    Einholm, Anja P; Pedersen, Katrine E; Wind, Troels

    2003-01-01

    -inactivated PAI-1 is inert to reaction with its target proteases and has a decreased susceptibility to non-target proteases, in spite of a generally increased proteolytic susceptibility of specific peptide bonds elsewhere in PAI-1. The properties of XR5118-inactivated PAI-1 were different from those of the so...

  12. Global analysis of small molecule binding to related protein targets.

    Directory of Open Access Journals (Sweden)

    Felix A Kruger

    2012-01-01

    Full Text Available We report on the integration of pharmacological data and homology information for a large scale analysis of small molecule binding to related targets. Differences in small molecule binding have been assessed for curated pairs of human to rat orthologs and also for recently diverged human paralogs. Our analysis shows that in general, small molecule binding is conserved for pairs of human to rat orthologs. Using statistical tests, we identified a small number of cases where small molecule binding is different between human and rat, some of which had previously been reported in the literature. Knowledge of species specific pharmacology can be advantageous for drug discovery, where rats are frequently used as a model system. For human paralogs, we demonstrate a global correlation between sequence identity and the binding of small molecules with equivalent affinity. Our findings provide an initial general model relating small molecule binding and sequence divergence, containing the foundations for a general model to anticipate and predict within-target-family selectivity.

  13. Protein targeting in the analysis of learning and memory: a potential alternative to gene targeting.

    Science.gov (United States)

    Gerlai, R; Williams, S P; Cairns, B; Van Bruggen, N; Moran, P; Shih, A; Caras, I; Sauer, H; Phillips, H S; Winslow, J W

    1998-11-01

    Gene targeting using homologous recombination in embryonic stem (ES) cells offers unprecedented precision with which one may manipulate single genes and investigate the in vivo effects of defined mutations in the mouse. Geneticists argue that this technique abrogates the lack of highly specific pharmacological tools in the study of brain function and behavior. However, by now it has become clear that gene targeting has some limitations too. One problem is spatial and temporal specificity of the generated mutation, which may appear in multiple brain regions or even in other organs and may also be present throughout development, giving rise to complex, secondary phenotypical alterations. This may be a disadvantage in the functional analysis of a number of genes associated with learning and memory processes. For example, several proteins, including neurotrophins--cell-adhesion molecules--and protein kinases, that play a significant developmental role have recently been suggested to be also involved in neural and behavioral plasticity. Knocking out genes of such proteins may lead to developmental alterations or even embryonic lethality in the mouse, making it difficult to study their function in neural plasticity, learning, and memory. Therefore, alternative strategies to gene targeting may be needed. Here, we suggest a potentially useful in vivo strategy based on systemic application of immunoadhesins, genetically engineered fusion proteins possessing the Fc portion of the human IgG molecule and, for example, a binding domain of a receptor of interest. These proteins are stable in vivo and exhibit high binding specificity and affinity for the endogenous ligand of the receptor, but lack the ability to signal. Thus, if delivered to the brain, immunoadhesins may specifically block signalling of the receptor of interest. Using osmotic minipumps, the protein can be infused in a localized region of the brain for a specified period of time (days or weeks). Thus, the location

  14. Mutual inactivation of Notch receptors and ligands facilitates developmental patterning.

    Directory of Open Access Journals (Sweden)

    David Sprinzak

    2011-06-01

    Full Text Available Developmental patterning requires juxtacrine signaling in order to tightly coordinate the fates of neighboring cells. Recent work has shown that Notch and Delta, the canonical metazoan juxtacrine signaling receptor and ligand, mutually inactivate each other in the same cell. This cis-interaction generates mutually exclusive sending and receiving states in individual cells. It generally remains unclear, however, how this mutual inactivation and the resulting switching behavior can impact developmental patterning circuits. Here we address this question using mathematical modeling in the context of two canonical pattern formation processes: boundary formation and lateral inhibition. For boundary formation, in a model motivated by Drosophila wing vein patterning, we find that mutual inactivation allows sharp boundary formation across a broader range of parameters than models lacking mutual inactivation. This model with mutual inactivation also exhibits robustness to correlated gene expression perturbations. For lateral inhibition, we find that mutual inactivation speeds up patterning dynamics, relieves the need for cooperative regulatory interactions, and expands the range of parameter values that permit pattern formation, compared to canonical models. Furthermore, mutual inactivation enables a simple lateral inhibition circuit architecture which requires only a single downstream regulatory step. Both model systems show how mutual inactivation can facilitate robust fine-grained patterning processes that would be difficult to implement without it, by encoding a difference-promoting feedback within the signaling system itself. Together, these results provide a framework for analysis of more complex Notch-dependent developmental systems.

  15. Challenges in thermal and hydraulic analysis of ADS target systems

    International Nuclear Information System (INIS)

    Groetzbach, G.; Batta, A.; Lefhalm, C.-H.; Otic, I.

    2004-01-01

    The liquid metal cooled spallation targets of Accelerator Driven nuclear reactor Systems obey high thermal loads; in addition some flow and cooling conditions are of a prototypical character; in contrast the operating conditions for the engaged materials are narrow; thus, the target development requires a very careful analysis by experimental and numerical means. Especially the cooling of the steel window, which is heated by the proton beam, needs special care. Some of the main goals of the experimental and numerical analyses of the thermal dynamics of those systems are discusses. The prediction of locally detached flows and of flows with larger recirculation areas suffers from insufficient turbulence modeling; this has to be compensated by using prototypical model experiments, e.g. with water, to select the adequate models and numerical schemes. The well known problems with the Reynolds analogy in predicting the heat transfer in liquid metals requires always prototypic liquid metal experiments to select and adapt the turbulent heat flux models. The uncertainties in liquid metal experiments cannot be neglected; so it is necessary to perform CFD calculations and experiments always hand in hand and to develop improve turbulent heat flux models. One contribution to an improved 3 or 4-equation model is deduced from recent Direct Numerical Simulation (DNS) data. (author)

  16. SeedVicious: Analysis of microRNA target and near-target sites.

    Science.gov (United States)

    Marco, Antonio

    2018-01-01

    Here I describe seedVicious, a versatile microRNA target site prediction software that can be easily fitted into annotation pipelines and run over custom datasets. SeedVicious finds microRNA canonical sites plus other, less efficient, target sites. Among other novel features, seedVicious can compute evolutionary gains/losses of target sites using maximum parsimony, and also detect near-target sites, which have one nucleotide different from a canonical site. Near-target sites are important to study population variation in microRNA regulation. Some analyses suggest that near-target sites may also be functional sites, although there is no conclusive evidence for that, and they may actually be target alleles segregating in a population. SeedVicious does not aim to outperform but to complement existing microRNA prediction tools. For instance, the precision of TargetScan is almost doubled (from 11% to ~20%) when we filter predictions by the distance between target sites using this program. Interestingly, two adjacent canonical target sites are more likely to be present in bona fide target transcripts than pairs of target sites at slightly longer distances. The software is written in Perl and runs on 64-bit Unix computers (Linux and MacOS X). Users with no computing experience can also run the program in a dedicated web-server by uploading custom data, or browse pre-computed predictions. SeedVicious and its associated web-server and database (SeedBank) are distributed under the GPL/GNU license.

  17. Phosphate analysis of natural sausage casings preserved in brines with phosphate additives as inactivating agent - Method validation.

    Science.gov (United States)

    Wijnker, J J; Tjeerdsma-van Bokhoven, J L M; Veldhuizen, E J A

    2009-01-01

    Certain phosphates have been identified as suitable additives for the improvement of the microbial and mechanical properties of processed natural sausage casings. When mixed with NaCl (sodium chloride) and used under specific treatment and storage conditions, these phosphates are found to prevent the spread of foot-and-mouth disease and classical swine fever via treated casings. The commercially available Quantichrom™ phosphate assay kit has been evaluated as to whether it can serve as a reliable and low-tech method for routine analysis of casings treated with phosphate. The outcome of this study indicates that this particular assay kit has sufficient sensitivity to qualitatively determine the presence of phosphate in treated casings without interference of naturally occurring phosphate in salt used for brines in which casings are preserved.

  18. In-depth resistome analysis by targeted metagenomics.

    Science.gov (United States)

    Lanza, Val F; Baquero, Fernando; Martínez, José Luís; Ramos-Ruíz, Ricardo; González-Zorn, Bruno; Andremont, Antoine; Sánchez-Valenzuela, Antonio; Ehrlich, Stanislav Dusko; Kennedy, Sean; Ruppé, Etienne; van Schaik, Willem; Willems, Rob J; de la Cruz, Fernando; Coque, Teresa M

    2018-01-15

    Antimicrobial resistance is a major global health challenge. Metagenomics allows analyzing the presence and dynamics of "resistomes" (the ensemble of genes encoding antimicrobial resistance in a given microbiome) in disparate microbial ecosystems. However, the low sensitivity and specificity of available metagenomic methods preclude the detection of minority populations (often present below their detection threshold) and/or the identification of allelic variants that differ in the resulting phenotype. Here, we describe a novel strategy that combines targeted metagenomics using last generation in-solution capture platforms, with novel bioinformatics tools to establish a standardized framework that allows both quantitative and qualitative analyses of resistomes. We developed ResCap, a targeted sequence capture platform based on SeqCapEZ (NimbleGene) technology, which includes probes for 8667 canonical resistance genes (7963 antibiotic resistance genes and 704 genes conferring resistance to metals or biocides), and 2517 relaxase genes (plasmid markers) and 78,600 genes homologous to the previous identified targets (47,806 for antibiotics and 30,794 for biocides or metals). Its performance was compared with metagenomic shotgun sequencing (MSS) for 17 fecal samples (9 humans, 8 swine). ResCap significantly improves MSS to detect "gene abundance" (from 2.0 to 83.2%) and "gene diversity" (26 versus 14.9 genes unequivocally detected per sample per million of reads; the number of reads unequivocally mapped increasing up to 300-fold by using ResCap), which were calculated using novel bioinformatic tools. ResCap also facilitated the analysis of novel genes potentially involved in the resistance to antibiotics, metals, biocides, or any combination thereof. ResCap, the first targeted sequence capture, specifically developed to analyze resistomes, greatly enhances the sensitivity and specificity of available metagenomic methods and offers the possibility to analyze genes

  19. Electron beam inactivation of Tulane virus on fresh produce, and mechanism of inactivation of human norovirus surrogates by electron beam irradiation.

    Science.gov (United States)

    Predmore, Ashley; Sanglay, Gabriel C; DiCaprio, Erin; Li, Jianrong; Uribe, R M; Lee, Ken

    2015-04-02

    Ionizing radiation, whether by electron beams or gamma rays, is a non-thermal processing technique used to improve the microbial safety and shelf-life of many different food products. This technology is highly effective against bacterial pathogens, but data on its effect against foodborne viruses is limited. A mechanism of viral inactivation has been proposed with gamma irradiation, but no published study discloses a mechanism for electron beam (e-beam). This study had three distinct goals: 1) evaluate the sensitivity of a human norovirus surrogate, Tulane virus (TV), to e-beam irradiation in foods, 2) compare the difference in sensitivity of TV and murine norovirus (MNV-1) to e-beam irradiation, and 3) determine the mechanism of inactivation of these two viruses by e-beam irradiation. TV was reduced from 7 log10 units to undetectable levels at target doses of 16 kGy or higher in two food matrices (strawberries and lettuce). MNV-1 was more resistant to e-beam treatment than TV. At target doses of 4 kGy, e-beam provided a 1.6 and 1.2 log reduction of MNV-1 in phosphate buffered saline (PBS) and Dulbecco's Modified Eagle Medium (DMEM), compared to a 1.5 and 1.8 log reduction of TV in PBS and Opti-MEM, respectively. Transmission electron microscopy revealed that increased e-beam doses negatively affected the structure of both viruses. Analysis of viral proteins by SDS-PAGE found that irradiation also degraded viral proteins. Using RT-PCR, irradiation was shown to degrade viral genomic RNA. This suggests that the mechanism of inactivation of e-beam was likely the same as gamma irradiation as the damage to viral constituents led to inactivation. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Integrative analysis of RUNX1 downstream pathways and target genes

    Directory of Open Access Journals (Sweden)

    Liu Marjorie

    2008-07-01

    Full Text Available Abstract Background The RUNX1 transcription factor gene is frequently mutated in sporadic myeloid and lymphoid leukemia through translocation, point mutation or amplification. It is also responsible for a familial platelet disorder with predisposition to acute myeloid leukemia (FPD-AML. The disruption of the largely unknown biological pathways controlled by RUNX1 is likely to be responsible for the development of leukemia. We have used multiple microarray platforms and bioinformatic techniques to help identify these biological pathways to aid in the understanding of why RUNX1 mutations lead to leukemia. Results Here we report genes regulated either directly or indirectly by RUNX1 based on the study of gene expression profiles generated from 3 different human and mouse platforms. The platforms used were global gene expression profiling of: 1 cell lines with RUNX1 mutations from FPD-AML patients, 2 over-expression of RUNX1 and CBFβ, and 3 Runx1 knockout mouse embryos using either cDNA or Affymetrix microarrays. We observe that our datasets (lists of differentially expressed genes significantly correlate with published microarray data from sporadic AML patients with mutations in either RUNX1 or its cofactor, CBFβ. A number of biological processes were identified among the differentially expressed genes and functional assays suggest that heterozygous RUNX1 point mutations in patients with FPD-AML impair cell proliferation, microtubule dynamics and possibly genetic stability. In addition, analysis of the regulatory regions of the differentially expressed genes has for the first time systematically identified numerous potential novel RUNX1 target genes. Conclusion This work is the first large-scale study attempting to identify the genetic networks regulated by RUNX1, a master regulator in the development of the hematopoietic system and leukemia. The biological pathways and target genes controlled by RUNX1 will have considerable importance in disease

  1. Free radical inactivation of trypsin

    International Nuclear Information System (INIS)

    Cudina, Ivana; Jovanovic, S.V.

    1988-01-01

    Reactivities of free radical oxidants, radical OH, Br2-anion radical and Cl 3 COO radical and a reductant, CO2-anion radical, with trypsin and reactive protein components were determined by pulse radiolysis of aqueous solutions at pH 7, 20 0 C. Highly reactive free radicals, radical OH, Br2-anion radical and CO2-anion radical, react with trypsin at diffusion controlled rates. Moderately reactive trichloroperoxy radical, k(Cl 3 COO radical + trypsin) preferentially oxidizes histidine residues. The efficiency of inactivation of trypsin by free radicals is inversely proportional to their reactivity. The yields of inactivation of trypsin by radical OH, Br2-anion radical and CO2-anion radical are low, G(inactivation) = 0.6-0.8, which corresponds to ∼ 10% of the initially produced radicals. In contrast, Cl 3 COO radical inactivates trypsin with ∼ 50% efficiency, i.e. G(inactivation) = 3.2. (author)

  2. Error Analysis of Fast Moving Target Geo-location in Wide Area Surveillance Ground Moving Target Indication Mode

    Directory of Open Access Journals (Sweden)

    Zheng Shi-chao

    2013-12-01

    Full Text Available As an important mode in airborne radar systems, Wide Area Surveillance Ground Moving Target Indication (WAS-GMTI mode has the ability of monitoring a large area in a short time, and then the detected moving targets can be located quickly. However, in real environment, many factors introduce considerable errors into the location of moving targets. In this paper, a fast location method based on the characteristics of the moving targets in WAS-GMTI mode is utilized. And in order to improve the location performance, those factors that introduce location errors are analyzed and moving targets are relocated. Finally, the analysis of those factors is proved to be reasonable by simulation and real data experiments.

  3. Inactivation of Microorganisms

    Science.gov (United States)

    Alzamora, Stella Maris; Guerrero, Sandra N.; Schenk, Marcela; Raffellini, Silvia; López-Malo, Aurelio

    Minimal processing techniques for food preservation allow better retention of product flavor, texture, color, and nutrient content than comparable conventional treatments. A wide range of novel alternative physical factors have been intensely investigated in the last two decades. These physical factors can cause inactivation of microorganisms at ambient or sublethal temperatures (e.g., high hydrostatic pressure, pulsed electric fields, ultrasound, pulsed light, and ultraviolet light). These technologies have been reported to reduce microorganism population in foods while avoiding the deleterious effects of severe heating on quality. Among technologies, high-energy ultrasound (i.e., intensities higher than 1 W/cm2, frequencies between 18 and 100 kHz) has attracted considerable interest for food preservation applications (Mason et al., 1996; Povey and Mason, 1998).

  4. Mean inactivation dose (D)

    International Nuclear Information System (INIS)

    Vijayakumar, S.; Ng, T.C.; Raudkivi, U.; Meaney, T.J.

    1990-01-01

    By predicting treatment outcome to radiotherapy from in vitro radiobiological parameters, not only individual patient treatments can be tailored, but also new promising treatment protocols can be tried in patients in whom unfavorable outcome is predicted. In this respect, choosing the right parameter can be very important. Unlike D 0 and N which provide information of the distal part of the survival curve, mean inactivation dose (D) estimates overall radiosensitivity. However, the parameters reflecting the response at the clinically relevant low-dose region are neglected in the literature. In a literature survey of 98 papers in which survival curves or D 0 /N were used, only in 2 D was used. In 21 papers the D 0 /n values were important in drawing conclusions. By calculating D in 3 of these 21 papers, we show that the conclusion drawn may be altered with the use of D. The importance of ''low-dose-region-parameters'' is reviewed. (orig.)

  5. Qweak Data Analysis for Target Modeling Using Computational Fluid Dynamics

    Science.gov (United States)

    Moore, Michael; Covrig, Silviu

    2015-04-01

    The 2.5 kW liquid hydrogen (LH2) target used in the Qweak parity violation experiment is the highest power LH2 target in the world and the first to be designed with Computational Fluid Dynamics (CFD) at Jefferson Lab. The Qweak experiment determined the weak charge of the proton by measuring the parity-violating elastic scattering asymmetry of longitudinally polarized electrons from unpolarized liquid hydrogen at small momentum transfer (Q2 = 0 . 025 GeV2). This target met the design goals of bench-marked with the Qweak target data. This work is an essential ingredient in future designs of very high power low noise targets like MOLLER (5 kW, target noise asymmetry contribution < 25 ppm) and MESA (4.5 kW).

  6. Radiological error: analysis, standard setting, targeted instruction and teamworking

    International Nuclear Information System (INIS)

    FitzGerald, Richard

    2005-01-01

    Diagnostic radiology does not have objective benchmarks for acceptable levels of missed diagnoses [1]. Until now, data collection of radiological discrepancies has been very time consuming. The culture within the specialty did not encourage it. However, public concern about patient safety is increasing. There have been recent innovations in compiling radiological interpretive discrepancy rates which may facilitate radiological standard setting. However standard setting alone will not optimise radiologists' performance or patient safety. We must use these new techniques in radiological discrepancy detection to stimulate greater knowledge sharing, targeted instruction and teamworking among radiologists. Not all radiological discrepancies are errors. Radiological discrepancy programmes must not be abused as an instrument for discrediting individual radiologists. Discrepancy rates must not be distorted as a weapon in turf battles. Radiological errors may be due to many causes and are often multifactorial. A systems approach to radiological error is required. Meaningful analysis of radiological discrepancies and errors is challenging. Valid standard setting will take time. Meanwhile, we need to develop top-up training, mentoring and rehabilitation programmes. (orig.)

  7. Transmutation technology development; thermal hydraulic power analysis and structure analysis of the HYPER target beam window

    Energy Technology Data Exchange (ETDEWEB)

    Choi, J. H.; Ju, E. S.; Song, M. K.; Jeon, Y. Z. [Gyeongsang National University, Jinju (Korea)

    2002-03-01

    A thermal hydraulic power analysis, a structure analysis and optimization computation for some design factor for the design of spallation target suitable for HYPER with 1000 MW thermal power in this study was performed. Heat generation formula was used which was evaluated recently based on the LAHET code, mainly to find the maximum beam current under given computation conditions. Thermal hydraulic power of HYPER target system was calculated using FLUENT code, structure conducted by inputting the data into ANSYS. On the temp of beam windows and the pressure distribution calculated using FLUENT. Data transformation program was composed apply the data calculated using FLUENT being commercial CFD code and ANSYS being FEM code for CFX structure analysis. A basic study was conducted on various singular target to obtain fundamental data on the shape for optimum target design. A thermal hydraulic power analysis and structure analysis were conducted on the shapes of parabolic, uniform, scanning beams to choose the optimum shape of beam current analysis was done according to some turbulent model to simulate the real flow. To evaluate the reliability of numerical analysis result, benchmarking of FLUENT code reformed at SNU and Korea Advanced Institute of Science and Technology and it was compared to CFX in the possession of Korea Atomic Energy Research Institute and evaluated. Reliable deviation was observed in the results calculated using FLUENT code, but temperature deviation of about 200 .deg. C was observed in the result from CFX analysis at optimum design condition. Several benchmarking were performed on the basis of numerical analysis concerning conventional HYPER. It was possible to allow a beam arrests of 17.3 mA in the case of the {phi} 350 mm parabolic beam suggested to the optimum in nuclear transmutation when stress equivalent to VON-MISES was calculated to be 140 MPa. 29 refs., 109 figs. (Author)

  8. CRISPRTarget: bioinformatic prediction and analysis of crRNA targets

    NARCIS (Netherlands)

    Biswas, A.; Gagnon, J.N.; Brouns, S.J.J.; Fineran, P.C.; Brown, C.M.

    2013-01-01

    The bacterial and archaeal CRISPR/Cas adaptive immune system targets specific protospacer nucleotide sequences in invading organisms. This requires base pairing between processed CRISPR RNA and the target protospacer. For type I and II CRISPR/Cas systems, protospacer adjacent motifs (PAM) are

  9. Size determination of an equilibrium enzymic system by radiation inactivation

    International Nuclear Information System (INIS)

    Simon, P.; Swillens, S.; Dumont, J.E.

    1982-01-01

    Radiation inactivation of complex enzymic systems is currently used to determine the enzyme size and the molecular organization of the components in the system. An equilibrium model was simulated describing the regulation of enzyme activity by association of the enzyme with a regulatory unit. It is assumed that, after irradiation, the system equilibrates before the enzyme activity is assayed. The theoretical results show that the target-size analysis of these numerical data leads to a bad estimate of the enzyme size. Moreover, some implicit assumptions such as the transfer of radiation energy between non-covalently bound molecules should be verified before interpretation of target-size analysis. It is demonstrated that the apparent target size depends on the parameters of the system, namely the size and the concentration of the components, the equilibrium constant, the relative activities of free enzyme and enzymic complex, the existence of energy transfer, and the distribution of the components between free and bound forms during the irradiation. (author)

  10. Targeting gender: A content analysis of alcohol advertising in magazines.

    Science.gov (United States)

    Jung, A-Reum; Hovland, Roxanne

    2016-01-01

    Creating target specific advertising is fundamental to maximizing advertising effectiveness. When crafting an advertisement, message and creative strategies are considered important because they affect target audiences' attitudes toward advertised products. This study endeavored to find advertising strategies that are likely to have special appeal for men or women by examining alcohol advertising in magazines. The results show that the substance of the messages is the same for men and women, but they only differ in terms of presentation. However, regardless of gender group, the most commonly used strategies in alcohol advertising are appeals to the target audience's emotions.

  11. Monetary targeting and financial system characteristics : An empirical analysis

    NARCIS (Netherlands)

    Samarina, A..

    2012-01-01

    This paper investigates how reforms and characteristics of the financial system affect the likelihood of countries to abandon their strategy of monetary targeting. Apart from financial system characteristics, we include macroeconomic, fiscal, and institutional factors potentially associated with

  12. The Terahertz Scattering Analysis of Rough Metallic and Dielectric Targets

    Directory of Open Access Journals (Sweden)

    Mou Yuan

    2018-02-01

    Full Text Available The terahertz scattering characteristics of metallic and dielectric rough targets is important for the investigation of the terahertz radar targets properties. According to the stationary phase theory and scalar approximation, if the radius of curvature at any point of the surface is much larger than the incident wavelength, and the wavelength is also much longer than the surface height function and Root-Mean-Square (RMS surface slope, the coherent and incoherent scattering Radar Cross Section (RCS of rough metallic and dielectric targets can be obtained. Based on the stationary phase approximation, the coherent RCS of rough conductors, smooth dielectric targets and rough dielectric targets can be easily deputed. The scattering characteristics of electrically large smooth Al and painted spheres are investigated in this paper, and the calculated RCS are verified by Mie scattering theory, the error is less than 0.1 dBm2. Based on lambert theory, it is demonstrated that the incoherent RCS is analyzed with better precision if the rough surfaces are divided into much more facets. In this paper, the coherent and incoherent scattering of rough Al and painted spheres are numerically observed, and the effects of surface roughness and materials are analyzed. The conclusions provide theoretical foundation for the terahertz scattering characteristics of electrically large rough targets.

  13. Genome-wide analysis of Polycomb targets in Drosophila

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, Yuri B.; Kahn, Tatyana G.; Nix, David A.; Li,Xiao-Yong; Bourgon, Richard; Biggin, Mark; Pirrotta, Vincenzo

    2006-04-01

    Polycomb Group (PcG) complexes are multiprotein assemblages that bind to chromatin and establish chromatin states leading to epigenetic silencing. PcG proteins regulate homeotic genes in flies and vertebrates but little is known about other PcG targets and the role of the PcG in development, differentiation and disease. We have determined the distribution of the PcG proteins PC, E(Z) and PSC and of histone H3K27 trimethylation in the Drosophila genome. At more than 200 PcG target genes, binding sites for the three PcG proteins colocalize to presumptive Polycomb Response Elements (PREs). In contrast, H3 me3K27 forms broad domains including the entire transcription unit and regulatory regions. PcG targets are highly enriched in genes encoding transcription factors but receptors, signaling proteins, morphogens and regulators representing all major developmental pathways are also included.

  14. Targets for bulk hydrogen analysis using thermal neutrons

    CERN Document Server

    Csikai, J; Buczko, C M

    2002-01-01

    The reflection property of substances can be characterized by the reflection cross-section of thermal neutrons, sigma subbeta. A combination of the targets with thin polyethylene foils allowed an estimation of the flux depression of thermal neutrons caused by a bulk sample containing highly absorbing elements or compounds. Some new and more accurate sigma subbeta values were determined by using the combined target arrangement. For the ratio, R of the reflection and the elastic scattering cross-sections of thermal neutrons, R=sigma subbeta/sigma sub E sub L a value of 0.60+-0.02 was found on the basis of the data obtained for a number of elements from H to Pb. Using this correlation factor, and the sigma sub E sub L values, the unknown sigma subbeta data can be deduced. The equivalent thicknesses, to polyethylene or hydrogen, of the different target materials were determined from the sigma subbeta values.

  15. Docking analysis targeted to the whole enzyme: an application to the prediction of inhibition of PTP1B by thiomorpholine and thiazolyl derivatives.

    Science.gov (United States)

    Ganou, C A; Eleftheriou, P Th; Theodosis-Nobelos, P; Fesatidou, M; Geronikaki, A A; Lialiaris, T; Rekka, E A

    2018-02-01

    PTP1b is a protein tyrosine phosphatase involved in the inactivation of insulin receptor. Since inhibition of PTP1b may prolong the action of the receptor, PTP1b has become a drug target for the treatment of type II diabetes. In the present study, prediction of inhibition using docking analysis targeted specifically to the active or allosteric site was performed on 87 compounds structurally belonging to 10 different groups. Two groups, consisting of 15 thiomorpholine and 10 thiazolyl derivatives exhibiting the best prediction results, were selected for in vitro evaluation. All thiomorpholines showed inhibitory action (with IC 50 = 4-45 μΜ, Ki = 2-23 μM), while only three thiazolyl derivatives showed low inhibition (best IC 50 = 18 μΜ, Ki = 9 μΜ). However, free binding energy (E) was in accordance with the IC 50 values only for some compounds. Docking analysis targeted to the whole enzyme revealed that the compounds exhibiting IC 50 values higher than expected could bind to other peripheral sites with lower free energy, E o , than when bound to the active/allosteric site. A prediction factor, E- (Σ Eo × 0.16), which takes into account lower energy binding to peripheral sites, was proposed and was found to correlate well with the IC 50 values following an asymmetrical sigmoidal equation with r 2 = 0.9692.

  16. Functional size of vacuolar H+ pumps: Estimates from radiation inactivation studies

    International Nuclear Information System (INIS)

    Sarafian, V.; Poole, R.J.

    1991-01-01

    The PPase and the ATPase from red beet (Beta vulgaris) vacuolar membranes were subjected to radiation inactivation by a 60 Co source in both the native tonoplast and detergent-solubilized states, in order to determine their target molecular sizes. Analysis of the residual phosphohydrolytic and proton transport activities, after exposure to varying doses of radiation, yielded exponential relationships between the activities and radiation doses. The deduced target molecular sizes for PPase activity in native and solubilized membranes were 125kD and 259kD respectively and 327kD for H + -transport. This suggests that the minimum number of subunits of 67kD for PPi hydrolysis is two in the native state and four after Triton X-100 solubilization. At least four subunits would be required for H + -translocation. Analysis of the ATPase inactivation patterns revealed target sizes of 384kD and 495kD for ATP hydrolysis in native and solubilized tonoplast respectively and 430kD for H + -transport. These results suggest that the minimum size for hydrolytic or transport functions is relatively constant for the ATPase

  17. Radiation inactivation of T7 phage

    International Nuclear Information System (INIS)

    Becker, D.; Redpath, J.L.; Grossweiner, L.I.

    1978-01-01

    The radiation inactivation of T7 phage by 25-MeV electron pulses has been measured in various media containing a wide concentration range of radical scavenging solutes and in the presence of protective and sensitizing agents. The dependence of sensitivity on pulse dose, from 1 mrad to 3.6 krad, is attributed to radical depletion via bimolecular processes. The survival data are analyzed by extending target theory to include diffusive reactions of primary and secondary radicals generated in the medium. It is concluded that OH radicals are the principal primary inactivating species and that secondary radicals from Br - , CNS - , uracil, glucose, ribose, sucrose, tyrosine, and histidine are lethal to some extent. In nutrient broth or 100 mM histidine, psoralen derivatives, Actinomycin D, and Mitomycin C are anoxic sensitizers. It is proposed that the psoralens promote the formation of non-strand break lesions as the sensitization mechanism. The target theory based on diffusional kinetics is applicable to other systems including single cells

  18. Inflation targeting and inflation performance : a comparative analysis

    NARCIS (Netherlands)

    Samarina, Anna; De Haan, Jakob; Terpstra, M.

    2014-01-01

    This article examines how the impact of inflation targeting on inflation performance depends on the choice of country samples, adoption dates, time periods and methodological approaches. We apply two different estimation methods - difference-in-differences and propensity score matching - for our

  19. Analysis of Myc-induced histone modifications on target chromatin.

    Directory of Open Access Journals (Sweden)

    Francesca Martinato

    Full Text Available The c-myc proto-oncogene is induced by mitogens and is a central regulator of cell growth and differentiation. The c-myc product, Myc, is a transcription factor that binds a multitude of genomic sites, estimated to be over 10-15% of all promoter regions. Target promoters generally pre-exist in an active or poised chromatin state that is further modified by Myc, contributing to fine transcriptional regulation (activation or repression of the afferent gene. Among other mechanisms, Myc recruits histone acetyl-transferases to target chromatin and locally promotes hyper-acetylation of multiple lysines on histones H3 and H4, although the identity and combination of the modified lysines is unknown. Whether Myc dynamically regulates other histone modifications (or marks at its binding sites also remains to be addressed. Here, we used quantitative chromatin immunoprecipitation (qChIP to profile a total of 24 lysine-acetylation and -methylation marks modulated by Myc at target promoters in a human B-cell line with a regulatable c-myc transgene. Myc binding promoted acetylation of multiple lysines, primarily of H3K9, H3K14, H3K18, H4K5 and H4K12, but significantly also of H4K8, H4K91 and H2AK5. Dimethylation of H3K79 was also selectively induced at target promoters. A majority of target promoters showed co-induction of multiple marks - in various combinations - correlating with recruitment of the two HATs tested (Tip60 and HBO1, incorporation of the histone variant H2A.Z and transcriptional activation. Based on this and previous findings, we surmise that Myc recruits the Tip60/p400 complex to achieve a coordinated histone acetylation/exchange reaction at activated promoters. Our data are also consistent with the additive and redundant role of multiple acetylation events in transcriptional activation.

  20. Thermal shock analysis of liquid-mercury spallation target

    CERN Document Server

    Ishikura, S; Futakawa, M; Hino, R; Date, H

    2002-01-01

    The developments of the neutron scattering facilities are carried out under the high-intensity proton accelerator project promoted by JAERI and KEK. To estimate the structural integrity of the heavy liquid-metal (Hg) target used as a spallation neutron source in a MW-class neutron scattering facility, dynamic stress behavior due to the incident of a 1 MW-pulsed proton beam was analyzed by using FEM code. Two-type target containers with semi-cylindrical type and flat-plate type window were used as models for analyses. As a result, it is confirmed that the stress (pressure wave) generated by dynamic thermal shock becomes the largest at the center of window, and the flat-plate type window is more advantageous from the structural viewpoint than the semi-cylindrical type window. It has been understood that the stress generated in the window by the pressure wave can be treated as the secondary stress. (author)

  1. Analysis of an XADS Target with the System Code TRACE

    International Nuclear Information System (INIS)

    Jaeger, Wadim; Sanchez Espinoza, Victor H.; Feng, Bo

    2008-01-01

    Accelerator-driven systems (ADS) present an option to reduce the radioactive waste of the nuclear industry. The experimental Accelerator-Driven System (XADS) has been designed to investigate the feasibility of using ADS on an industrial scale to burn minor actinides. The target section lies in the middle of the subcritical core and is bombarded by a proton beam to produce spallation neutrons. The thermal energy produced from this reaction requires a heat removal system for the target section. The target is cooled by liquid lead-bismuth-eutectics (LBE) in the primary system which in turn transfers the heat via a heat exchanger (HX) to the secondary coolant, Diphyl THT (DTHT), a synthetic diathermic fluid. Since this design is still in development, a detailed investigation of the system is necessary to evaluate the behavior during normal and transient operations. Due to the lack of experimental facilities and data for ADS, the analyses are mostly done using thermal hydraulic codes. In addition to evaluating the thermal hydraulics of the XADS, this paper also benchmarks a new code developed by the NRC, TRACE, against other established codes. The events used in this study are beam power switch-on/off transients and a loss of heat sink accident. The obtained results from TRACE were in good agreement with the results of various other codes. (authors)

  2. Analysis of Mo99 production irradiating 20% U targets

    International Nuclear Information System (INIS)

    Calabrese, C. Ruben; Grant, Carlos R.; Marajofsky, Andres; Parkansky, David G.

    1999-01-01

    At present time, the National Atomic Energy Commission is producing about 800 Ci of Mo99 per week irradiating 90% enriched uranium-aluminum alloy plate targets in the RA-3 reactor, a 5 MW. Mtr type one. In order to change to 20% enriched uranium, and to increase the production to about 3000 Ci per week some configurations were studied with rod and plate geometry with uranium (20% enriched) -aluminum targets. The first case was the irradiation of a plate target element in the normal reactor configuration. Results showed a good efficiency, but both reactivity value and power density were too high. An element with rods was also analyzed, but results showed a poor efficiency, too much aluminum involved in the process, although a low reactivity and an acceptable rod power density. Finally, a solution consisting of plate elements with a Zircaloy cladding was adopted, which has shown not only a good efficiency, but it is also acceptable from the viewpoint of safety, heat transference criteria and feasibility

  3. Functional significance of the oligomeric structure of the Na,K-pump from radiation inactivation and ligand binding

    International Nuclear Information System (INIS)

    Norby, J.G.; Jensen, J.

    1991-01-01

    The present article is concerned with the oligomeric structure and function of the Na,K-pump (Na,K-ATPase). The questions we have addressed, using radiation inactivation and target size analysis as well as ligand binding, are whether the minimal structural unit and the functional unit have more than one molecule of the catalytic subunit, alpha. The authors first discuss the fundamentals of the radiation inactivation method and emphasize the necessity for rigorous internal standardization with enzymes of known molecular mass. They then demonstrate that the radiation inactivation of Na,K-ATPase is a stepwise process which leads to intermediary fragments of the alpha-subunit with partial catalytic activity. From the target size analysis it is most likely that the membrane-bound Na,K-ATPase is structurally organized as a diprotomer containing two alpha-subunits. Determination of ADP- and ouabain-binding site stoichiometry favors a theory with one substrate site per (alpha beta) 2. 47 references

  4. Proteomics analysis of antimalarial targets of Garcinia mangostana Linn.

    Institute of Scientific and Technical Information of China (English)

    Wanna; Chaijaroenkul; Artitiya; Thiengsusuk; Kanchana; Rungsihirunrat; Stephen; Andrew; Ward; Kesara; Na-Bangchang

    2014-01-01

    Objective:To investigate possible protein targets for antimalarial activity of Garcina mangostana Linn.(G.mangostana)(pericarp)in 3D7 Plasmodium falciparum clone using 2-dimensional electrophoresis and liquid chromatography mass-spectrometry(LC/MS/MS).Methods:3D7 Plasmodium falciparum was exposed to the crude ethanolic extract of G.mangostana Linn.(pericarp)at the concentrations of 12μg/mL(1C50level:concentration that inhibits parasite growth by 50%)and 30μg/mL(1C90level:concentration that inhibits parasite growth by 90%)for 12 h.Parasite proteins were separated by 2-dimensional electrophoresis and identified by LC/MS/MS.Results:At the IC50concentration,about 82%of the expressed parasite proteins were matched with the control(non-exposed),while at the IC90concentration,only 15%matched proteins were found.The selected protein spots from parasite exposed to the plant extract at the concentration of 12μg/mL were identified as eneymes that play role in glycolysis pathway,i.e.,phosphoglyeerate mutase putative,L-lactate dehydrogenase/glyceraldehyde-3-phosphate dehydrogenase,and fruetose-bisphosphate aldolase/phosphoglyeerate kinase.The proteosome was found in parasite exposed to 30μg/mL of the extract.Conclusions:Results suggest that proteins involved in the glycolysis pathway may be the targets for antimalarial activity of G.mangostana Linn.(pericarp).

  5. Thermal analysis of titanium drive-in target for D-D neutron generation.

    Science.gov (United States)

    Jung, N S; Kim, I J; Kim, S J; Choi, H D

    2010-01-01

    Thermal analysis was performed for a titanium drive-in target of a D-D neutron generator. Computational fluid dynamics code CFX-5 was used in this study. To define the heat flux term for the thermal analysis, beam current profile was measured. Temperature of the target was calculated at some of the operating conditions. The cooling performance of the target was evaluated by means of the comparison of the calculated maximum target temperature and the critical temperature of titanium. Copyright 2009 Elsevier Ltd. All rights reserved.

  6. Influvac, a trivalent inactivated subunit influenza vaccine.

    Science.gov (United States)

    Zuccotti, Gian Vincenzo; Fabiano, Valentina

    2011-01-01

    Influenza represents a major sanitary and socio-economic burden and vaccination is universally considered the most effective strategy for preventing the disease and its complications. Traditional influenza vaccines have been on the market since the late 1940s, with million of doses administered annually worldwide, and demonstrated a substantial efficacy and safety. The trivalent inactivated subunit vaccine has been available for more than 25 years and has been studied in healthy children, adults and the elderly and in people affected by underlying chronic medical conditions. We describe vaccine technology focusing on subunit vaccine production procedures and mode of action and provide updated information on efficacy and safety available data. A review of efficacy and safety data in healthy subjects and in high risk populations from major sponsor- and investigator-driven studies. The vaccine showed a good immunogenicity and a favorable safety profile in all target groups. In the panorama of actually available influenza vaccines, trivalent inactivated subunit vaccine represents a well-established tool for preventing flu and the associated complications.

  7. A Genotypic Analysis of Five P. aeruginosa Strains after Biofilm Infection by Phages Targeting Different Cell Surface Receptors

    Directory of Open Access Journals (Sweden)

    Diana P. Pires

    2017-06-01

    Full Text Available Antibiotic resistance constitutes one of the most serious threats to the global public health and urgently requires new and effective solutions. Bacteriophages are bacterial viruses increasingly recognized as being good alternatives to traditional antibiotic therapies. In this study, the efficacy of phages, targeting different cell receptors, against Pseudomonas aeruginosa PAO1 biofilm and planktonic cell cultures was evaluated over the course of 48 h. Although significant reductions in the number of viable cells were achieved for both cases, the high level of adaptability of the bacteria in response to the selective pressure caused by phage treatment resulted in the emergence of phage-resistant variants. To further investigate the genetic makeup of phage-resistant variants isolated from biofilm infection experiments, some of these bacteria were selected for phenotypic and genotypic characterization. Whole genome sequencing was performed on five phage-resistant variants and all of them carried mutations affecting the galU gene as well as one of pil genes. The sequencing analysis further revealed that three of the P. aeruginosa PAO1 variants carry large deletions (>200 kbp in their genomes. Complementation of the galU mutants with wild-type galU in trans restored LPS expression on the bacterial cell surface of these bacterial strains and rendered the complemented strains to be sensitive to phages. This provides unequivocal evidence that inactivation of galU function was associated with resistance to the phages that uses LPS as primary receptors. Overall, this work demonstrates that P. aeruginosa biofilms can survive phage attack and develop phage-resistant variants exhibiting defective LPS production and loss of type IV pili that are well adapted to the biofilm mode of growth.

  8. Kinetic analysis of the effects of target structure on siRNA efficiency

    Science.gov (United States)

    Chen, Jiawen; Zhang, Wenbing

    2012-12-01

    RNAi efficiency for target cleavage and protein expression is related to the target structure. Considering the RNA-induced silencing complex (RISC) as a multiple turnover enzyme, we investigated the effect of target mRNA structure on siRNA efficiency with kinetic analysis. The 4-step model was used to study the target cleavage kinetic process: hybridization nucleation at an accessible target site, RISC-mRNA hybrid elongation along with mRNA target structure melting, target cleavage, and enzyme reactivation. At this model, the terms accounting for the target accessibility, stability, and the seed and the nucleation site effects are all included. The results are in good agreement with that of experiments which show different arguments about the structure effects on siRNA efficiency. It shows that the siRNA efficiency is influenced by the integrated factors of target's accessibility, stability, and the seed effects. To study the off-target effects, a simple model of one siRNA binding to two mRNA targets was designed. By using this model, the possibility for diminishing the off-target effects by the concentration of siRNA was discussed.

  9. Bioinformatic analysis to discover putative drug targets against ...

    African Journals Online (AJOL)

    /

    2012-01-26

    Jan 26, 2012 ... JVIRTUAL GEL. GELBANK was available from the NCBI FTP server. This website incorporates only completed genomes and information pertinent to 2-DE. Link is available at www.gelbank.anl.gov. JVirGel is a software for the simulation and analysis of proteomics data (http://www.jvirgel.de/). The Java TM.

  10. Bim nuclear translocation and inactivation by viral interferon regulatory factor.

    Directory of Open Access Journals (Sweden)

    Young Bong Choi

    2010-08-01

    Full Text Available Viral replication efficiency is in large part governed by the ability of viruses to counteract pro-apoptotic signals induced by infection of the host cell. Human herpesvirus 8 (HHV-8 uses several strategies to block the host's innate antiviral defenses via interference with interferon and apoptotic signaling. Contributors include the four viral interferon regulatory factors (vIRFs 1-4, which function in dominant negative fashion to block cellular IRF activities in addition to targeting IRF signaling-induced proteins such as p53 and inhibiting other inducers of apoptosis such as TGFbeta receptor-activated Smad transcription factors. Here we identify direct targeting by vIRF-1 of BH3-only pro-apoptotic Bcl-2 family member Bim, a key negative regulator of HHV-8 replication, to effect its inactivation via nuclear translocation. vIRF-1-mediated relocalization of Bim was identified in transfected cells, by both immunofluorescence assay and western analysis of fractionated cell extracts. Also, co-localization of vIRF-1 and Bim was detected in nuclei of lytically infected endothelial cells. In vitro co-precipitation assays using purified vIRF-1 and Bim revealed direct interaction between the proteins, and Bim-binding residues of vIRF-1 were mapped by deletion and point mutagenesis. Generation and experimental utilization of Bim-refractory vIRF-1 variants revealed the importance of vIRF-1:Bim interaction, specifically, in pro-replication and anti-apoptotic activity of vIRF-1. Furthermore, blocking of the interaction with cell-permeable peptide corresponding to the Bim-binding region of vIRF-1 confirmed the relevance of vIRF-1:Bim association to vIRF-1 pro-replication activity. To our knowledge, this is the first report of an IRF protein that interacts with a Bcl-2 family member and of nuclear sequestration of Bim or any other member of the family as a means of inactivation. The data presented reveal a novel mechanism utilized by a virus to control

  11. Integrative Analysis of CRISPR/Cas9 Target Sites in the Human HBB Gene

    Directory of Open Access Journals (Sweden)

    Yumei Luo

    2015-01-01

    Full Text Available Recently, the clustered regularly interspaced short palindromic repeats (CRISPR system has emerged as a powerful customizable artificial nuclease to facilitate precise genetic correction for tissue regeneration and isogenic disease modeling. However, previous studies reported substantial off-target activities of CRISPR system in human cells, and the enormous putative off-target sites are labor-intensive to be validated experimentally, thus motivating bioinformatics methods for rational design of CRISPR system and prediction of its potential off-target effects. Here, we describe an integrative analytical process to identify specific CRISPR target sites in the human β-globin gene (HBB and predict their off-target effects. Our method includes off-target analysis in both coding and noncoding regions, which was neglected by previous studies. It was found that the CRISPR target sites in the introns have fewer off-target sites in the coding regions than those in the exons. Remarkably, target sites containing certain transcriptional factor motif have enriched binding sites of relevant transcriptional factor in their off-target sets. We also found that the intron sites have fewer SNPs, which leads to less variation of CRISPR efficiency in different individuals during clinical applications. Our studies provide a standard analytical procedure to select specific CRISPR targets for genetic correction.

  12. Cost Minimization Analysis of Hypnotic Drug: Target Controlled Inhalation Anesthesia (TCIA Sevoflurane and Target Controlled Infusion (TCI Propofol

    Directory of Open Access Journals (Sweden)

    Made Wiryana

    2016-09-01

    Full Text Available Background: Cost minimization analysis is a pharmaco-economic study used to compare two or more health interventions that have been shown to have the same effect, similar or equivalent. With limited health insurance budget from the Indonesian National Social Security System implementation in 2015, the quality control and the drug cost are two important things that need to be focused. The application of pharmaco-economic study results in the selection and use of drugs more effectively and efficiently. Objective: To determine cost minimization analysis of hypnotic drug between a target controlled inhalation anesthesia (TCIA sevoflurane and a target controlled infusion (TCI propofol in patients underwent a major oncologic surgery in Sanglah General Hospital. Methods: Sixty ASA physical status I-II patients underwent major oncologic surgery were divided into two groups. Group A was using TCIA sevoflurane and group B using TCI propofol. Bispectral index monitor (BIS index was used to evaluate the depth of anesthesia. The statistical tests used are the Shapiro-Wilk test, Lavene test, Mann-Whitney U test and unpaired t-test (α = 0.05. The data analysis used the Statistical Package for Social Sciences (SPSS for Windows. Results: In this study, the rate of drug used per unit time in group A was 0.12 ml sevoflurane per minute (± 0.03 and the group B was 7.25 mg propofol per minute (±0.98. Total cost of hypnotic drug in group A was IDR598.43 (IQR 112.47 per minute, in group B was IDR703.27 (IQR 156.73 per minute (p>0.05. Conclusions: There was no statistically significant difference from the analysis of the drug cost minimization hypnotic drug in a major oncologic surgery using TCIA sevoflurane and TCI propofol.

  13. Integrative genomic and functional analysis of human oral squamous cell carcinoma cell lines reveals synergistic effects of FAT1 and CASP8 inactivation.

    Science.gov (United States)

    Hayes, Tyler F; Benaich, Nathan; Goldie, Stephen J; Sipilä, Kalle; Ames-Draycott, Ashley; Cai, Wenjun; Yin, Guangliang; Watt, Fiona M

    2016-12-01

    Oral squamous cell carcinoma (OSCC) is genetically highly heterogeneous, which contributes to the challenges of treatment. To create an in vitro model that accurately reflects this heterogeneity, we generated a panel of HPV-negative OSCC cell lines. By whole exome sequencing of the lines and matched patient blood samples, we demonstrate that the mutational spectrum of the lines is representative of primary OSCC in The Cancer Genome Atlas. We show that loss of function mutations in FAT1 (an atypical cadherin) and CASP8 (Caspase 8) frequently occur in the same tumour. OSCC cells with inactivating FAT1 mutations exhibited reduced intercellular adhesion. Knockdown of FAT1 and CASP8 individually or in combination in OSCC cells led to increased cell migration and clonal growth, resistance to Staurosporine-induced apoptosis and, in some cases, increased terminal differentiation. The OSCC lines thus represent a valuable resource for elucidating the impact of different mutations on tumour behaviour. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  14. Structure of suicide-inactivated β-hydroxydecanoyl-thioester dehydrase

    International Nuclear Information System (INIS)

    Schwab, J.M.; Ho, C.K.; Li, W.B.; Townsend, C.A.; Salituro, G.M.

    1986-01-01

    β-Hydroxydecanoylthioester dehydrase, the key enzyme in biosynthesis of unsaturated fatty acids under anaerobic conditions, equilibrates thioesters of (R)-3-hydroxydecanoic acid, E-2-decenoic acid, and Z-3-decenoic acid. Dehydrase is irreversibly inactivated by the N-acetylcysteamine thioester of 3-decynoic acid (3-decynoyl-NAC), via dehydrase-catalyzed isomerization to 2,3-decadienoyl-NAC. To probe the relationship between normal catalysis and suicide inactivation, the structure of the inactivated enzyme has been studied. 3-[2- 13 C]Decynoyl-NAC was synthesized and incubated with dehydrase. 13 C NMR showed that attack of 2,3-decadienoyl-NAC by the active site histidine gives 3-histidinyl-3-decenoyl-NAC, which slowly rearranges to the more stable Δ 2 isomer. Model histidine-allene adducts have been made and characterized. Analysis of NMR data show that the C=C configuration of the decenoyl moiety of enzyme-bound inactivator is E. The suggestion that the mechanism of dehydrase inactivation parallels its normal mechanism of action is supported these findings

  15. Pulsed dielectric barrier discharge for Bacillus subtilis inactivation in water

    Science.gov (United States)

    Hernández-Arias, A. N.; Rodríguez-Méndez, B. G.; López-Callejas, R.; Valencia-Alvarado, R.; Mercado-Cabrera, A.; Peña-Eguiluz, R.; Barocio, S. R.; Muñoz-Castro, A. E.; de la Piedad Beneitez, A.

    2012-06-01

    The inactivation of Bacillus subtilis bacteria in water has been experimentally studied by means of a pulsed dielectric barrier discharge (PDBD) in a coaxial reactor endowed with an alumina dielectric. The plasma source is capable of operating at atmospheric pressure with gas, water or hybrid gas-liquid media at adjustable 25 kV pulses, 30 μs long and at a 500 Hz frequency. In order to evaluate the inactivation efficiency of the system, a set of experiments were designed on the basis of oxygen flow control. The initial data have showed a significant bacterial rate reduction of 103-107 CFU/mL. Additional results proved that applying an oxygen flow for a few seconds during the PDBD treatment inactivates the Bacillus subtilis population with 99.99% effectiveness. As a reference, without gas flow but with the same exposure times, this percentage is reduced to ~90%. The analysis of the relationship between inactivation rate and chemical species in the discharge has been carried out using optical emission spectroscopy as to identifying the main reactive species. Reactive oxygen species such as atomic oxygen and ozone tuned out to be the dominant germicidal species. Some proposed inactivation mechanisms of this technique are discussed.

  16. Pulsed dielectric barrier discharge for Bacillus subtilis inactivation in water

    International Nuclear Information System (INIS)

    Hernández-Arias, A N; López-Callejas, R; De la Piedad Beneitez, A; Rodríguez-Méndez, B G; Valencia-Alvarado, R; Mercado-Cabrera, A; Peña-Eguiluz, R; Barocio, S R; Muñoz-Castro, A E

    2012-01-01

    The inactivation of Bacillus subtilis bacteria in water has been experimentally studied by means of a pulsed dielectric barrier discharge (PDBD) in a coaxial reactor endowed with an alumina dielectric. The plasma source is capable of operating at atmospheric pressure with gas, water or hybrid gas-liquid media at adjustable 25 kV pulses, 30 μs long and at a 500 Hz frequency. In order to evaluate the inactivation efficiency of the system, a set of experiments were designed on the basis of oxygen flow control. The initial data have showed a significant bacterial rate reduction of 10 3 -10 7 CFU/mL. Additional results proved that applying an oxygen flow for a few seconds during the PDBD treatment inactivates the Bacillus subtilis population with 99.99% effectiveness. As a reference, without gas flow but with the same exposure times, this percentage is reduced to ∼90%. The analysis of the relationship between inactivation rate and chemical species in the discharge has been carried out using optical emission spectroscopy as to identifying the main reactive species. Reactive oxygen species such as atomic oxygen and ozone tuned out to be the dominant germicidal species. Some proposed inactivation mechanisms of this technique are discussed.

  17. Coupling analysis of the target temperature and thermal stress due to pulsed ion beam

    International Nuclear Information System (INIS)

    Yan Jie; Liu Meng; Lin Jufang; An Li; Long Xinggui

    2013-01-01

    Background: Target temperature has an important effect on the target life for the sealed neutron generator without cooling system. Purpose: To carry out the thermal-mechanical coupling analysis of the film-substrate target bombarded by the pulsed ion beam. Methods: The indirect coupling Finite Element Method (FEM) with a 2-dimensional time-space Gaussian axisymmetric power density as heat source was used to simulate the target temperature and thermal stress fields. Results: The effects of the target temperature and thermal stress fields under difference pulse widths and beam sizes were analyzed in terms of the FEM results. Conclusions: Combining with the temperature requirement and the thermal stress inducing film thermal mechanical destruction effect of the sealed neutron generator film-substrate targets, an optimized pulsed ion beam work status was proposed. (authors)

  18. Beyond typing and grading: target analysis in individualized therapy as a new challenge for tumour pathology.

    Science.gov (United States)

    Kreipe, Hans H; von Wasielewski, Reinhard

    2007-01-01

    In order to bring about its beneficial effects in oncology, targeted therapy depends on accurate target analysis. Whether cells of a tumour will be sensitive to a specific treatment is predicted by the detection of appropriate targets in cancer tissue by immunohistochemistry or molecular methods. In most instances this is performed by histopathologists. Reliability and reproducibility of tissue-based target analysis in histopathology require novel measures of quality assurance by internal and external controls. As a model for external quality assurance in targeted therapy an annual inter-laboratory trial has been set up in Germany applying tissue arrays with up to 60 mammary cancer samples which are tested by participants for expression of HER2/neu and steroid hormone receptors.

  19. Thermal hydraulics analysis of LIBRA-SP target chamber

    International Nuclear Information System (INIS)

    Mogahed, E.A.

    1996-01-01

    LIBRA-SP is a conceptual design study of an inertially confined 1000 MWe fusion power reactor utilizing self-pinched light ion beams. There are 24 ion beams which are arranged around the reactor cavity. The reaction chamber is an upright cylinder with an inverted conical roof resembling a mushroom, and a pool floor. The vertical sides of the cylinder are occupied by a blanket zone consisting of many perforated rigid HT-9 ferritic steel tubes called PERITs (PEr-forated RIgid Tube). The breeding/cooling material, liquid lead-lithium, flows through the PERITs, providing protection to the reflector/vacuum chamber so as to make it a lifetime component. The neutronics analysis and cavity hydrodynamics calculations are performed to account for the neutron heating and also to determine the effects of vaporization/condensation processes on the surface heat flux. The steady state nuclear heating distribution at the midplane is used for thermal hydraulics calculations. The maximum surface temperature of the HT-9 is chosen to not exceed 625 degree C to avoid drastic deterioration of the metal's mechanical properties. This choice restricts the thermal hydraulics performance of the reaction cavity. The inlet first surface coolant bulk temperature is 370 degree C, and the heat exchanger inlet coolant bulk temperature is 502 degree C. 4 refs., 6 figs., 2 tabs

  20. Analysis of drug adversiting targeted to health professionals

    Directory of Open Access Journals (Sweden)

    Marcela Campos Esqueff Abdalla

    2017-08-01

    Full Text Available The advertising of medicines is the dissemination of the product by the pharmaceutical industry, with emphasis on brand, aiming to promote their prescription and/or purchase. This practice must comply with the legal provisions in effect determined by Brazilian National Surveillance Agency. The present work aimed to analyze advertisements of medicines offered by the industry to health professionals. The capture of advertisements covered physician offices of various specialties, public and private hospitals and magazines directed at health professionals. The analysis of the collected parts involved the verification of legibility and viewing of information required, as well as the compliance with the health legislation that regulates the promotion and advertising of medicines in Brazil – agency’s resolution n. 96/2008. The results showed that no piece meets the health legislation in full. Most industries employs strategies that hinder access to restricted information of use of the medicine, as contra-indications, for example, constituting an obstacle to rational use. It was also observed the presence of indications other than those approved by the agency and use indication for different age groups in the specified product registration. It is obvious the need for a new model controller and more rigid regulator that prioritize above all particular interests, a major importance, that is the society. This must be protected from false advertising and abusive, promoting the rational use of medicines.

  1. Nucleus incertus inactivation impairs spatial learning and memory in rats.

    Science.gov (United States)

    Nategh, Mohsen; Nikseresht, Sara; Khodagholi, Fariba; Motamedi, Fereshteh

    2015-02-01

    Nucleus incertus (NI) is a pontine nucleus which releases mainly GABA and relaxin-3 in rats. Its suggested functions include response to stress, arousal, and modulation of hippocampal theta rhythm. Since the role of NI in learning and memory has not been well characterized, therefore the involvement of this nucleus in spatial learning and memory and the aftermath hippocampal levels of c-fos and pCREB were evaluated. NI was targeted by implanting cannula in male rats. For reference memory, NI was inactivated by lidocaine (0.4 μl, 4%) at three stages of acquisition, consolidation and retrieval in Morris water maze paradigm. For working memory, NI was inactivated in acquisition and retrieval phases. Injection of lidocaine prior to the first training session of reference memory significantly increased the distance moved, suggesting that inactivation of NI delays acquisition in this spatial task. Inactivation also interfered with the retrieval phase of spatial reference memory, as the time in target quadrant for lidocaine group was less, and the escape latency was higher compared to the control group. However, no difference was observed in the consolidation phase. In the working memory task, with inter-trial intervals of 75 min, the escape latency was higher when NI was inactivated in the retrieval phase. In addition, c-fos and pCREB/CREB levels decreased in NI-inhibited rats. This study suggests that nucleus incertus might participate in acquisition of spatial reference, and retrieval of both spatial reference and working memory. Further studies should investigate possible roles of NI in the hippocampal plasticity. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Drug target mining and analysis of the Chinese tree shrew for pharmacological testing.

    Directory of Open Access Journals (Sweden)

    Feng Zhao

    Full Text Available The discovery of new drugs requires the development of improved animal models for drug testing. The Chinese tree shrew is considered to be a realistic candidate model. To assess the potential of the Chinese tree shrew for pharmacological testing, we performed drug target prediction and analysis on genomic and transcriptomic scales. Using our pipeline, 3,482 proteins were predicted to be drug targets. Of these predicted targets, 446 and 1,049 proteins with the highest rank and total scores, respectively, included homologs of targets for cancer chemotherapy, depression, age-related decline and cardiovascular disease. Based on comparative analyses, more than half of drug target proteins identified from the tree shrew genome were shown to be higher similarity to human targets than in the mouse. Target validation also demonstrated that the constitutive expression of the proteinase-activated receptors of tree shrew platelets is similar to that of human platelets but differs from that of mouse platelets. We developed an effective pipeline and search strategy for drug target prediction and the evaluation of model-based target identification for drug testing. This work provides useful information for future studies of the Chinese tree shrew as a source of novel targets for drug discovery research.

  3. Identifying target processes for microbial electrosynthesis by elementary mode analysis.

    Science.gov (United States)

    Kracke, Frauke; Krömer, Jens O

    2014-12-30

    Microbial electrosynthesis and electro fermentation are techniques that aim to optimize microbial production of chemicals and fuels by regulating the cellular redox balance via interaction with electrodes. While the concept is known for decades major knowledge gaps remain, which make it hard to evaluate its biotechnological potential. Here we present an in silico approach to identify beneficial production processes for electro fermentation by elementary mode analysis. Since the fundamentals of electron transport between electrodes and microbes have not been fully uncovered yet, we propose different options and discuss their impact on biomass and product yields. For the first time 20 different valuable products were screened for their potential to show increased yields during anaerobic electrically enhanced fermentation. Surprisingly we found that an increase in product formation by electrical enhancement is not necessarily dependent on the degree of reduction of the product but rather the metabolic pathway it is derived from. We present a variety of beneficial processes with product yield increases of maximal 36% in reductive and 84% in oxidative fermentations and final theoretical product yields up to 100%. This includes compounds that are already produced at industrial scale such as succinic acid, lysine and diaminopentane as well as potential novel bio-commodities such as isoprene, para-hydroxybenzoic acid and para-aminobenzoic acid. Furthermore, it is shown that the way of electron transport has major impact on achievable biomass and product yields. The coupling of electron transport to energy conservation could be identified as crucial for most processes. This study introduces a powerful tool to determine beneficial substrate and product combinations for electro-fermentation. It also highlights that the maximal yield achievable by bio electrochemical techniques depends strongly on the actual electron transport mechanisms. Therefore it is of great importance to

  4. IL26 gene inactivation in Equidae.

    Science.gov (United States)

    Shakhsi-Niaei, M; Drögemüller, M; Jagannathan, V; Gerber, V; Leeb, T

    2013-12-01

    Interleukin-26 (IL26) is a member of the IL10 cytokine family. The IL26 gene is located between two other well-known cytokines genes of this family encoding interferon-gamma (IFNG) and IL22 in an evolutionary conserved gene cluster. In contrast to humans and most other mammals, mice lack a functional Il26 gene. We analyzed the genome sequences of other vertebrates for the presence or absence of functional IL26 orthologs and found that the IL26 gene has also become inactivated in several equid species. We detected a one-base pair frameshift deletion in exon 2 of the IL26 gene in the domestic horse (Equus caballus), Przewalski horse (Equus przewalskii) and donkey (Equus asinus). The remnant IL26 gene in the horse is still transcribed and gives rise to at least five alternative transcripts. None of these transcripts share a conserved open reading frame with the human IL26 gene. A comparative analysis across diverse vertebrates revealed that the IL26 gene has also independently been inactivated in a few other mammals, including the African elephant and the European hedgehog. The IL26 gene thus appears to be highly variable, and the conserved open reading frame has been lost several times during mammalian evolution. © 2013 The Authors, Animal Genetics © 2013 Stichting International Foundation for Animal Genetics.

  5. Identification and analysis of potential targets in Streptococcus sanguinis using computer aided protein data analysis.

    Science.gov (United States)

    Chowdhury, Md Rabiul Hossain; Bhuiyan, Md IqbalKaiser; Saha, Ayan; Mosleh, Ivan Mhai; Mondol, Sobuj; Ahmed, C M Sabbir

    2014-01-01

    Streptococcus sanguinis is a Gram-positive, facultative aerobic bacterium that is a member of the viridans streptococcus group. It is found in human mouths in dental plaque, which accounts for both dental cavities and bacterial endocarditis, and which entails a mortality rate of 25%. Although a range of remedial mediators have been found to control this organism, the effectiveness of agents such as penicillin, amoxicillin, trimethoprim-sulfamethoxazole, and erythromycin, was observed. The emphasis of this investigation was on finding substitute and efficient remedial approaches for the total destruction of this bacterium. In this computational study, various databases and online software were used to ascertain some specific targets of S. sanguinis. Particularly, the Kyoto Encyclopedia of Genes and Genomes databases were applied to determine human nonhomologous proteins, as well as the metabolic pathways involved with those proteins. Different software such as Phyre2, CastP, DoGSiteScorer, the Protein Function Predictor server, and STRING were utilized to evaluate the probable active drug binding site with its known function and protein-protein interaction. In this study, among 218 essential proteins of this pathogenic bacterium, 81 nonhomologous proteins were accrued, and 15 proteins that are unique in several metabolic pathways of S. sanguinis were isolated through metabolic pathway analysis. Furthermore, four essentially membrane-bound unique proteins that are involved in distinct metabolic pathways were revealed by this research. Active sites and druggable pockets of these selected proteins were investigated with bioinformatic techniques. In addition, this study also mentions the activity of those proteins, as well as their interactions with the other proteins. Our findings helped to identify the type of protein to be considered as an efficient drug target. This study will pave the way for researchers to develop and discover more effective and specific

  6. Identification and analysis of potential targets in Streptococcus sanguinis using computer aided protein data analysis

    Science.gov (United States)

    Chowdhury, Md Rabiul Hossain; Bhuiyan, Md IqbalKaiser; Saha, Ayan; Mosleh, Ivan MHAI; Mondol, Sobuj; Ahmed, C M Sabbir

    2014-01-01

    Purpose Streptococcus sanguinis is a Gram-positive, facultative aerobic bacterium that is a member of the viridans streptococcus group. It is found in human mouths in dental plaque, which accounts for both dental cavities and bacterial endocarditis, and which entails a mortality rate of 25%. Although a range of remedial mediators have been found to control this organism, the effectiveness of agents such as penicillin, amoxicillin, trimethoprim–sulfamethoxazole, and erythromycin, was observed. The emphasis of this investigation was on finding substitute and efficient remedial approaches for the total destruction of this bacterium. Materials and methods In this computational study, various databases and online software were used to ascertain some specific targets of S. sanguinis. Particularly, the Kyoto Encyclopedia of Genes and Genomes databases were applied to determine human nonhomologous proteins, as well as the metabolic pathways involved with those proteins. Different software such as Phyre2, CastP, DoGSiteScorer, the Protein Function Predictor server, and STRING were utilized to evaluate the probable active drug binding site with its known function and protein–protein interaction. Results In this study, among 218 essential proteins of this pathogenic bacterium, 81 nonhomologous proteins were accrued, and 15 proteins that are unique in several metabolic pathways of S. sanguinis were isolated through metabolic pathway analysis. Furthermore, four essentially membrane-bound unique proteins that are involved in distinct metabolic pathways were revealed by this research. Active sites and druggable pockets of these selected proteins were investigated with bioinformatic techniques. In addition, this study also mentions the activity of those proteins, as well as their interactions with the other proteins. Conclusion Our findings helped to identify the type of protein to be considered as an efficient drug target. This study will pave the way for researchers to

  7. Identification and analysis of potential targets in Streptococcus sanguinis using computer aided protein data analysis

    Directory of Open Access Journals (Sweden)

    Chowdhury MRH

    2014-11-01

    Full Text Available Md Rabiul Hossain Chowdhury,1 Md IqbalKaiser Bhuiyan,2 Ayan Saha,2 Ivan MHAI Mosleh,2 Sobuj Mondol,2 C M Sabbir Ahmed3 1Department of Pharmacy, University of Science and Technology Chittagong, Chittagong, Bangladesh; 2Department of Genetic Engineering and Biotechnology, University of Chittagong, Chittagong, Bangladesh; 3Biotechnology and Genetic Engineering Discipline, Khulna University, Khulna, Bangladesh Purpose: Streptococcus sanguinis is a Gram-positive, facultative aerobic bacterium that is a member of the viridans streptococcus group. It is found in human mouths in dental plaque, which accounts for both dental cavities and bacterial endocarditis, and which entails a mortality rate of 25%. Although a range of remedial mediators have been found to control this organism, the effectiveness of agents such as penicillin, amoxicillin, trimethoprim–sulfamethoxazole, and erythromycin, was observed. The emphasis of this investigation was on finding substitute and efficient remedial approaches for the total destruction of this bacterium. Materials and methods: In this computational study, various databases and online software were used to ascertain some specific targets of S. sanguinis. Particularly, the Kyoto Encyclopedia of Genes and Genomes databases were applied to determine human nonhomologous proteins, as well as the metabolic pathways involved with those proteins. Different software such as Phyre2, CastP, DoGSiteScorer, the Protein Function Predictor server, and STRING were utilized to evaluate the probable active drug binding site with its known function and protein–protein interaction. Results: In this study, among 218 essential proteins of this pathogenic bacterium, 81 nonhomologous proteins were accrued, and 15 proteins that are unique in several metabolic pathways of S. sanguinis were isolated through metabolic pathway analysis. Furthermore, four essentially membrane-bound unique proteins that are involved in distinct metabolic

  8. Design of the solid target structure and the study on the coolant flow distribution in the solid target using the 2-dimensional flow analysis

    International Nuclear Information System (INIS)

    Haga, Katsuhiro; Terada, Atsuhiko; Ishikura, Shuichi; Teshigawara, Makoto; Kinoshita, Hidetaka; Kobayashi, Kaoru; Kaminaga, Masaki; Hino, Ryutaro; Susuki, Akira

    1999-11-01

    A solid target cooled by heavy water is presently under development under the Neutron Science Research Project of the Japan Atomic Energy Research Institute (JAERI). Target plates of several millimeters thickness made of heavy metal are used as the spallation target material and they are put face to face in a row with one to two millimeters gaps in between though which heavy water flows, as the coolant. Based on the design criteria regarding the target plate cooling, the volume percentage of the coolant, and the thermal stress produced in the target plates, we conducted thermal and hydraulic analysis with a one dimensional target plate model. We choosed tungsten as the target material, and decided on various target plate thicknesses. We then calculated the temperature and the thermal stress in the target plates using a two dimensional model, and confirmed the validity of the target plate thicknesses. Based on these analytical results, we proposed a target structure in which forty target plates are divided into six groups and each group is cooled using a single pass of coolant. In order to investigate the relationship between the distribution of the coolant flow, the pressure drop, and the coolant velocity, we conducted a hydraulic analysis using the general purpose hydraulic analysis code. As a result, we realized that an uniform coolant flow distribution can be achieved under a wide range of flow velocity conditions in the target plate cooling channels from 1 m/s to 10 m/s. The pressure drop along the coolant path was 0.09 MPa and 0.17 MPa when the coolant flow velocity was 5 m/s and 7 m/s respectively, which is required to cool the 1.5 MW and 2.5 MW solid targets. (author)

  9. An assessment of independent component analysis for detection of military targets from hyperspectral images

    Science.gov (United States)

    Tiwari, K. C.; Arora, M. K.; Singh, D.

    2011-10-01

    Hyperspectral data acquired over hundreds of narrow contiguous wavelength bands are extremely suitable for target detection due to their high spectral resolution. Though spectral response of every material is expected to be unique, but in practice, it exhibits variations, which is known as spectral variability. Most target detection algorithms depend on spectral modelling using a priori available target spectra In practice, target spectra is, however, seldom available a priori. Independent component analysis (ICA) is a new evolving technique that aims at finding out components which are statistically independent or as independent as possible. The technique therefore has the potential of being used for target detection applications. A assessment of target detection from hyperspectral images using ICA and other algorithms based on spectral modelling may be of immense interest, since ICA does not require a priori target information. The aim of this paper is, thus, to assess the potential of ICA based algorithm vis a vis other prevailing algorithms for military target detection. Four spectral matching algorithms namely Orthogonal Subspace Projection (OSP), Constrained Energy Minimisation (CEM), Spectral Angle Mapper (SAM) and Spectral Correlation Mapper (SCM), and four anomaly detection algorithms namely OSP anomaly detector (OSPAD), Reed-Xiaoli anomaly detector (RXD), Uniform Target Detector (UTD) and a combination of Reed-Xiaoli anomaly detector and Uniform Target Detector (RXD-UTD) were considered. The experiments were conducted using a set of synthetic and AVIRIS hyperspectral images containing aircrafts as military targets. A comparison of true positive and false positive rates of target detections obtained from ICA and other algorithms plotted on a receiver operating curves (ROC) space indicates the superior performance of the ICA over other algorithms.

  10. Dynamic analysis of the Nova Target Chamber to assess alignment errors due to ambient noise

    International Nuclear Information System (INIS)

    McCallen, D.B.; Murray, R.C.

    1984-01-01

    We performed a study to determine the dynamic behavior of the Nova Target Chamber. We conducted a free vibration analysis to determine the natural frequencies of vibration and the corresponding modeshapes of the target chamber. Utilizing the free vibration results, we performed forced vibration analysis to predict the displacements of the chamber due to ambient vibration. The input support motion for the forced vibration analysis was defined by a white noise acceleration spectrum which was based on previous measurements of ground noise near the Nova site. A special purpose computer program was prepared to process the results of the forced vibration analysis. The program yields distances by which the lines of sight of the various laser beams miss the target as a result of ambient vibrations. We also performed additional estimates of miss distance to provide bounds on the results. A description of the finite element model of the chamber, the input spectrum, and the results of the analyses are included

  11. Sentiment analysis enhancement with target variable in Kumar’s Algorithm

    Science.gov (United States)

    Arman, A. A.; Kawi, A. B.; Hurriyati, R.

    2016-04-01

    Sentiment analysis (also known as opinion mining) refers to the use of text analysis and computational linguistics to identify and extract subjective information in source materials. Sentiment analysis is widely applied to reviews discussion that is being talked in social media for many purposes, ranging from marketing, customer service, or public opinion of public policy. One of the popular algorithm for Sentiment Analysis implementation is Kumar algorithm that developed by Kumar and Sebastian. Kumar algorithm can identify the sentiment score of the statement, sentence or tweet, but cannot determine the relationship of the object or target related to the sentiment being analysed. This research proposed solution for that challenge by adding additional component that represent object or target to the existing algorithm (Kumar algorithm). The result of this research is a modified algorithm that can give sentiment score based on a given object or target.

  12. Design study and heat transfer analysis of a neutron converter target for medical radioisotope production

    International Nuclear Information System (INIS)

    Masoud Behzad; Sang-In Bak; Seung-Woo Hong; Jong-Seo Chai; Yacine Kadi; Claudio Tenreiro; University of Talca, Talca

    2014-01-01

    A worldwide challenge in the near future will be to find a way of producing radioisotopes in sufficient quantity without relying on research reactors. The motivation for this innovative work on targets lies in the accelerator-based production of radioisotopes using a neutron converter target as in the transmutation by adiabatic resonance crossing concept. Thermal analysis of a multi-channel helium cooled device is performed with the computational fluid dynamics code CFX. Different boundary conditions are taken into account in the simulation process and many important parameters such as maximum allowable solid target temperature as well as uniform inlet velocity and outlet pressure changes in the channels are investigated. The results confirm that the cooling configuration works well; hence such a solid target could be operated safely and may be considered for a prototype target. (author)

  13. Cost-effectiveness analysis of intranasal live attenuated vaccine (LAIV versus injectable inactivated influenza vaccine (TIV for Canadian children and adolescents

    Directory of Open Access Journals (Sweden)

    Tarride JE

    2012-10-01

    Full Text Available Jean-Eric Tarride,1,2 Natasha Burke,1,2 Camilla Von Keyserlingk,1,2 Daria O'Reilly,1,2 Feng Xie,1,2 Ron Goeree1,21Programs for Assessment of Technology in Health (PATH Research Institute, St Joseph's Healthcare Hamilton, Hamilton, 2Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, CanadaBackground: Influenza affects all age groups and is common in children. Between 15% and 42% of preschool- and school-aged children experience influenza each season. Recently, intranasal live attenuated influenza vaccine, trivalent (LAIV has been approved in Canada.Objective: The objective of this study was to determine the cost-effectiveness of LAIV compared with that of the injectable inactivated influenza vaccine, trivalent (TIV in Canadian children and adolescents from both a payer (eg. Ministry of Health perspective and a societal perspective.Methods: A cost-effectiveness model comparing LAIV and TIV in children aged 24–59 months old was supplemented by primary (ie, a survey of 144 Canadian physicians and secondary (eg, literature data to model children aged 2–17 years old. Parameter uncertainty was addressed through univariate and probability analyses.Results: Although LAIV increased vaccination costs when compared to TIV, LAIV reduced the number of influenza cases and lowered the number of hospitalizations, emergency room visits, outpatient visits, and parents’ days lost from work. The estimated offsets in direct and societal costs saved were CAD$4.20 and CAD$35.34, respectively, per vaccinated child aged 2–17 years old. When costs and outcomes were considered, LAIV when compared to TIV, was the dominant strategy. At a willingness to pay of CAD$50,000 per quality adjusted life year gained, or CAD$100,000 per quality adjusted life year gained, the probabilistic results indicated that the probability of LAIV being cost-effective was almost 1.Conclusions: LAIV reduces the burden

  14. Analysis of the Neutron Generator and Target for the LSDTS System

    Energy Technology Data Exchange (ETDEWEB)

    Park, Chang Je; Lee, Yong Deok; Song, Jae Hoon; Song, Kee Chan [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2008-11-15

    A preliminary analysis was performed based on the literatures and the patents for the neutron generators and targets for the lead slowing down time spectrometer (LSDTS) system. It was found that local neutron generator did not exhibit enough neutron intensity such as 1E+12 n/s, which is a minimum requirement for the LSDTS system to overcome curium backgrounds. However, a neutron generator implemented with an electron accelerator may provide a higher intensity around 1E+13 n/s and it is required to investigate further including a detail analysis. In addition to the neutron generator, a study on target was performed with the Monte Carlo simulation. In the study, an optimal design of target was suggested to provide a high neutron yield and a better thermal resistance. The suggested target consists several cylindrical plates with a certain cooling gap, which have increasing thickness and increasing radius.

  15. Target preparation and neutron activation analysis a successful story at IRMM

    CERN Document Server

    Robouch, P; Eguskiza, M; Maguregui, M I; Pommé, S; Ingelbrecht, C

    2002-01-01

    The main task of a target producer is to make well characterized and homogeneous deposits on specific supports. Alpha and/or gamma spectrometry are traditionally used to monitor the quality of actinide deposits. With the increasing demand for enriched stable isotope targets, other analytical techniques, such as ICP-MS and NAA, are needed. This paper presents the application of neutron activation analysis to quality control of 'thin' targets, 'thicker' neutron dosimeters and 'thick' bronze disks prepared by the Reference Materials Unit at the Institute of Reference Materials and Measurements.

  16. Target preparation and neutron activation analysis: a successful story at IRMM

    International Nuclear Information System (INIS)

    Robouch, P.; Arana, G.; Eguskiza, M.; Maguregui, M.I.; Pomme, S.; Ingelbrecht, C.

    2002-01-01

    The main task of a target producer is to make well characterized and homogeneous deposits on specific supports. Alpha and/or gamma spectrometry are traditionally used to monitor the quality of actinide deposits. With the increasing demand for enriched stable isotope targets, other analytical techniques, such as ICP-MS and NAA, are needed. This paper presents the application of neutron activation analysis to quality control of 'thin' targets, 'thicker' neutron dosimeters and 'thick' bronze disks prepared by the Reference Materials Unit at the Institute of Reference Materials and Measurements

  17. Anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis show distinct patterns of brain glucose metabolism in 18F-fluoro-2-deoxy-d-glucose positron emission tomography.

    Science.gov (United States)

    Wegner, Florian; Wilke, Florian; Raab, Peter; Tayeb, Said Ben; Boeck, Anna-Lena; Haense, Cathleen; Trebst, Corinna; Voss, Elke; Schrader, Christoph; Logemann, Frank; Ahrens, Jörg; Leffler, Andreas; Rodriguez-Raecke, Rea; Dengler, Reinhard; Geworski, Lilli; Bengel, Frank M; Berding, Georg; Stangel, Martin; Nabavi, Elham

    2014-06-20

    Pathogenic autoantibodies targeting the recently identified leucine rich glioma inactivated 1 protein and the subunit 1 of the N-methyl-D-aspartate receptor induce autoimmune encephalitis. A comparison of brain metabolic patterns in 18F-fluoro-2-deoxy-d-glucose positron emission tomography of anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis patients has not been performed yet and shall be helpful in differentiating these two most common forms of autoimmune encephalitis. The brain 18F-fluoro-2-deoxy-d-glucose uptake from whole-body positron emission tomography of six anti-N-methyl-D-aspartate receptor encephalitis patients and four patients with anti-leucine rich glioma inactivated 1 protein encephalitis admitted to Hannover Medical School between 2008 and 2012 was retrospectively analyzed and compared to matched controls. Group analysis of anti-N-methyl-D-aspartate encephalitis patients demonstrated regionally limited hypermetabolism in frontotemporal areas contrasting an extensive hypometabolism in parietal lobes, whereas the anti-leucine rich glioma inactivated 1 protein syndrome was characterized by hypermetabolism in cerebellar, basal ganglia, occipital and precentral areas and minor frontomesial hypometabolism. This retrospective 18F-fluoro-2-deoxy-d-glucose positron emission tomography study provides novel evidence for distinct brain metabolic patterns in patients with anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis.

  18. Inactivation disinfection property of Moringa Oleifera seed extract: optimization and kinetic studies

    Science.gov (United States)

    Idris, M. A.; Jami, M. S.; Hammed, A. M.

    2017-05-01

    This paper presents the statistical optimization study of disinfection inactivation parameters of defatted Moringa oleifera seed extract on Pseudomonas aeruginosa bacterial cells. Three level factorial design was used to estimate the optimum range and the kinetics of the inactivation process was also carried. The inactivation process involved comparing different disinfection models of Chicks-Watson, Collins-Selleck and Homs models. The results from analysis of variance (ANOVA) of the statistical optimization process revealed that only contact time was significant. The optimum disinfection range of the seed extract was 125 mg/L, 30 minutes and 120rpm agitation. At the optimum dose, the inactivation kinetics followed the Collin-Selleck model with coefficient of determination (R2) of 0.6320. This study is the first of its kind in determining the inactivation kinetics of pseudomonas aeruginosa using the defatted seed extract.

  19. Effective inactivation of a wide range of viruses by pasteurization.

    Science.gov (United States)

    Gröner, Albrecht; Broumis, Connie; Fang, Randel; Nowak, Thomas; Popp, Birgit; Schäfer, Wolfram; Roth, Nathan J

    2018-01-01

    Careful selection and testing of plasma reduces the risk of blood-borne viruses in the starting material for plasma-derived products. Furthermore, effective measures such as pasteurization at 60°C for 10 hours have been implemented in the manufacturing process of therapeutic plasma proteins such as human albumin, coagulation factors, immunoglobulins, and enzyme inhibitors to inactivate blood-borne viruses of concern. A comprehensive compilation of the virus reduction capacity of pasteurization is presented including the effect of stabilizers used to protect the therapeutic protein from modifications during heat treatment. The virus inactivation kinetics of pasteurization for a broad range of viruses were evaluated in the relevant intermediates from more than 15 different plasma manufacturing processes. Studies were carried out under the routine manufacturing target variables, such as temperature and product-specific stabilizer composition. Additional studies were also performed under robustness conditions, that is, outside production specifications. The data demonstrate that pasteurization inactivates a wide range of enveloped and nonenveloped viruses of diverse physicochemical characteristics. After a maximum of 6 hours' incubation, no residual infectivity could be detected for the majority of enveloped viruses. Effective inactivation of a range of nonenveloped viruses, with the exception of nonhuman parvoviruses, was documented. Pasteurization is a very robust and reliable virus inactivation method with a broad effectiveness against known blood-borne pathogens and emerging or potentially emerging viruses. Pasteurization has proven itself to be a highly effective step, in combination with other complementary safety measures, toward assuring the virus safety of final product. © 2017 The Authors Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

  20. Malware Analysis: From Large-Scale Data Triage to Targeted Attack Recognition (Dagstuhl Seminar 17281)

    OpenAIRE

    Zennou, Sarah; Debray, Saumya K.; Dullien, Thomas; Lakhothia, Arun

    2018-01-01

    This report summarizes the program and the outcomes of the Dagstuhl Seminar 17281, entitled "Malware Analysis: From Large-Scale Data Triage to Targeted Attack Recognition". The seminar brought together practitioners and researchers from industry and academia to discuss the state-of-the art in the analysis of malware from both a big data perspective and a fine grained analysis. Obfuscation was also considered. The meeting created new links within this very diverse community.

  1. Meta-Analysis of PECS with Individuals with ASD: Investigation of Targeted versus Non-Targeted Outcomes, Participant Characteristics, and Implementation Phase

    Science.gov (United States)

    Ganz, Jennifer B.; Davis, John L.; Lund, Emily M.; Goodwyn, Fara D.; Simpson, Richard L.

    2012-01-01

    The Picture Exchange Communication System (PECS) is a widely used picture/icon aided augmentative communication system designed for learners with autism and other developmental disorders. This meta-analysis analyzes the extant empirical literature for PECS relative to targeted (functional communication) and non-targeted concomitant outcomes…

  2. The roles of the various plasma agents in the inactivation of bacteria

    International Nuclear Information System (INIS)

    Lu Xinpei; Xiong Qing; Tang Zhiyuan; Xiong Zhilan; Hu Jing; Jiang Zhonghe; Pan Yuan; Ye Tao; Cao Yingguang; Sun Ziyong

    2008-01-01

    The roles of various plasma agents in the inactivation of bacteria have recently been investigated. However, up to now, the effect of the charged particles on the inactivation of bacteria is not well understood. In this paper, an atmospheric pressure plasma jet device, which generates a cold plasma plume carrying a peak current of 300 mA, is used to investigate the role of the charged particles in the inactivation process. It is found that the charged particles play a minor role in the inactivation process when He/N 2 (3%) is used as working gas. On the other hand, when He/O 2 (3%) is used, the charged particles are expected to play an important role in the inactivation of bacteria. Further analysis shows that the negative ions O 2 - might be the charged particles that are playing the role. Besides, it is found that the active species, including O, O 3 , and metastable state O 2 *, can play a crucial role in the inactivation of the bacteria. However, the excited He*, N 2 C 3 Π u , and N 2 + B 2 Σ u + have no significant direct effect on the inactivation of bacteria. It is also concluded that heat and UV play no or minor role in the inactivation process

  3. Inhibition of Retinoblastoma Protein Inactivation

    Science.gov (United States)

    2017-11-01

    CONTRACT NUMBER Inhibition of Retinoblastoma Protein Inactivation 5b. GRANT NUMBER W81XWH-14-1-0329 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Seth M...confirmed 108 compounds as giving a dose-response curve with at least 30% inhibition at 10 µM. The flowchart of hit progression is shown on the...Cancer Research Program under Award No. W81XWH-14-1-0329 to S.M.R. Opinions, interpretations, conclusions, and recommendations are those of the author

  4. Genome-Wide Analysis of miRNA targets in Brachypodium and Biomass Energy Crops

    Energy Technology Data Exchange (ETDEWEB)

    Green, Pamela J. [Univ. of Delaware, Newark, DE (United States)

    2015-08-11

    MicroRNAs (miRNAs) contribute to the control of numerous biological processes through the regulation of specific target mRNAs. Although the identities of these targets are essential to elucidate miRNA function, the targets are much more difficult to identify than the small RNAs themselves. Before this work, we pioneered the genome-wide identification of the targets of Arabidopsis miRNAs using an approach called PARE (German et al., Nature Biotech. 2008; Nature Protocols, 2009). Under this project, we applied PARE to Brachypodium distachyon (Brachypodium), a model plant in the Poaceae family, which includes the major food grain and bioenergy crops. Through in-depth global analysis and examination of specific examples, this research greatly expanded our knowledge of miRNAs and target RNAs of Brachypodium. New regulation in response to environmental stress or tissue type was found, and many new miRNAs were discovered. More than 260 targets of new and known miRNAs with PARE sequences at the precise sites of miRNA-guided cleavage were identified and characterized. Combining PARE data with the small RNA data also identified the miRNAs responsible for initiating approximately 500 phased loci, including one of the novel miRNAs. PARE analysis also revealed that differentially expressed miRNAs in the same family guide specific target RNA cleavage in a correspondingly tissue-preferential manner. The project included generation of small RNA and PARE resources for bioenergy crops, to facilitate ongoing discovery of conserved miRNA-target RNA regulation. By associating specific miRNA-target RNA pairs with known physiological functions, the research provides insights about gene regulation in different tissues and in response to environmental stress. This, and release of new PARE and small RNA data sets should contribute basic knowledge to enhance breeding and may suggest new strategies for improvement of biomass energy crops.

  5. Bioinformatic analysis of xenobiotic reactive metabolite target proteins and their interacting partners

    Directory of Open Access Journals (Sweden)

    Hanzlik Robert P

    2009-06-01

    Full Text Available Abstract Background Protein covalent binding by reactive metabolites of drugs, chemicals and natural products can lead to acute cytotoxicity. Recent rapid progress in reactive metabolite target protein identification has shown that adduction is surprisingly selective and inspired the hope that analysis of target proteins might reveal protein factors that differentiate target- vs. non-target proteins and illuminate mechanisms connecting covalent binding to cytotoxicity. Results Sorting 171 known reactive metabolite target proteins revealed a number of GO categories and KEGG pathways to be significantly enriched in targets, but in most cases the classes were too large, and the "percent coverage" too small, to allow meaningful conclusions about mechanisms of toxicity. However, a similar analysis of the directlyinteracting partners of 28 common targets of multiple reactive metabolites revealed highly significant enrichments in terms likely to be highly relevant to cytotoxicity (e.g., MAP kinase pathways, apoptosis, response to unfolded protein. Machine learning was used to rank the contribution of 211 computed protein features to determining protein susceptibility to adduction. Protein lysine (but not cysteine content and protein instability index (i.e., rate of turnover in vivo were among the features most important to determining susceptibility. Conclusion As yet there is no good explanation for why some low-abundance proteins become heavily adducted while some abundant proteins become only lightly adducted in vivo. Analyzing the directly interacting partners of target proteins appears to yield greater insight into mechanisms of toxicity than analyzing target proteins per se. The insights provided can readily be formulated as hypotheses to test in future experimental studies.

  6. Numerical analysis of free surface instabilities in the IFMIF lithium target

    International Nuclear Information System (INIS)

    Gordeev, S.; Heinzel, V.; Moeslang, A.

    2007-01-01

    The International Fusion Materials Facility (IFMIF) facility uses a high speed (10-20 m/s) Lithium (Li) jet flow as a target for two 40 MeV/125 mA deuteron beams. The major function of the Li target is to provide a stable Li jet for the production of an intense neutron flux. For the understanding the lithium jet behaviour and elimination of the free-surface flow instabilities a detailed analysis of the Li jet flow is necessary. Different kinds of instability mechanisms in the liquid jet flow have been evaluated and classified based on analytical and experimental data. Numerical investigations of the target free surface flow have been performed. Previous numerical investigations have shown in principle the suitability of CFD code Star- CD for the simulation of the Li-target flow. The main objective of this study is detailed numerical analysis of instabilities in the Li-jet flow caused by boundary layer relaxation near the nozzle exit, transition to the turbulence flow and back wall curvature. A number of CFD models are developed to investigate the formation of instabilities on the target surface. Turbulence models are validated on the experimental data. Experimental observations have shown that the change of the nozzle geometry at the outlet such as a slight divergence of the nozzle surfaces or nozzle edge defects causes the flow separation and occurrence of longitudinal periodic structures on the free surface with an amplitude up to 5 mm. Target surface fluctuations of this magnitude can lead to the penetration of the deuteron beam in the target structure and cause the local overheating of the back plat. Analysis of large instabilities in the Li-target flow combined with the heat distribution in lithium depending on the free surface shape is performed in this study. (orig.)

  7. Problem-Solving Test: Targeted Gene Disruption

    Science.gov (United States)

    Szeberenyi, Jozsef

    2008-01-01

    Mutational inactivation of a specific gene is the most powerful technique to analyze the biological function of the gene. This approach has been used for a long time in viruses, bacteria, yeast, and fruit fly, but looked quite hopeless in more complex organisms. Targeted inactivation of specific genes (also known as knock-out mutation) in mice is…

  8. Effective hepatitis A virus inactivation during low-heat dehydration of contaminated green onions.

    Science.gov (United States)

    Laird, David T; Sun, Yan; Reineke, Karl F; Shieh, Y Carol

    2011-08-01

    Preserving fruits and vegetables by dehydration is common; however, information is limited concerning viral survival on the produce during the process. This work demonstrated the effects of low heat dehydration on inactivating hepatitis A virus (HAV) on contaminated green onions. Inoculated and uninoculated onion samples were dehydrated at target temperatures of 45-65 °C for 20 h. HAV from artificially contaminated onions (fresh or dehydrated) was eluted by shaking at 145 rpm at 20 °C for 20 min with 3% beef extract, pH 8, and followed by 0.2 μM-membrane filtration before plaque assay and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. Dilutions of the filtrates were made for obtaining countable plaques on FRhK-4 cell monolayers in 6-well plates, and also for eliminating inhibitors in qRT-PCR. Average water activity of the onions after 20 h-dehydration was 0.227, regardless of temperature used (47.9 °C or 65.1 °C). Eight dehydration trials resulted in a linear relationship between HAV inactivation and dehydration temperature, with HAV log reduction = 0.1372x(°C) - 5.5572, r(2) = 0.88. Therefore, the 20 h-heating at 47.8, 55.1, and 62.4 °C reduced infectious HAV in onions by 1, 2, and 3 logs respectively, the Z value being 7.3 °C. It was concluded that low heat dehydration using 62.5 °C or above could effectively inactivate HAV on contaminated onions by >3 logs. Published by Elsevier Ltd.

  9. Inference of miRNA targets using evolutionary conservation and pathway analysis

    Directory of Open Access Journals (Sweden)

    van Nimwegen Erik

    2007-03-01

    assigns a posterior probability to each putative target site. The results presented here indicate that our general method achieves very good performance in predicting miRNA target sites, providing at the same time insights into the evolution of target sites for individual miRNAs. Moreover, by combining our predictions with pathway analysis, we propose functions of specific miRNAs in nervous system development, inter-cellular communication and cell growth. The complete target site predictions as well as the miRNA/pathway associations are accessible on the ElMMo web server.

  10. Thermal analysis of Ti drive-in target for D-D neutron generation

    International Nuclear Information System (INIS)

    Jung, N.S.; Kim, I.J.; Kim, S.J.; Choi, H.D.

    2008-01-01

    Full text: Thermal analysis was performed for a Ti drive-in target of a D-D neutron generator. Numerical calculation was the only feasible way to obtain the information of the target temperature, since it was very difficult to measure the target temperature during neutron generation due to high voltage being applied to the target. Computational fluid dynamics code CFX-5 was used in this study. In order to define the heat flux term for the thermal analysis, the current profile of the ion beam was measured. The one-dimensional, integrated current profile was measured by using a single slit and a Faraday cup. The measured current profile was transformed into the axially symmetric two-dimensional distribution function by using the Abel inversion, which had the two-dimensional Gaussian function shape. Temperature distribution in the target was calculated at the operating condition. The influence of operational parameters like the ion beam energy, current, coolant mass flow rate and coolant inlet temperature on the target temperature was investigated

  11. Positioning accuracy analysis of adjusting target mechanism of three-dimensional attitude

    International Nuclear Information System (INIS)

    Ma Li; Wang Kun; Sun Linzhi; Zhou Shasha

    2012-01-01

    A novel adjusting target mechanism of three-dimensional attitude is presented according to the characteristics of the target transport subsystem in inertial confinement fusion (ICF). The mechanism consists of a tangent mechanism adjusting rotation angle and a set of orthogonal tangent mechanism adjusting two-dimensional deflection angles. The structural parameters of the adjusting target mechanism are analyzed according to principle errors, structure errors and motion errors of following. The analysis results indicate that the system error of the adjusting target mechanism is influenced by the displacement of the linear actuators, the actuator ball radius, the working radius of the tangent mechanism, the angle error of the inclined installation hole, the centralization error of the actuators, the orthogonal error of the two tangent mechanism, and the angle errors of the inclined target rod inclined rotation shaft. The errors of the inclined target rod and inclined rotation shaft are the two greatest impact factors, the spherical contact error is the next. By means of precise assembly and control system compensation, the accuracy of the adjusting target mechanism can be less than 0.1 mrad. (authors)

  12. A model for the stepwise radiation inactivation of the alpha 2-dimer of Na,K-ATPase

    Energy Technology Data Exchange (ETDEWEB)

    Norby, J.G.; Jensen, J. (Univ. of Aarhus (Denmark))

    1989-11-25

    This study is a direct continuation of Jensen, J., and Norby. A new model in which we propose that the in situ organization of the Na,K-ATPase alpha-subunit is an alpha 2-dimer and which describes the stepwise degradation by radiation inactivation of this assembly is presented on the basis of the following findings. Radiation inactivation size for alpha-peptide integrity, normal nucleotide, vanadate and ouabain binding, and K-pNPPase activity is close to m(alpha) = 112 kDa; for Na-ATPase activity it is 135 kDa and for Na,K-ATPase activity it increases from 140 to about 195 kDa with increasing assay ATP concentration (equal to increasing average turnover). Normal Tl+ occlusion had the same radiation inactivation size as Vmax for Na,K-ATPase, i.e. about 195 kDa. The binding experiments disclosed radiation-produced molecules with active binding sites but with a lower than normal affinity. Radiation inactivation size for the total binding capacity of ADP and ouabain was therefore smaller than the size of an alpha-peptide, namely about 70 kDa, and for total Tl+ occlusion it was down to 40 kDa. We can explain all these observations by using a new approach to target size analysis and by assuming a dimeric organization of the alpha-subunit. Each alpha-peptide is degraded stepwise by first destruction of either a 42- or a 70-kDa domain, and the partly damaged peptide may retain biochemical activity. We conclude that there is no role for the beta-subunit in catalysis and that the alpha-peptide is organized as an alpha 2-dimer in the membrane with each alpha-subunit being able to perform complete catalytic cycles (and probably also active transport), provided that it is stabilized by an adjacent alpha-peptide or a sufficiently large fragment thereof.

  13. A model for the stepwise radiation inactivation of the alpha 2-dimer of Na,K-ATPase

    International Nuclear Information System (INIS)

    Norby, J.G.; Jensen, J.

    1989-01-01

    This study is a direct continuation of Jensen, J., and Norby. A new model in which we propose that the in situ organization of the Na,K-ATPase alpha-subunit is an alpha 2-dimer and which describes the stepwise degradation by radiation inactivation of this assembly is presented on the basis of the following findings. Radiation inactivation size for alpha-peptide integrity, normal nucleotide, vanadate and ouabain binding, and K-pNPPase activity is close to m(alpha) = 112 kDa; for Na-ATPase activity it is 135 kDa and for Na,K-ATPase activity it increases from 140 to about 195 kDa with increasing assay ATP concentration (equal to increasing average turnover). Normal Tl+ occlusion had the same radiation inactivation size as Vmax for Na,K-ATPase, i.e. about 195 kDa. The binding experiments disclosed radiation-produced molecules with active binding sites but with a lower than normal affinity. Radiation inactivation size for the total binding capacity of ADP and ouabain was therefore smaller than the size of an alpha-peptide, namely about 70 kDa, and for total Tl+ occlusion it was down to 40 kDa. We can explain all these observations by using a new approach to target size analysis and by assuming a dimeric organization of the alpha-subunit. Each alpha-peptide is degraded stepwise by first destruction of either a 42- or a 70-kDa domain, and the partly damaged peptide may retain biochemical activity. We conclude that there is no role for the beta-subunit in catalysis and that the alpha-peptide is organized as an alpha 2-dimer in the membrane with each alpha-subunit being able to perform complete catalytic cycles (and probably also active transport), provided that it is stabilized by an adjacent alpha-peptide or a sufficiently large fragment thereof

  14. Cell cloning-based transcriptome analysis in Rett patients: relevance to the pathogenesis of Rett syndrome of new human MeCP2 target genes.

    Science.gov (United States)

    Nectoux, J; Fichou, Y; Rosas-Vargas, H; Cagnard, N; Bahi-Buisson, N; Nusbaum, P; Letourneur, F; Chelly, J; Bienvenu, T

    2010-07-01

    More than 90% of Rett syndrome (RTT) patients have heterozygous mutations in the X-linked methyl-CpG binding protein 2 (MECP2) gene that encodes the methyl-CpG-binding protein 2, a transcriptional modulator. Because MECP2 is subjected to X chromosome inactivation (XCI), girls with RTT either express the wild-type or mutant allele in each individual cell. To test the consequences of MECP2 mutations resulting from a genome-wide transcriptional dysregulation and to identify its target genes in a system that circumvents the functional mosaicism resulting from XCI, we carried out gene expression profiling of clonal populations derived from fibroblast primary cultures expressing exclusively either the wild-type or the mutant MECP2 allele. Clonal cultures were obtained from skin biopsy of three RTT patients carrying either a non-sense or a frameshift MECP2 mutation. For each patient, gene expression profiles of wild-type and mutant clones were compared by oligonucleotide expression microarray analysis. Firstly, clustering analysis classified the RTT patients according to their genetic background and MECP2 mutation. Secondly, expression profiling by microarray analysis and quantitative RT-PCR indicated four up-regulated genes and five down-regulated genes significantly dysregulated in all our statistical analysis, including excellent potential candidate genes for the understanding of the pathophysiology of this neurodevelopmental disease. Thirdly, chromatin immunoprecipitation analysis confirmed MeCP2 binding to respective CpG islands in three out of four up-regulated candidate genes and sequencing of bisulphite-converted DNA indicated that MeCP2 preferentially binds to methylated-DNA sequences. Most importantly, the finding that at least two of these genes (BMCC1 and RNF182) were shown to be involved in cell survival and/or apoptosis may suggest that impaired MeCP2 function could alter the survival of neurons thus compromising brain function without inducing cell death.

  15. TRAC analysis of design basis events for the accelerator production of tritium target/blanket

    International Nuclear Information System (INIS)

    Lin, J.C.; Elson, J.

    1997-01-01

    A two-loop primary cooling system with a residual heat removal system was designed to mitigate the heat generated in the tungsten neutron source rods inside the rungs of the ladders and the shell of the rungs. The Transient Reactor Analysis Code (TRAC) was used to analyze the thermal-hydraulic behavior of the primary cooling system during a pump coastdown transient; a cold-leg, large-break loss-of-coolant accident (LBLOCA); a hot-leg LBLOCA; and a target downcomer LBLOCA. The TRAC analysis results showed that the heat generated in the tungsten neutron source rods can be mitigated by the primary cooling system for the pump coastdown transient and all the LBLOCAs except the target downcomer LBLOCA. For the target downcomer LBLOCA, a cavity flood system is required to fill the cavity with water at a level above the large fixed headers

  16. School programs targeting stress management in children and adolescence: a meta-analysis

    NARCIS (Netherlands)

    Kraag, G.C; Zeegers, M.P.; Kok, G.J.; Hosman, C.M.H.; Huijer Abu-Saad, H.

    2006-01-01

    Introduction This meta-analysis evaluates the effect of school programs targeting stress management or coping skills in school children. Methods Articles were selected through a systematic literature search. Only randomized controlled trials or quasi-experimental studies were included. The

  17. Simulating Serial-Target Antibacterial Drug Synergies Using Flux Balance Analysis

    DEFF Research Database (Denmark)

    Krueger, Andrew S.; Munck, Christian; Dantas, Gautam

    2016-01-01

    Flux balance analysis (FBA) is an increasingly useful approach for modeling the behavior of metabolic systems. However, standard FBA modeling of genetic knockouts cannot predict drug combination synergies observed between serial metabolic targets, even though such synergies give rise to some of t...

  18. Analysis of shots on target and goals scored in soccer matches ...

    African Journals Online (AJOL)

    The aim of this study was to analyse the characteristics and patterns of shots on target and goals scored during the 2012-European Championship. The broadcasted matches were recorded and converted into electronic video files for a computerbased analysis. This quantitative study examined 31 matches of the ...

  19. Doing Televised Rhetorical Analysis as a Means of Promoting College Awareness in a Target Market.

    Science.gov (United States)

    Schnell, Jim

    This paper describes aspects of doing televised rhetorical analysis as they relate to the promotion of college awareness in a particular target market. Considerations in the paper include variables that most professors encounter in their efforts to address the "service" expectations of their employment and how these variables can be…

  20. Radiobiological inactivation of Epstein-Barr virus

    International Nuclear Information System (INIS)

    Henderson, E.; Heston, L.; Grogan, E.; Miller, G.

    1978-01-01

    Lymphocyte transforming properties of B95-8 strain Epstein-Barr virus (EBV) are very sensitive to inactivation by either uv or x irradiation. No dose of irradiation increases the transforming capacity of EBV. The x-ray dose needed for inactivation of EBV transformation (dose that results in 37% survival, 60,000 rads) is similar to the dose required for inactivation of plaque formation by herpes simplex virus type 1 (Fischer strain). Although herpes simplex virus is more sensitive than EBV to uv irradiation, this difference is most likely due to differences in the kinetics or mechanisms of repair of uv damage to the two viruses. The results lead to the hypothesis that a large part, or perhaps all, of the EBV genome is in some way needed to initiate transformation. The abilities of EBV to stimulate host cell DNA synthesis, to induce nuclear antigen, and to immortalize are inactivated in parallel. All clones of marmoset cells transformed by irradiated virus produce extracellular transforming virus. These findings suggest that the abilities of the virus to transform and to replicate complete progeny are inactivated together. The amounts of uv and x irradiation that inactivate transformation by B95-8 virus are less than the dose needed to inactivate early antigen induction by the nontransforming P 3 HR-1 strain of EBV. Based on radiobiological inactivation, 10 to 50% of the genome is needed for early antigen induction

  1. Analysis of Deregulated microRNAs and Their Target Genes in Gastric Cancer.

    Directory of Open Access Journals (Sweden)

    Simonas Juzėnas

    Full Text Available MicroRNAs (miRNAs are widely studied non-coding RNAs that modulate gene expression. MiRNAs are deregulated in different tumors including gastric cancer (GC and have potential diagnostic and prognostic implications. The aim of our study was to determine miRNA profile in GC tissues, followed by evaluation of deregulated miRNAs in plasma of GC patients. Using available databases and bioinformatics methods we also aimed to evaluate potential target genes of confirmed differentially expressed miRNA and validate these findings in GC tissues.The study included 51 GC patients and 51 controls. Initially, we screened miRNA expression profile in 13 tissue samples of GC and 12 normal gastric tissues with TaqMan low density array (TLDA. In the second stage, differentially expressed miRNAs were validated in a replication cohort using qRT-PCR in tissue and plasma samples. Subsequently, we analyzed potential target genes of deregulated miRNAs using bioinformatics approach, determined their expression in GC tissues and performed correlation analysis with targeting miRNAs.Profiling with TLDA revealed 15 deregulated miRNAs in GC tissues compared to normal gastric mucosa. Replication analysis confirmed that miR-148a-3p, miR-204-5p, miR-223-3p and miR-375 were consistently deregulated in GC tissues. Analysis of GC patients' plasma samples showed significant down-regulation of miR-148a-3p, miR-375 and up-regulation of miR-223-3p compared to healthy subjects. Further, using bioinformatic tools we identified targets of replicated miRNAs and performed disease-associated gene enrichment analysis. Ultimately, we evaluated potential target gene BCL2 and DNMT3B expression by qRT-PCR in GC tissue, which correlated with targeting miRNA expression.Our study revealed miRNA profile in GC tissues and showed that miR-148a-3p, miR-223-3p and miR-375 are deregulated in GC plasma samples, but these circulating miRNAs showed relatively weak diagnostic performance as sole biomarkers

  2. Improved target detection and bearing estimation utilizing fast orthogonal search for real-time spectral analysis

    International Nuclear Information System (INIS)

    Osman, Abdalla; El-Sheimy, Naser; Nourledin, Aboelamgd; Theriault, Jim; Campbell, Scott

    2009-01-01

    The problem of target detection and tracking in the ocean environment has attracted considerable attention due to its importance in military and civilian applications. Sonobuoys are one of the capable passive sonar systems used in underwater target detection. Target detection and bearing estimation are mainly obtained through spectral analysis of received signals. The frequency resolution introduced by current techniques is limited which affects the accuracy of target detection and bearing estimation at a relatively low signal-to-noise ratio (SNR). This research investigates the development of a bearing estimation method using fast orthogonal search (FOS) for enhanced spectral estimation. FOS is employed in this research in order to improve both target detection and bearing estimation in the case of low SNR inputs. The proposed methods were tested using simulated data developed for two different scenarios under different underwater environmental conditions. The results show that the proposed method is capable of enhancing the accuracy for target detection as well as bearing estimation especially in cases of a very low SNR

  3. Interacting with target tracking algorithms in a gaze-enhanced motion video analysis system

    Science.gov (United States)

    Hild, Jutta; Krüger, Wolfgang; Heinze, Norbert; Peinsipp-Byma, Elisabeth; Beyerer, Jürgen

    2016-05-01

    Motion video analysis is a challenging task, particularly if real-time analysis is required. It is therefore an important issue how to provide suitable assistance for the human operator. Given that the use of customized video analysis systems is more and more established, one supporting measure is to provide system functions which perform subtasks of the analysis. Recent progress in the development of automated image exploitation algorithms allow, e.g., real-time moving target tracking. Another supporting measure is to provide a user interface which strives to reduce the perceptual, cognitive and motor load of the human operator for example by incorporating the operator's visual focus of attention. A gaze-enhanced user interface is able to help here. This work extends prior work on automated target recognition, segmentation, and tracking algorithms as well as about the benefits of a gaze-enhanced user interface for interaction with moving targets. We also propose a prototypical system design aiming to combine both the qualities of the human observer's perception and the automated algorithms in order to improve the overall performance of a real-time video analysis system. In this contribution, we address two novel issues analyzing gaze-based interaction with target tracking algorithms. The first issue extends the gaze-based triggering of a target tracking process, e.g., investigating how to best relaunch in the case of track loss. The second issue addresses the initialization of tracking algorithms without motion segmentation where the operator has to provide the system with the object's image region in order to start the tracking algorithm.

  4. The Wnt Transcriptional Switch: TLE Removal or Inactivation?

    Science.gov (United States)

    Ramakrishnan, Aravinda-Bharathi; Sinha, Abhishek; Fan, Vinson B; Cadigan, Ken M

    2018-02-01

    Many targets of the Wnt/β-catenin signaling pathway are regulated by TCF transcription factors, which play important roles in animal development, stem cell biology, and oncogenesis. TCFs can regulate Wnt targets through a "transcriptional switch," repressing gene expression in unstimulated cells and promoting transcription upon Wnt signaling. However, it is not clear whether this switch mechanism is a general feature of Wnt gene regulation or limited to a subset of Wnt targets. Co-repressors of the TLE family are known to contribute to the repression of Wnt targets in the absence of signaling, but how they are inactivated or displaced by Wnt signaling is poorly understood. In this mini-review, we discuss several recent reports that address the prevalence and molecular mechanisms of the Wnt transcription switch, including the finding of Wnt-dependent ubiquitination/inactivation of TLEs. Together, these findings highlight the growing complexity of the regulation of gene expression by the Wnt pathway. © 2017 WILEY Periodicals, Inc.

  5. Virtual diplomacy: an analysis of the structure of the target audiences

    Directory of Open Access Journals (Sweden)

    V. V. Verbytska

    2016-03-01

    Full Text Available In the context of the global information society the communication processes, especially at the international level, become more important.  The effectiveness of communication depends primarily on its focus, i.e. on defining clearly the target audience which it should focus on. Virtual diplomacy, as a kind of political communication at the international level, is no exception.  The novelty, rapid development and dissemination of this phenomenon require profound analysis and elaboration of effective utilization strategies, including studying its recipients and target audiences. Purpose: identification, structuring and analysis of the recipients of virtual diplomacy as the audiences of international political communication. The study uses such research methods, as system analysis, structural functionalism, dialectics and synergy, comparison, critical analysis. Main results of the research: 1. The study examined the specifics of political communication in the context of the development of the global information society at the international level. 2. It also analyzed the recipients of virtual diplomacy as a kind of political communication at the international level. 3. The study highlighted the key target groups in the global Internet network based on the tasks performed by virtual diplomacy. 4. It proved the effectiveness of cooperation with each target group in the framework of virtual diplomacy. 5. It described the specifics of the work with each target group in the context of virtual diplomacy. Practical implications: The article may be useful for writing scientific theoretical studies, tests, essays and term papers, for designing special courses in universities in the sphere of international relations and international information. It can also be a guide for the authorities carrying out diplomatic activities and international information cooperation. Findings: In the context of the establishment of the global information society political

  6. System for automatic x-ray-image analysis, measurement, and sorting of laser fusion targets

    International Nuclear Information System (INIS)

    Singleton, R.M.; Perkins, D.E.; Willenborg, D.L.

    1980-01-01

    This paper describes the Automatic X-Ray Image Analysis and Sorting (AXIAS) system which is designed to analyze and measure x-ray images of opaque hollow microspheres used as laser fusion targets. The x-ray images are first recorded on a high resolution film plate. The AXIAS system then digitizes and processes the images to accurately measure the target parameters and defects. The primary goals of the AXIAS system are: to provide extremely accurate and rapid measurements, to engineer a practical system for a routine production environment and to furnish the capability of automatically measuring an array of images for sorting and selection

  7. An analysis of health promotion materials for Dutch truck drivers: Off target and too complex?

    Science.gov (United States)

    Boeijinga, Anniek; Hoeken, Hans; Sanders, José

    2017-01-01

    Despite various health promotion initiatives, unfavorable figures regarding Dutch truck drivers' eating behaviors, exercise behaviors, and absenteeism have not improved. The aim was to obtain a better understanding of the low level of effectiveness of current health interventions for Dutch truck drivers by examining to what extent these are tailored to the target group's particular mindset (focus of content) and health literacy skills (presentation of content). The article analyzes 21 health promotion materials for Dutch truck drivers using a two-step approach: (a) an analysis of the materials' focus, guided by the Health Action Process Approach; and (b) an argumentation analysis, guided by pragma-dialectics. The corpus analysis revealed: (a) a predominant focus on the motivation phase; and (b) in line with the aim of motivating the target group, a consistent use of pragmatic arguments, which were typically presented in an implicit way. The results indicate that existing health promotion materials for Dutch truck drivers are not sufficiently tailored to the target group's mindset and health literacy skills. Recommendations are offered to develop more tailored/effective health interventions targeting this high-risk, underserved occupational group.

  8. TargetVue: Visual Analysis of Anomalous User Behaviors in Online Communication Systems.

    Science.gov (United States)

    Cao, Nan; Shi, Conglei; Lin, Sabrina; Lu, Jie; Lin, Yu-Ru; Lin, Ching-Yung

    2016-01-01

    Users with anomalous behaviors in online communication systems (e.g. email and social medial platforms) are potential threats to society. Automated anomaly detection based on advanced machine learning techniques has been developed to combat this issue; challenges remain, though, due to the difficulty of obtaining proper ground truth for model training and evaluation. Therefore, substantial human judgment on the automated analysis results is often required to better adjust the performance of anomaly detection. Unfortunately, techniques that allow users to understand the analysis results more efficiently, to make a confident judgment about anomalies, and to explore data in their context, are still lacking. In this paper, we propose a novel visual analysis system, TargetVue, which detects anomalous users via an unsupervised learning model and visualizes the behaviors of suspicious users in behavior-rich context through novel visualization designs and multiple coordinated contextual views. Particularly, TargetVue incorporates three new ego-centric glyphs to visually summarize a user's behaviors which effectively present the user's communication activities, features, and social interactions. An efficient layout method is proposed to place these glyphs on a triangle grid, which captures similarities among users and facilitates comparisons of behaviors of different users. We demonstrate the power of TargetVue through its application in a social bot detection challenge using Twitter data, a case study based on email records, and an interview with expert users. Our evaluation shows that TargetVue is beneficial to the detection of users with anomalous communication behaviors.

  9. Hot-spot analysis for drug discovery targeting protein-protein interactions.

    Science.gov (United States)

    Rosell, Mireia; Fernández-Recio, Juan

    2018-04-01

    Protein-protein interactions are important for biological processes and pathological situations, and are attractive targets for drug discovery. However, rational drug design targeting protein-protein interactions is still highly challenging. Hot-spot residues are seen as the best option to target such interactions, but their identification requires detailed structural and energetic characterization, which is only available for a tiny fraction of protein interactions. Areas covered: In this review, the authors cover a variety of computational methods that have been reported for the energetic analysis of protein-protein interfaces in search of hot-spots, and the structural modeling of protein-protein complexes by docking. This can help to rationalize the discovery of small-molecule inhibitors of protein-protein interfaces of therapeutic interest. Computational analysis and docking can help to locate the interface, molecular dynamics can be used to find suitable cavities, and hot-spot predictions can focus the search for inhibitors of protein-protein interactions. Expert opinion: A major difficulty for applying rational drug design methods to protein-protein interactions is that in the majority of cases the complex structure is not available. Fortunately, computational docking can complement experimental data. An interesting aspect to explore in the future is the integration of these strategies for targeting PPIs with large-scale mutational analysis.

  10. Inactivation of 1-aminocyclopropane-1-carboxylate oxidase involves oxidative modifications.

    Science.gov (United States)

    Barlow, J N; Zhang, Z; John, P; Baldwin, J E; Schofield, C J

    1997-03-25

    1-Aminocyclopropane-1-carboxylate (ACC) oxidase catalyzes the final step in the biosynthesis of the plant signaling molecule ethylene. It is a member of the ferrous iron dependent family of oxidases and dioxygenases and is unusual in that it displays a very short half-life under catalytic conditions, typically less than 20 min, and a requirement for CO2 as an activator. The rates of inactivation of purified, recombinant ACC oxidase from tomato under various combinations of substrates and cofactors were measured. Inactivation was relatively slow in the presence of buffer alone (t1/2 > 1 h), but fast in the presence of ferrous iron and ascorbate (t1/2 approximately 10 min). The rate of iron/ascorbate-mediated inactivation was increased by the addition of ACC, unaffected by the addition of CO2 at saturation (supplied as bicarbonate) but decreased by the addition of catalase or ACC + CO2 at saturation (supplied as bicarbonate). Iron/ascorbate-mediated inactivation was accompanied by partial proteolysis as observed by SDS-PAGE analysis. The fragmentation pattern was altered when ACC was also included, suggesting that ACC can bind to ACC oxidase in the absence of bicarbonate. N-terminal sequencing of fragments resulted in identification of an internal cleavage site which we propose is proximate to active-site bound iron. Thus, ACC oxidase inactivates via relatively slow partial unfolding of the catalytically active conformation, oxidative damage mediated via hydrogen peroxide which is catalase protectable and oxidative damage to the active site which results in partial proteolysis and is not catalase protectable.

  11. Analysis of protective and cytotoxic immune responses in vivo against metabolically inactivated and untreated cells of a mutagenized tumor line (requirements for tumor immunogenicity)

    International Nuclear Information System (INIS)

    Wehrmaker, A.; Lehmann, V.; Droege, W.

    1986-01-01

    The immunogenicity of a mutagenized subline (ESb-D) of the weakly immunogenic T-cell lymphoma L 5178 Y ESb has been characterized. The injection of 10(6) ESb-D cells ip did not establish lethal tumors in untreated DBA/2 mice but established tumors in sublethally irradiated mice. Injection of ESb-D cells into otherwise untreated DBA/2 mice established also a state of protective immunity against the subsequent injection of otherwise lethal doses of ESb tumor cells. Protection was only obtained after injection of intact but not UV-irradiated or mitomycin-C-treated ESb-D cells. A direct T-cell-mediated cytotoxic activity was also demonstrable in the spleen cells of DBA/2 mice after injection of ESb-D cells but not ESb cells. The cytotoxic activity was variant specific for ESb-D target cells, and it was induced only with intact but not UV-irradiated or mitomycin C-treated ESb-D cells. This suggested that the induction of protective and cytotoxic immunity may require the persistence of the antigen or unusually high antigen doses. The in vivo priming for a secondary in vitro cytotoxic response, in contrast, was achieved with intact and also with mitomycin C-treated ESb-D cells but again not with UV-irradiated ESb-D cells. This indicated that the metabolic activity was a minimal requirement for the in vivo immunogenicity of the ESb-D tumor line. The secondary cytotoxic activity was demonstrable on ESb-D and ESb target cells and could be restimulated in vitro about equally well with ESb-D and ESb cells. But the in vivo priming was again only obtained with ESb-D cells and not with ESb cells. These experiments thus demonstrated that the requirements for immunogenicity are more stringent in vivo than in vitro, and more stringent for the induction of direct cytotoxic and protective immunity in vivo than for the in vivo priming for secondary in vitro responses

  12. Inactivation of bacterial cells by cyclotron beams

    Energy Technology Data Exchange (ETDEWEB)

    Yatagai, F [Waseda Univ., Tokyo (Japan). School of Science and Engineering; Takahashi, T; Matsuyama, A

    1975-06-01

    B. subtilis spores, E. coli Bsub(s-1) and E. coli B/r were bombarded with ..cap alpha..-particles and heavy ions of carbon, nitrogen and oxygen accelerated in the IPCR Cyclotron. The RBE versus LETsub(infinity) curve for B. subtilis spores showed a maximum peak at 120 keV/..mu..m, while those for E. coli Bsub(s-1) and E. coli B/r declined without any maximum as LETsub(infinity) values increased. In the region of ..cap alpha..-particles, the effective inactivation cross section (Ssub(eff)) for these three strains increased with increasing LETsub(infinity), and the rates of increase in Ssub(eff) in the LET region from --30 to --150 keV/..mu..m were 15.0, 1.5 and 2.5 times for B. subtilis spores, E. coli Bsub(s-1) and E. coli B/r, respectively. In the case of B. subtilis spores, Ssub(eff) values for heavy ions were almost independent of their energies, but the other two strains showed a considerable dependence upon beam energy. The characteristic LET dependence of Ssub(eff) observed in this study was fairly well explained by the target theory based on microdose concept.

  13. Inactivation of bacterial cells by cyclotron beams

    International Nuclear Information System (INIS)

    Yatagai, Fumio; Takahashi, Tadashi; Matsuyama, Akira.

    1975-01-01

    B. subtilis spores, E. coli Bsub(s-1) and E. coli B/r were bombarded with α-particles and heavy ions of carbon, nitrogen and oxygen accelerated in the IPCR Cyclotron. The RBE versus LETsub(infinity) curve for B. subtilis spores showed a maximum peak at 120 keV/μm, while those for E. coli Bsub(s-1) and E. coli B/r declined without any maximum as LETsub(infinity) values increased. In the region of α-particles, the effective inactivation cross section (Ssub(eff)) for these three strains increased with increasing LETsub(infinity), and the rates of increase in Ssub(eff) in the LET region from --30 to --150 keV/μm were 15.0, 1.5 and 2.5 times for B. subtilis spores, E. coli Bsub(s-1) and E. coli B/r, respectively. In the case of B. subtilis spores, Ssub(eff) values for heavy ions were almost independent of their energies, but the other two strains showed a considerable dependence upon beam energy. The characteristic LET dependence of Ssub(eff) observed in this study was fairly well explained by the target theory based on microdose concept. (auth.)

  14. CFD Analysis of the Active Part of the HYPER Spallation Target

    International Nuclear Information System (INIS)

    Nam-il Tak; Chungho Cho; Tae-Yung Song

    2006-01-01

    KAERI (Korea Atomic Energy Research Institute) is developing an accelerator driven system (ADS) named HYPER (HYbrid Power Extraction Reactor) for a transmutation of long-lived nuclear wastes. One of the challenging tasks for the HYPER system is to design a large spallation target having a beam power of 15∼25 MW. The present paper focuses on the thermal-hydraulic performance of the active part of the HYPER target. Computational fluid dynamics (CFD) analysis was performed using a commercial code CFX 5.7.1. Several advanced turbulence models with different grid structures were applied. The CFX results show the significant impact of the turbulence model on the window temperature. It is concluded that experimental verifications are very important for the design of the HYPER target. (authors)

  15. Accurate Analysis of Target Characteristic in Bistatic SAR Images: A Dihedral Corner Reflectors Case.

    Science.gov (United States)

    Ao, Dongyang; Li, Yuanhao; Hu, Cheng; Tian, Weiming

    2017-12-22

    The dihedral corner reflectors are the basic geometric structure of many targets and are the main contributions of radar cross section (RCS) in the synthetic aperture radar (SAR) images. In stealth technologies, the elaborate design of the dihedral corners with different opening angles is a useful approach to reduce the high RCS generated by multiple reflections. As bistatic synthetic aperture sensors have flexible geometric configurations and are sensitive to the dihedral corners with different opening angles, they specially fit for the stealth target detections. In this paper, the scattering characteristic of dihedral corner reflectors is accurately analyzed in bistatic synthetic aperture images. The variation of RCS with the changing opening angle is formulated and the method to design a proper bistatic radar for maximizing the detection capability is provided. Both the results of the theoretical analysis and the experiments show the bistatic SAR could detect the dihedral corners, under a certain bistatic angle which is related to the geometry of target structures.

  16. Detection of Moving Targets Based on Doppler Spectrum Analysis Technique for Passive Coherent Radar

    Directory of Open Access Journals (Sweden)

    Zhao Yao-dong

    2013-06-01

    Full Text Available A novel method of moving targets detection taking Doppler spectrum analysis technique for Passive Coherent Radar (PCR is provided. After dividing the receiving signals into segments as pulse series, it utilizes the technique of pulse compress and Doppler processing to detect and locate the targets. Based on the algorithm for Pulse-Doppler (PD radar, the equipollence between continuous and pulsed wave in match filtering is proved and details of this method are introduced. To compare it with the traditional method of Cross-Ambiguity Function (CAF calculation, the relationship and mathematical modes of them are analyzed, with some suggestions on parameters choosing. With little influence to the gain of targets, the method can greatly promote the processing efficiency. The validity of the proposed method is demonstrated by offline processing real collected data sets and simulation results.

  17. Deterministic and stochastic analysis of alternative climate targets under differentiated cooperation regimes

    International Nuclear Information System (INIS)

    Loulou, Richard; Labriet, Maryse; Kanudia, Amit

    2009-01-01

    This article analyzes the feasibility of attaining a variety of climate targets during the 21st century, under alternative cooperation regimes by groups of countries. Five climate targets of increasing severity are analyzed, following the EMF-22 experiment. Each target is attempted under two cooperation regimes, a First Best scenario where all countries fully cooperate from 2012 on, and a Second Best scenario where the World is partitioned into three groups, and each group of countries enters the cooperation at a different date, and implement emission abatement actions in a progressive manner, once in the coalition. The resulting ten combinations are simulated via the ETSAP-TIAM technology based, integrated assessment model. In addition to the 10 separate case analyses, the article proposes a probabilistic treatment of three targets under the First Best scenario, and shows that the three forcing targets may in fact be interpreted as a single target on global temperature change, while assuming that the climate sensitivity C s is uncertain. It is shown that such an interpretation is possible only if the probability distribution of C s is carefully chosen. The analysis of the results shows that the lowest forcing level is unattainable unless immediate coordinated action is undertaken by all countries, and even so only at a high global cost. The middle and the high forcing levels are feasible at affordable global costs, even under the Second Best scenario. Another original contribution of this article is to explain why certain combinations of technological choices are made by the model, and in particular why the climate target clearly supersedes the usually accepted objective of improving energy efficiency. The analysis shows that under some climate targets, it is not optimal to improve energy efficiency, but rather to take advantage of certain technologies that help to reach the climate objective, but that happen to be less energy efficient than even the technologies

  18. Buffer AVL Alone Does Not Inactivate Ebola Virus in a Representative Clinical Sample Type.

    Science.gov (United States)

    Smither, Sophie J; Weller, Simon A; Phelps, Amanda; Eastaugh, Lin; Ngugi, Sarah; O'Brien, Lyn M; Steward, Jackie; Lonsdale, Steve G; Lever, Mark S

    2015-10-01

    Rapid inactivation of Ebola virus (EBOV) is crucial for high-throughput testing of clinical samples in low-resource, outbreak scenarios. The EBOV inactivation efficacy of Buffer AVL (Qiagen) was tested against marmoset serum (EBOV concentration of 1 × 10(8) 50% tissue culture infective dose per milliliter [TCID50 · ml(-1)]) and murine blood (EBOV concentration of 1 × 10(7) TCID50 · ml(-1)) at 4:1 vol/vol buffer/sample ratios. Posttreatment cell culture and enzyme-linked immunosorbent assay (ELISA) analysis indicated that treatment with Buffer AVL did not inactivate EBOV in 67% of samples, indicating that Buffer AVL, which is designed for RNA extraction and not virus inactivation, cannot be guaranteed to inactivate EBOV in diagnostic samples. Murine blood samples treated with ethanol (4:1 [vol/vol] ethanol/sample) or heat (60°C for 15 min) also showed no viral inactivation in 67% or 100% of samples, respectively. However, combined Buffer AVL and ethanol or Buffer AVL and heat treatments showed total viral inactivation in 100% of samples tested. The Buffer AVL plus ethanol and Buffer AVL plus heat treatments were also shown not to affect the extraction of PCR quality RNA from EBOV-spiked murine blood samples. © Crown copyright 2015.

  19. Seismic analysis of fuel and target assemblies at a production reactor

    International Nuclear Information System (INIS)

    Braverman, J.I.; Wang, Y.K.

    1991-01-01

    This paper describes the unique modeling and analysis considerations used to assess the seismic adequacy of the fuel and target assemblies in a production reactor at Savannah River Site. This confirmatory analysis was necessary to provide assurance that the reactor can operate safely during a seismic event and be brought to a safe shutdown condition. The plant which was originally designed in the 1950's required to be assessed to more current seismic criteria. The design of the reactor internals and the magnitude of the structural responses enabled the use of a linear elastic dynamic analysis. A seismic analysis was performed using a finite element model consisting of the fuel and target assemblies, reactor tank, and a portion of the concrete structure supporting the reactor tank. The effects of submergence of the fuel and target assemblies in the water contained within the reactor tank can have a significant effect on their seismic response. Thus, the model included hydrodynamic fluid coupling effects between the assemblies and the reactor tank. Fluid coupling mass terms were based on formulations for solid bodies immersed in incompressible and frictionless fluids. The potential effects of gap conditions were also assessed in this evaluation. 5 refs., 6 figs., 1 tab

  20. Key tumor suppressor genes inactivated by "greater promoter" methylation and somatic mutations in head and neck cancer

    NARCIS (Netherlands)

    Guerrero-Preston, Rafael; Michailidi, Christina; Marchionni, Luigi; Pickering, Curtis R.; Frederick, Mitchell J.; Myers, Jeffrey N.; Yegnasubramanian, Srinivasan; Hadar, Tal; Noordhuis, Maartje G.; Zizkova, Veronika; Fertig, Elana; Agrawal, Nishant; Westra, William; Koch, Wayne; Califano, Joseph; Velculescu, Victor E.; Sidransky, David

    Tumor suppressor genes (TSGs) are commonly inactivated by somatic mutation and/or promoter methylation; yet, recent high-throughput genomic studies have not identified key TSGs inactivated by both mechanisms. We pursued an integrated molecular analysis based on methylation binding domain sequencing

  1. Skewed X-inactivation in cloned mice

    International Nuclear Information System (INIS)

    Senda, Sho; Wakayama, Teruhiko; Yamazaki, Yukiko; Ohgane, Jun; Hattori, Naka; Tanaka, Satoshi; Yanagimachi, Ryuzo; Shiota, Kunio

    2004-01-01

    In female mammals, dosage compensation for X-linked genes is accomplished by inactivation of one of two X chromosomes. The X-inactivation ratio (a percentage of the cells with inactivated maternal X chromosomes in the whole cells) is skewed as a consequence of various genetic mutations, and has been observed in a number of X-linked disorders. We previously reported that phenotypically normal full-term cloned mouse fetuses had loci with inappropriate DNA methylation. Thus, cloned mice are excellent models to study abnormal epigenetic events in mammalian development. In the present study, we analyzed X-inactivation ratios in adult female cloned mice (B6C3F1). Kidneys of eight naturally produced controls and 11 cloned mice were analyzed. Although variations in X-inactivation ratio among the mice were observed in both groups, the distributions were significantly different (Ansary-Bradley test, P < 0.01). In particular, 2 of 11 cloned mice showed skewed X-inactivation ratios (19.2% and 86.8%). Similarly, in intestine, 1 of 10 cloned mice had a skewed ratio (75.7%). Skewed X-inactivation was observed to various degrees in different tissues of different individuals, suggesting that skewed X-inactivation in cloned mice is the result of secondary cell selection in combination with stochastic distortion of primary choice. The present study is the first demonstration that skewed X-inactivation occurs in cloned animals. This finding is important for understanding both nuclear transfer technology and etiology of X-linked disorders

  2. A BRDF-BPDF database for the analysis of Earth target reflectances

    Science.gov (United States)

    Breon, Francois-Marie; Maignan, Fabienne

    2017-01-01

    Land surface reflectance is not isotropic. It varies with the observation geometry that is defined by the sun, view zenith angles, and the relative azimuth. In addition, the reflectance is linearly polarized. The reflectance anisotropy is quantified by the bidirectional reflectance distribution function (BRDF), while its polarization properties are defined by the bidirectional polarization distribution function (BPDF). The POLDER radiometer that flew onboard the PARASOL microsatellite remains the only space instrument that measured numerous samples of the BRDF and BPDF of Earth targets. Here, we describe a database of representative BRDFs and BPDFs derived from the POLDER measurements. From the huge number of data acquired by the spaceborne instrument over a period of 7 years, we selected a set of targets with high-quality observations. The selection aimed for a large number of observations, free of significant cloud or aerosol contamination, acquired in diverse observation geometries with a focus on the backscatter direction that shows the specific hot spot signature. The targets are sorted according to the 16-class International Geosphere-Biosphere Programme (IGBP) land cover classification system, and the target selection aims at a spatial representativeness within the class. The database thus provides a set of high-quality BRDF and BPDF samples that can be used to assess the typical variability of natural surface reflectances or to evaluate models. It is available freely from the PANGAEA website (PANGAEA.864090" target="_blank">doi:10.1594/PANGAEA.864090). In addition to the database, we provide a visualization and analysis tool based on the Interactive Data Language (IDL). It allows an interactive analysis of the measurements and a comparison against various BRDF and BPDF analytical models. The present paper describes the input data, the selection principles, the database format, and the analysis tool

  3. Towards understanding the lifespan extension by reduced insulin signaling: bioinformatics analysis of DAF-16/FOXO direct targets in Caenorhabditis elegans.

    Science.gov (United States)

    Li, Yan-Hui; Zhang, Gai-Gai

    2016-04-12

    DAF-16, the C. elegans FOXO transcription factor, is an important determinant in aging and longevity. In this work, we manually curated FOXODB http://lyh.pkmu.cn/foxodb/, a database of FOXO direct targets. It now covers 208 genes. Bioinformatics analysis on 109 DAF-16 direct targets in C. elegans found interesting results. (i) DAF-16 and transcription factor PQM-1 co-regulate some targets. (ii) Seventeen targets directly regulate lifespan. (iii) Four targets are involved in lifespan extension induced by dietary restriction. And (iv) DAF-16 direct targets might play global roles in lifespan regulation.

  4. Analysis of the thermomechanical behavior of the IFMIF bayonet target assembly under design loading scenarios

    Energy Technology Data Exchange (ETDEWEB)

    Bernardi, D., E-mail: davide.bernardi@enea.it [ENEA Brasimone, Camugnano, BO (Italy); Arena, P.; Bongiovì, G.; Di Maio, P.A. [Dipartimento di Energia, Ingegneria dell’Informazione e Modelli Matematici, Università di Palermo, Viale delle Scienze, Palermo (Italy); Frisoni, M. [ENEA Bologna, Via Martiri di Monte Sole 4, Bologna (Italy); Miccichè, G.; Serra, M. [ENEA Brasimone, Camugnano, BO (Italy)

    2015-10-15

    In the framework of the IFMIF Engineering Validation and Engineering Design Activities (IFMIF/EVEDA) phase, ENEA is responsible for the design of the European concept of the IFMIF lithium target system which foresees the possibility to periodically replace only the most irradiated and thus critical component (i.e., the backplate) while continuing to operate the rest of the target for a longer period (the so-called bayonet backplate concept). In this work, the results of the steady state thermomechanical analysis of the IFMIF bayonet target assembly under two different design loading scenarios (a “hot” scenario and a “cold” scenario) are briefly reported highlighting the relevant indications obtained with respect to the fulfillment of the design requirements. In particular, the analyses have shown that in the hot scenario the temperatures reached in the target assembly are within the material acceptable limits while in the cold scenario transition below the ductile to brittle transition temperature (DBTT) cannot be excluded. Moreover, results indicate that the contact between backplate and high flux test module is avoided and that the overall structural integrity of the system is assured in both scenarios. However, stress linearization analysis reveals that ITER Structural Design Criteria for In-vessel Components (SDC-IC) design rules are not always met along the selected paths at backplate middle plane section in the hot scenario, thus suggesting the need of a revision of the backplate design or a change of the operating conditions.

  5. Thermal analysis of LEU modified Cintichem target irradiated in TRIGA reactor

    International Nuclear Information System (INIS)

    Catana, A; Toma, C.

    2009-01-01

    Actions conceived during last years at international level for conversion of Molybdenum fabrication process from HEU to LEU targets utilization created opportunities for INR to get access to information and participating to international discussions under IAEA auspices. Concrete steps for developing fission Molybdenum technology were facilitated. Institute of Nuclear Research bringing together a number of conditions like suitable irradiation possibilities, direct communication between reactor and hot cell facility, handling capacity of high radioactive sources, and simultaneously the existence of an expanding internal market, decided to undertake the necessary steps in order to produce fission molybdenum. Over the course of last years of efforts in this direction we developed the steps for fission Molybdenum technology development based on modified Cintichem process in accordance with the Argonne National Laboratory proved methodology. Progress made by INR to heat transfer computations of annular target using is presented. An advanced thermal-hydraulic analysis was performed to estimate the heat removal capability for an enriched uranium (LEU) foil annular target irradiated in TRIGA reactor core. As a result, the present analysis provides an upper limit estimate of the LEU-foil and external target surface temperatures during irradiation in TRIGA 14 MW reactor. (authors)

  6. Effectiveness and economic analysis of the whole cell/recombinant B subunit (WC/rbs inactivated oral cholera vaccine in the prevention of traveller's diarrhoea

    Directory of Open Access Journals (Sweden)

    Diez-Diaz Rosa

    2009-05-01

    Full Text Available Abstract Background Nowadays there is a debate about the indication of the oral whole-cell/recombinant B-subunit cholera vaccine (WC/rBS in traveller's diarrhoea. However, a cost-benefit analysis based on real data has not been published. Methods A cost-effectiveness and cost-benefit study of the oral cholera vaccine (WC/rBS, Dukoral® for the prevention of traveller's diarrhoea (TD was performed in subjects travelling to cholera risk areas. The effectiveness of WC/rBS vaccine in the prevention of TD was analyzed in 362 travellers attending two International Vaccination Centres in Spain between May and September 2005. Results The overall vaccine efficacy against TD was 42,6%. Direct healthcare-related costs as well as indirect costs (lost vacation days subsequent to the disease were considered. Preventive vaccination against TD resulted in a mean saving of 79.26 € per traveller. Conclusion According to the cost-benefit analysis performed, the recommendation for WC/rBS vaccination in subjects travelling to zones at risk of TD is beneficial for the traveller, regardless of trip duration and visited continent.

  7. Allocating the Fixed Resources and Setting Targets in Integer Data Envelopment Analysis

    Directory of Open Access Journals (Sweden)

    Kobra Gholami

    2013-11-01

    Full Text Available Data envelopment analysis (DEA is a non-parametric approach to evaluate a set of decision making units (DMUs consuming multiple inputs to produce multiple outputs. Formally, DEA use to estimate the efficiency score into the empirical efficient frontier. Also, DEA can be used to allocate resources and set targets for future forecast. The data are continuous in the standard DEA model whereas there are many problems in the real life that data must be integer such as number of employee, machinery, expert and so on. Thus in this paper we propose an approach to allocate fixed resources and set fixed targets with selective integer assumption that is based on an integer data envelopment analysis (IDEA approach for the first time. The major aim in this approach is preserving the efficiency score of DMUs. We use the concept of benchmarking to reach this aim. The numerical example gets to illustrate the applicability of the proposed method.

  8. (1S, 3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115), a potent gamma-aminobutyric acid aminotransferase inactivator for the treatment of cocaine addiction

    DEFF Research Database (Denmark)

    Pan, Yue; Gerasimov, Madina R; Kvist, Trine

    2012-01-01

    Vigabatrin, a GABA aminotransferase (GABA-AT) inactivator, is used to treat infantile spasms and refractory complex partial seizures and is in clinical trials to treat addiction. We evaluated a novel GABA-AT inactivator (CPP-115) and observed that it does not exhibit other GABAergic or off-target...

  9. Analysis and Simulation of Multi-target Echo Signals from a Phased Array Radar

    OpenAIRE

    Jia Zhen; Zhou Rui

    2017-01-01

    The construction of digital radar simulation systems has been a research hotspot of the radar field. This paper focuses on theoretical analysis and simulation of multi-target echo signals produced in a phased array radar system, and constructs an array antenna element and a signal generation environment. The antenna element is able to simulate planar arrays and optimizes these arrays by adding window functions. And the signal environment can model and simulate radar transmission signals, rada...

  10. Methodological Approach to Company Cash Flows Target-Oriented Forecasting Based on Financial Position Analysis

    OpenAIRE

    Sergey Krylov

    2012-01-01

    The article treats a new methodological approach to the company cash flows target-oriented forecasting based on its financial position analysis. The approach is featured to be universal and presumes application of the following techniques developed by the author: financial ratio values correction techniques and correcting cash flows techniques. The financial ratio values correction technique assumes to analyze and forecast company financial position while the correcting cash flows technique i...

  11. Targeting khat or targeting Somalis? A discourse analysis of project evaluations on khat abuse among Somali immigrants in Scandinavia

    Directory of Open Access Journals (Sweden)

    Nordgren Johan

    2015-09-01

    Full Text Available BACKGROUND – In Denmark, Norway and Sweden, the use of the psychoactive plant khat is widely seen as a social and health problem exclusively affecting the Somali immigrant population. Several projects by governmental and municipal bodies and agencies have been initiated to reduce khat use and abuse within this target population.

  12. In Silico Affinity Profiling of Neuroactive Polyphenols for Post-Traumatic Calpain Inactivation: A Molecular Docking and Atomistic Simulation Sensitivity Analysis

    Directory of Open Access Journals (Sweden)

    Pradeep Kumar

    2014-12-01

    Full Text Available Calcium-activated nonlysosomal neutral proteases, calpains, are believed to be early mediators of neuronal damage associated with neuron death and axonal degeneration after traumatic neural injuries. In this study, a library of biologically active small molecular weight calpain inhibitors was used for model validation and inhibition site recognition. Subsequently, two natural neuroactive polyphenols, curcumin and quercetin, were tested for their sensitivity and activity towards calpain’s proteolytic sequence and compared with the known calpain inhibitors via detailed molecular mechanics (MM, molecular dynamics (MD, and docking simulations. The MM and MD energy profiles (SJA6017 < AK275 < AK295 < PD151746 < quercetin < leupeptin < PD150606 < curcumin < ALLN < ALLM < MDL-28170 < calpeptin and the docking analysis (AK275 < AK295 < PD151746 < ALLN < PD150606 < curcumin < leupeptin < quercetin < calpeptin < SJA6017 < MDL-28170 < ALLM demonstrated that polyphenols conferred comparable calpain inhibition profiling. The modeling paradigm used in this study provides the first detailed account of corroboration of enzyme inhibition efficacy of calpain inhibitors and the respective calpain–calpain inhibitor molecular complexes’ energetic landscape and in addition stimulates the polyphenol bioactive paradigm for post-SCI intervention with implications reaching to experimental in vitro, in cyto, and in vivo studies.

  13. Meta-analysis of the Effects of Sanitizing Treatments on Salmonella, Escherichia coli O157:H7, and Listeria monocytogenes Inactivation in Fresh Produce

    Science.gov (United States)

    Prado-Silva, Leonardo; Cadavez, Vasco; Gonzales-Barron, Ursula; Rezende, Ana Carolina B.

    2015-01-01

    The aim of this study was to perform a meta-analysis of the effects of sanitizing treatments of fresh produce on Salmonella spp., Escherichia coli O157:H7, and Listeria monocytogenes. From 55 primary studies found to report on such effects, 40 were selected based on specific criteria, leading to more than 1,000 data on mean log reductions of these three bacterial pathogens impairing the safety of fresh produce. Data were partitioned to build three meta-analytical models that could allow the assessment of differences in mean log reductions among pathogens, fresh produce, and sanitizers. Moderating variables assessed in the meta-analytical models included type of fresh produce, type of sanitizer, concentration, and treatment time and temperature. Further, a proposal was done to classify the sanitizers according to bactericidal efficacy by means of a meta-analytical dendrogram. The results indicated that both time and temperature significantly affected the mean log reductions of the sanitizing treatment (P vegetables (for example, 3.04 mean log reductions [2.32 to 3.76] obtained for carrots). Among the pathogens, E. coli O157:H7 was more resistant to ozone (1.6 mean log reductions), while L. monocytogenes and Salmonella presented high resistance to organic acids, such as citric acid, acetic acid, and lactic acid (∼3.0 mean log reductions). With regard to the sanitizers, it has been found that slightly acidic electrolyzed water, acidified sodium chlorite, and the gaseous chlorine dioxide clustered together, indicating that they possessed the strongest bactericidal effect. The results reported seem to be an important achievement for advancing the global understanding of the effectiveness of sanitizers for microbial safety of fresh produce. PMID:26362982

  14. The inactivation of human CYP2E1 by phenethyl isothiocyanate, a naturally occurring chemopreventive agent, and its oxidative bioactivation.

    Science.gov (United States)

    Yoshigae, Yasushi; Sridar, Chitra; Kent, Ute M; Hollenberg, Paul F

    2013-04-01

    Phenethylisothiocyanate (PEITC), a naturally occurring isothiocyanate and potent cancer chemopreventive agent, works by multiple mechanisms, including the inhibition of cytochrome P450 (P450) enzymes, such as CYP2E1, that are involved in the bioactivation of carcinogens. PEITC has been reported to be a mechanism-based inactivator of some P450s. We describe here the possible mechanism for the inactivation of human CYP2E1 by PEITC, as well as the putative intermediate that might be involved in the bioactivation of PEITC. PEITC inactivated recombinant CYP2E1 with a partition ratio of 12, and the inactivation was not inhibited in the presence of glutathione (GSH) and not fully recovered by dialysis. The inactivation of CYP2E1 by PEITC is due to both heme destruction and protein modification, with the latter being the major pathway for inactivation. GSH-adducts of phenethyl isocyanate (PIC) and phenethylamine were detected during the metabolism by CYP2E1, indicating formation of PIC as a reactive intermediate following P450-catalyzed desulfurization of PEITC. Surprisingly, PIC bound covalently to CYP2E1 to form protein adducts but did not inactivate the enzyme. Liquid chromatography mass spectroscopy analysis of the inactivated CYP2E1 apo-protein suggests that a reactive sulfur atom generated during desulfurization of PEITC is involved in the inactivation of CYP2E1. Our data suggest that the metabolism of PEITC by CYP2E1 that results in the inactivation of CYP2E1 may occur by a mechanism similar to that observed with other sulfur-containing compounds, such as parathion. Digestion of the inactivated enzyme and analysis by SEQUEST showed that Cys 268 may be the residue modified by PIC.

  15. Ensemble Sensitivity Analysis of a Severe Downslope Windstorm in Complex Terrain: Implications for Forecast Predictability Scales and Targeted Observing Networks

    Science.gov (United States)

    2013-09-01

    observations, linear regression finds the straight line that explains the linear relationship of the sample. This line is given by the equation y = mx + b...SENSITIVITY ANALYSIS OF A SEVERE DOWNSLOPE WINDSTORM IN COMPLEX TERRAIN: IMPLICATIONS FOR FORECAST PREDICTABILITY SCALES AND TARGETED OBSERVING...SENSITIVITY ANALYSIS OF A SEVERE DOWNSLOPE WINDSTORM IN COMPLEX TERRAIN: IMPLICATIONS FOR FORECAST PREDICTABILITY SCALES AND TARGETED OBSERVING NETWORKS

  16. An analysis of possible off target effects following CAS9/CRISPR targeted deletions of neuropeptide gene enhancers from the mouse genome.

    Science.gov (United States)

    Hay, Elizabeth Anne; Khalaf, Abdulla Razak; Marini, Pietro; Brown, Andrew; Heath, Karyn; Sheppard, Darrin; MacKenzie, Alasdair

    2017-08-01

    We have successfully used comparative genomics to identify putative regulatory elements within the human genome that contribute to the tissue specific expression of neuropeptides such as galanin and receptors such as CB1. However, a previous inability to rapidly delete these elements from the mouse genome has prevented optimal assessment of their function in-vivo. This has been solved using CAS9/CRISPR genome editing technology which uses a bacterial endonuclease called CAS9 that, in combination with specifically designed guide RNA (gRNA) molecules, cuts specific regions of the mouse genome. However, reports of "off target" effects, whereby the CAS9 endonuclease is able to cut sites other than those targeted, limits the appeal of this technology. We used cytoplasmic microinjection of gRNA and CAS9 mRNA into 1-cell mouse embryos to rapidly generate enhancer knockout mouse lines. The current study describes our analysis of the genomes of these enhancer knockout lines to detect possible off-target effects. Bioinformatic analysis was used to identify the most likely putative off-target sites and to design PCR primers that would amplify these sequences from genomic DNA of founder enhancer deletion mouse lines. Amplified DNA was then sequenced and blasted against the mouse genome sequence to detect off-target effects. Using this approach we were unable to detect any evidence of off-target effects in the genomes of three founder lines using any of the four gRNAs used in the analysis. This study suggests that the problem of off-target effects in transgenic mice have been exaggerated and that CAS9/CRISPR represents a highly effective and accurate method of deleting putative neuropeptide gene enhancer sequences from the mouse genome. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Immune checkpoint inhibitors and targeted therapies for metastatic melanoma: A network meta-analysis.

    Science.gov (United States)

    Pasquali, Sandro; Chiarion-Sileni, Vanna; Rossi, Carlo Riccardo; Mocellin, Simone

    2017-03-01

    Immune checkpoint inhibitors and targeted therapies, two new class of drugs for treatment of metastatic melanoma, have not been compared in randomized controlled trials (RCT). We quantitatively summarized the evidence and compared immune and targeted therapies in terms of both efficacy and toxicity. A comprehensive search for RCTs of immune checkpoint inhibitors and targeted therapies was conducted to August 2016. Using a network meta-analysis approach, treatments were compared with each other and ranked based on their effectiveness (as measured by the impact on progression-free survival [PFS]) and acceptability (the inverse of high grade toxicity). Twelve RCTs enrolling 6207 patients were included. Network meta-analysis generated 15 comparisons. Combined BRAF and MEK inhibitors were associated with longer PFS as compared to anti-CTLA4 (HR: 0.22; 95% confidence interval [CI]: 0.12-0.41) and anti-PD1 antibodies alone (HR: 0.38; CI: 0.20-0.72). However, anti-PD1 monoclonal antibodies were less toxic than anti-CTLA4 monoclonal antibodies (RR: 0.65; CI: 0.40-0.78) and their combination significantly increased toxicity compared to either single agent anti-CTLA4 (RR: 2.06; CI: 1.45-2.93) or anti-PD1 monoclonal antibodies (RR: 3.67; CI: 2.27-5.96). Consistently, ranking analysis suggested that the combination of targeted therapies is the most effective strategy, whereas single agent anti-PD1 antibodies have the best acceptability. The GRADE level of evidence quality for these findings was moderate to low. The simultaneous inhibition of BRAF and MEK appears the most effective treatment for melanomas harboring BRAF V600 mutation, although anti-PD1 antibodies appear to be less toxic. Further research is needed to increase the quality of evidence. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Physical inactivation and stabilization of sludges

    International Nuclear Information System (INIS)

    Alexandre, D.

    1979-07-01

    High temperature conditioning of sludge is a stabilization process that insures sterilization. Both thermal pasteurization and irradiation are inactivation processes. Viruses and parasites are inactivated at 70-80 0 C. Total bacterial destruction requires higher temperatures and/or detention time. Radio sensitivity of pathogens and pertinent treatment parameters are examined. If sludge is to be land disposed, disinfection requires irradiation doses ranging 500 Krad; if cattle feeding is considered, the required dose is 1 Mrad

  19. Microbial Inactivation by Ultrasound Assisted Supercritical Fluids

    Science.gov (United States)

    Benedito, Jose; Ortuño, Carmen; Castillo-Zamudio, Rosa Isela; Mulet, Antonio

    A method combining supercritical carbon dioxide (SC-CO2) and high power ultrasound (HPU) has been developed and tested for microbial/enzyme inactivation purposes, at different process conditions for both liquid and solid matrices. In culture media, using only SC-CO2, the inactivation rate of E. coli and S. cerevisiae increased with pressure and temperature; and the total inactivation (7-8 log-cycles) was attained after 25 and 140 min of SC-CO2 (350 bar, 36 °C) treatment, respectively. Using SC-CO2+HPU, the time for the total inactivation of both microorganisms was reduced to only 1-2 min, at any condition selected. The SC-CO2+HPU inactivation of both microorganisms was slower in juices (avg. 4.9 min) than in culture media (avg. 1.5 min). In solid samples (chicken, turkey ham and dry-cured pork cured ham) treated with SC-CO2 and SC-CO2+HPU, the inactivation rate of E. coli increased with temperature. The application of HPU to the SC-CO2 treatments accelerated the inactivation rate of E. coli and that effect was more pronounced in treatments with isotonic solution surrounding the solid food samples. The application of HPU enhanced the SC-CO2 inactivation mechanisms of microorganisms, generating a vigorous agitation that facilitated the CO2 solubilization and the mass transfer process. The cavitation generated by HPU could damage the cell walls accelerating the extraction of vital constituents and the microbial death. Thus, using the combined technique, reasonable industrial processing times and mild process conditions could be used which could result into a cost reduction and lead to the minimization in the food nutritional and organoleptic changes.

  20. Critical analysis of the potential for therapeutic targeting of mammalian target of rapamycin (mTOR in gastric cancer

    Directory of Open Access Journals (Sweden)

    Inokuchi M

    2014-04-01

    Full Text Available Mikito Inokuchi,1 Keiji Kato,1 Kazuyuki Kojima,2 Kenichi Sugihara1 1Department of Surgical Oncology, 2Department of Minimally Invasive Surgery, Tokyo Medical and Dental University, Tokyo, Japan Abstract: Multidisciplinary treatment including chemotherapy has become the global standard of care for patients with metastatic gastric cancer (mGC; nonetheless, survival remains poor. Although many molecular-targeted therapies have been developed for various cancers, only anti-HER2 treatment has produced promising results in patients with mGC. Mammalian target of rapamycin (mTOR plays a key role in cell proliferation, antiapoptosis, and metastasis in signaling pathways from the tyrosine kinase receptor, and its activation has been demonstrated in gastric cancer (GC cells. This review discusses the clinical relevance of mTOR in GC and examines its potential as a therapeutic target in patients with mGC. Preclinical studies in animal models suggest that suppression of the mTOR pathway inhibits the proliferation of GC cells and delays tumor progression. The mTOR inhibitor everolimus has been evaluated as second- or third-line treatment in clinical trials. Adverse events were well tolerated although the effectiveness of everolimus alone was limited. Everolimus is now being evaluated in combination with chemotherapy in Phase III clinical studies in this subgroup of patients. Two Phase III studies include exploratory biomarker research designed to evaluate the predictive value of the expression or mutation of molecules related to the Akt/mTOR signaling pathway. These biomarker studies may lead to the realization of targeted therapy for selected patients with mGC in the future. Keywords: gastric cancer, mTOR, everolimus

  1. In-silico Metabolome Target Analysis Towards PanC-based Antimycobacterial Agent Discovery.

    Science.gov (United States)

    Khoshkholgh-Sima, Baharak; Sardari, Soroush; Izadi Mobarakeh, Jalal; Khavari-Nejad, Ramezan Ali

    2015-01-01

    Mycobacterium tuberculosis, the main cause of tuberculosis (TB), has still remained a global health crisis especially in developing countries. Tuberculosis treatment is a laborious and lengthy process with high risk of noncompliance, cytotoxicity adverse events and drug resistance in patient. Recently, there has been an alarming rise of drug resistant in TB. In this regard, it is an unmet need to develop novel antitubercular medicines that target new or more effective biochemical pathways to prevent drug resistant Mycobacterium. Integrated study of metabolic pathways through in-silico approach played a key role in antimycobacterial design process in this study. Our results suggest that pantothenate synthetase (PanC), anthranilate phosphoribosyl transferase (TrpD) and 3-isopropylmalate dehydratase (LeuD) might be appropriate drug targets. In the next step, in-silico ligand analysis was used for more detailed study of chemical tractability of targets. This was helpful to identify pantothenate synthetase (PanC, Rv3602c) as the best target for antimycobacterial design procedure. Virtual library screening on the best ligand of PanC was then performed for inhibitory ligand design. At the end, five chemical intermediates showed significant inhibition of Mycobacterium bovis with good selectivity indices (SI) ≥10 according to Tuberculosis Antimicrobial Acquisition & Coordinating Facility of US criteria for antimycobacterial screening programs.

  2. Identification of Cell Surface Targets through Meta-analysis of Microarray Data

    Directory of Open Access Journals (Sweden)

    Henry Haeberle

    2012-07-01

    Full Text Available High-resolution image guidance for resection of residual tumor cells would enable more precise and complete excision for more effective treatment of cancers, such as medulloblastoma, the most common pediatric brain cancer. Numerous studies have shown that brain tumor patient outcomes correlate with the precision of resection. To enable guided resection with molecular specificity and cellular resolution, molecular probes that effectively delineate brain tumor boundaries are essential. Therefore, we developed a bioinformatics approach to analyze micro-array datasets for the identification of transcripts that encode candidate cell surface biomarkers that are highly enriched in medulloblastoma. The results identified 380 genes with greater than a two-fold increase in the expression in the medulloblastoma compared with that in the normal cerebellum. To enrich for targets with accessibility for extracellular molecular probes, we further refined this list by filtering it with gene ontology to identify genes with protein localization on, or within, the plasma membrane. To validate this meta-analysis, the top 10 candidates were evaluated with immunohistochemistry. We identified two targets, fibrillin 2 and EphA3, which specifically stain medulloblastoma. These results demonstrate a novel bioinformatics approach that successfully identified cell surface and extracellular candidate markers enriched in medulloblastoma versus adjacent cerebellum. These two proteins are high-value targets for the development of tumor-specific probes in medulloblastoma. This bioinformatics method has broad utility for the identification of accessible molecular targets in a variety of cancers and will enable probe development for guided resection.

  3. Analysis on Target Detection and Classification in LTE Based Passive Forward Scattering Radar

    Directory of Open Access Journals (Sweden)

    Raja Syamsul Azmir Raja Abdullah

    2016-09-01

    Full Text Available The passive bistatic radar (PBR system can utilize the illuminator of opportunity to enhance radar capability. By utilizing the forward scattering technique and procedure into the specific mode of PBR can provide an improvement in target detection and classification. The system is known as passive Forward Scattering Radar (FSR. The passive FSR system can exploit the peculiar advantage of the enhancement in forward scatter radar cross section (FSRCS for target detection. Thus, the aim of this paper is to show the feasibility of passive FSR for moving target detection and classification by experimental analysis and results. The signal source is coming from the latest technology of 4G Long-Term Evolution (LTE base station. A detailed explanation on the passive FSR receiver circuit, the detection scheme and the classification algorithm are given. In addition, the proposed passive FSR circuit employs the self-mixing technique at the receiver; hence the synchronization signal from the transmitter is not required. The experimental results confirm the passive FSR system’s capability for ground target detection and classification. Furthermore, this paper illustrates the first classification result in the passive FSR system. The great potential in the passive FSR system provides a new research area in passive radar that can be used for diverse remote monitoring applications.

  4. Analysis on Target Detection and Classification in LTE Based Passive Forward Scattering Radar.

    Science.gov (United States)

    Raja Abdullah, Raja Syamsul Azmir; Abdul Aziz, Noor Hafizah; Abdul Rashid, Nur Emileen; Ahmad Salah, Asem; Hashim, Fazirulhisyam

    2016-09-29

    The passive bistatic radar (PBR) system can utilize the illuminator of opportunity to enhance radar capability. By utilizing the forward scattering technique and procedure into the specific mode of PBR can provide an improvement in target detection and classification. The system is known as passive Forward Scattering Radar (FSR). The passive FSR system can exploit the peculiar advantage of the enhancement in forward scatter radar cross section (FSRCS) for target detection. Thus, the aim of this paper is to show the feasibility of passive FSR for moving target detection and classification by experimental analysis and results. The signal source is coming from the latest technology of 4G Long-Term Evolution (LTE) base station. A detailed explanation on the passive FSR receiver circuit, the detection scheme and the classification algorithm are given. In addition, the proposed passive FSR circuit employs the self-mixing technique at the receiver; hence the synchronization signal from the transmitter is not required. The experimental results confirm the passive FSR system's capability for ground target detection and classification. Furthermore, this paper illustrates the first classification result in the passive FSR system. The great potential in the passive FSR system provides a new research area in passive radar that can be used for diverse remote monitoring applications.

  5. Expression analysis of miRNA and target mRNAs in esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Meng, X.R. [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China); Lu, P. [Gastrointestinal Surgery Department, People' s Hospital of Zhengzhou, Zhengzhou (China); Mei, J.Z.; Liu, G.J. [Medical Oncology Department, People' s Hospital of Zhengzhou, Zhengzhou (China); Fan, Q.X. [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China)

    2014-08-01

    We aimed to investigate miRNAs and related mRNAs through a network-based approach in order to learn the crucial role that they play in the biological processes of esophageal cancer. Esophageal squamous-cell carcinoma (ESCC) and adenocarcinoma (EAC)-related miRNA and gene expression data were downloaded from the Gene Expression Omnibus database, and differentially expressed miRNAs and genes were selected. Target genes of differentially expressed miRNAs were predicted and their regulatory networks were constructed. Differentially expressed miRNA analysis selected four miRNAs associated with EAC and ESCC, among which hsa-miR-21 and hsa-miR-202 were shared by both diseases. hsa-miR-202 was reported for the first time to be associated with esophageal cancer in the present study. Differentially expressed miRNA target genes were mainly involved in cancer-related and signal-transduction pathways. Functional categories of these target genes were related to transcriptional regulation. The results may indicate potential target miRNAs and genes for future investigations of esophageal cancer.

  6. Analysis and Visualization Tool for Targeted Amplicon Bisulfite Sequencing on Ion Torrent Sequencers.

    Directory of Open Access Journals (Sweden)

    Stephan Pabinger

    Full Text Available Targeted sequencing of PCR amplicons generated from bisulfite deaminated DNA is a flexible, cost-effective way to study methylation of a sample at single CpG resolution and perform subsequent multi-target, multi-sample comparisons. Currently, no platform specific protocol, support, or analysis solution is provided to perform targeted bisulfite sequencing on a Personal Genome Machine (PGM. Here, we present a novel tool, called TABSAT, for analyzing targeted bisulfite sequencing data generated on Ion Torrent sequencers. The workflow starts with raw sequencing data, performs quality assessment, and uses a tailored version of Bismark to map the reads to a reference genome. The pipeline visualizes results as lollipop plots and is able to deduce specific methylation-patterns present in a sample. The obtained profiles are then summarized and compared between samples. In order to assess the performance of the targeted bisulfite sequencing workflow, 48 samples were used to generate 53 different Bisulfite-Sequencing PCR amplicons from each sample, resulting in 2,544 amplicon targets. We obtained a mean coverage of 282X using 1,196,822 aligned reads. Next, we compared the sequencing results of these targets to the methylation level of the corresponding sites on an Illumina 450k methylation chip. The calculated average Pearson correlation coefficient of 0.91 confirms the sequencing results with one of the industry-leading CpG methylation platforms and shows that targeted amplicon bisulfite sequencing provides an accurate and cost-efficient method for DNA methylation studies, e.g., to provide platform-independent confirmation of Illumina Infinium 450k methylation data. TABSAT offers a novel way to analyze data generated by Ion Torrent instruments and can also be used with data from the Illumina MiSeq platform. It can be easily accessed via the Platomics platform, which offers a web-based graphical user interface along with sample and parameter storage

  7. Wastewater disinfection by peracetic acid: assessment of models for tracking residual measurements and inactivation.

    Science.gov (United States)

    Santoro, Domenico; Gehr, Ronald; Bartrand, Timothy A; Liberti, Lorenzo; Notarnicola, Michele; Dell'Erba, Adele; Falsanisi, Dario; Haas, Charles N

    2007-07-01

    With its potential for low (if any) disinfection byproduct formation and easy retrofit for chlorine contactors, peracetic acid (PAA) or use of PAA in combination with other disinfectant technologies may be an attractive alternative to chlorine-based disinfection. Examples of systems that might benefit from use of PAA are water reuse schemes or plants discharging to sensitive receiving water bodies. Though PAA is in use in numerous wastewater treatment plants in Europe, its chemical kinetics, microbial inactivation rates, and mode of action against microorganisms are not thoroughly understood. This paper presents results from experimental studies of PAA demand, PAA decay, and microbial inactivation, with a complementary modeling analysis. Model results are used to evaluate techniques for measurement of PAA concentration and to develop hypotheses regarding the mode of action of PAA in bacterial inactivation. Kinetic and microbial inactivation rate data were collected for typical wastewaters and may be useful for engineers in evaluating whether to convert from chlorine to PAA disinfection.

  8. Mycobacteria inactivation using Engineered Water Nanostructures (EWNS).

    Science.gov (United States)

    Pyrgiotakis, Georgios; McDevitt, James; Gao, Ya; Branco, Alan; Eleftheriadou, Mary; Lemos, Bernardo; Nardell, Edward; Demokritou, Philip

    2014-08-01

    Airborne transmitted pathogens such as Mycobacterium tuberculosis (Mtb) cause serious, often fatal infectious disease with enormous global health implications. Due to their unique cell wall and slow growth, mycobacteria are among the most resilient microbial forms. Herein we evaluate the ability of an emerging, chemical-free, nanotechnology-based method to inactivate M. parafortuitum (Mtb surrogate). This method is based on the transformation of atmospheric water vapor into engineered water nano-structures (EWNS) via electrospray. We demonstrate that the EWNS can interact with and inactivate airborne mycobacteria, reducing their concentration levels significantly. Additionally, EWNS can inactivate M. parafortuitum on surfaces eight times faster than the control. The mechanism of mycobacteria inactivation was also investigated in this study. It was demonstrated that the EWNS effectively deliver the reactive oxygen species, encapsulated during the electrospray process, to the bacteria oxidizing their cell membrane resulting into inactivation. Overall, this is a method with the potential to become an effective intervention technology in the battle against airborne infections. This study demonstrates the feasibility of mycobacterium inactivation in airborne form or on contact surfaces using electrospray activated water nano-structures. Given that the method is free of toxic chemicals, this might become an important tool in the prevention of mycobacterial infections, which are notoriously hard to treat. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Cell inactivation by heavy charged particles

    Energy Technology Data Exchange (ETDEWEB)

    Blakely, E A [Lawrence Berkeley Lab., CA (United States). Cell and Molecular Biology Div.

    1992-06-01

    The inactivation of cells resulting in lethal or aberrant effects by charged particles is of growing interest. Charged particles at extremely high LET are capable of completely eliminating cell-type and cell-line differences in repair capacity. It is still not clear however whether the repair systems are inactivated, or merely that heavy-ion lesions are less repairable. Studies correlating the particle inactivation dose of radioresistant cells with intact DNA analyzed with pulse field gel electrophoresis and other techniques may be useful, but more experiments are also needed to assess the fidelity of repair. For particle irradiations between 40-100 keV/{mu}m there is however evidence for particle-induced activation of specific genes in mammalian cells, and certain repair processes in bacteria. New data are available on the inactivation of developmental processes in several systems including seeds, and cells of the nematode C. elegans. Future experimental and theoretical modeling research emphasis should focus on exploring particle-induced inactivation of endpoints assessing functionality and not just lethality, and on analyzing molecular damage and genetic effects arising in damage but non-inactivated survivors. The discrete nature of selective types of particle damage as a function of radiation quality indicates the value of accelerated ions as probes of normal and aberrant biological processes. Information obtained from molecular analyses of damage and repair must however be integrated into the context of cellular and tissue functions of the organism. (orig.).

  10. A novel graphical technique for Pinch Analysis applications: Energy Targets and grassroots design

    International Nuclear Information System (INIS)

    Gadalla, Mamdouh A.

    2015-01-01

    Graphical abstract: A new HEN graphical design. - Highlights: • A new graphical technique for heat exchanger networks design. • Pinch Analysis principles and design rules are better interpreted. • Graphical guidelines for optimum heat integration. • New temperature-based graphs provide user-interactive features. - Abstract: Pinch Analysis is for decades a leading tool to energy integration for retrofit and design. This paper presents a new graphical technique, based on Pinch Analysis, for the grassroots design of heat exchanger networks. In the new graph, the temperatures of hot streams are plotted versus those of the cold streams. The temperature–temperature based graph is constructed to include temperatures of hot and cold streams as straight lines, horizontal lines for hot streams, and vertical lines for cold streams. The graph is applied to determine the pinch temperatures and Energy Targets. It is then used to synthesise graphically a complete exchanger network, achieving the Energy Targets. Within the new graph, exchangers are represented by inclined straight lines, whose slopes are proportional to the ratio of heat capacities and flows. Pinch Analysis principles for design are easily interpreted using this new graphical technique to design a complete exchanger network. Network designs achieved by the new technique can guarantee maximum heat recovery. The new technique can also be employed to simulate basic designs of heat exchanger networks. The strengths of the new tool are that it is simply applied using computers, requires no commercial software, and can be used for academic purposes/engineering education

  11. Membrane permeabilization in relation to inactivation kinetics of Lactobacillus species due to pulsed electric fields.

    Science.gov (United States)

    Wouters, P C; Bos, A P; Ueckert, J

    2001-07-01

    Membrane permeabilization due to pulsed electric field (PEF) treatment of gram-positive Lactobacillus cells was investigated by using propidium iodide uptake and single-cell analysis with flow cytometry. Electric field strength, energy input, treatment time, and growth phase affected membrane permeabilization of Lactobacillus plantarum during PEF treatment. A correlation between PEF inactivation and membrane permeabilization of L. plantarum cells was demonstrated, whereas no relationship was observed between membrane permeabilization and heat inactivation. The same results were obtained with a Lactobacillus fermentum strain, but the latter organism was more PEF resistant and exhibited less membrane permeabilization, indicating that various bacteria have different responses to PEF treatment. While membrane permeabilization was the main factor involved in the mechanism of inactivation, the growth phase and the acidity of the environment also influenced inactivation. By using flow cytometry it was possible to sort cells in the L. plantarum population based on different cell sizes and shapes, and the results were confirmed by image analysis. An apparent effect of morphology on membrane permeabilization was observed, and larger cells were more easily permeabilized than smaller cells. In conclusion, our results indicate that the ability of PEF treatment to cause membrane permeabilization is an important factor in determining inactivation. This finding should have an effect on the final choice of the processing parameters used so that all microorganisms can be inactivated and, consequently, on the use of PEF treatment as an alternative method for preserving food products.

  12. Membrane Permeabilization in Relation to Inactivation Kinetics of Lactobacillus Species due to Pulsed Electric Fields

    Science.gov (United States)

    Wouters, Patrick C.; Bos, Ad P.; Ueckert, Joerg

    2001-01-01

    Membrane permeabilization due to pulsed electric field (PEF) treatment of gram-positive Lactobacillus cells was investigated by using propidium iodide uptake and single-cell analysis with flow cytometry. Electric field strength, energy input, treatment time, and growth phase affected membrane permeabilization of Lactobacillus plantarum during PEF treatment. A correlation between PEF inactivation and membrane permeabilization of L. plantarum cells was demonstrated, whereas no relationship was observed between membrane permeabilization and heat inactivation. The same results were obtained with a Lactobacillus fermentum strain, but the latter organism was more PEF resistant and exhibited less membrane permeabilization, indicating that various bacteria have different responses to PEF treatment. While membrane permeabilization was the main factor involved in the mechanism of inactivation, the growth phase and the acidity of the environment also influenced inactivation. By using flow cytometry it was possible to sort cells in the L. plantarum population based on different cell sizes and shapes, and the results were confirmed by image analysis. An apparent effect of morphology on membrane permeabilization was observed, and larger cells were more easily permeabilized than smaller cells. In conclusion, our results indicate that the ability of PEF treatment to cause membrane permeabilization is an important factor in determining inactivation. This finding should have an effect on the final choice of the processing parameters used so that all microorganisms can be inactivated and, consequently, on the use of PEF treatment as an alternative method for preserving food products. PMID:11425727

  13. Mechanism of microRNA-target interaction: molecular dynamics simulations and thermodynamics analysis.

    Directory of Open Access Journals (Sweden)

    Yonghua Wang

    Full Text Available MicroRNAs (miRNAs are endogenously produced approximately 21-nt riboregulators that associate with Argonaute (Ago proteins to direct mRNA cleavage or repress the translation of complementary RNAs. Capturing the molecular mechanisms of miRNA interacting with its target will not only reinforce the understanding of underlying RNA interference but also fuel the design of more effective small-interfering RNA strands. To address this, in the present work the RNA-bound (Ago-miRNA, Ago-miRNA-target and RNA-free Ago forms were analyzed by performing both molecular dynamics simulations and thermodynamic analysis. Based on the principal component analysis results of the simulation trajectories as well as the correlation analysis in fluctuations of residues, we discover that: 1 three important (PAZ, Mid and PIWI domains exist in Argonaute which define the global dynamics of the protein; 2 the interdomain correlated movements are so crucial for the interaction of Ago-RNAs that they not only facilitate the relaxation of the interactions between residues surrounding the RNA binding channel but also induce certain conformational changes; and 3 it is just these conformational changes that expand the cavity of the active site and open putative pathways for both the substrate uptake and product release. In addition, by thermodynamic analysis we also discover that for both the guide RNA 5'-end recognition and the facilitated site-specific cleavage of the target, the presence of two metal ions (of Mg(2+ plays a predominant role, and this conclusion is consistent with the observed enzyme catalytic cleavage activity in the ternary complex (Ago-miRNA-mRNA. Our results find that it is the set of arginine amino acids concentrated in the nucleotide-binding channel in Ago, instead of the conventionally-deemed seed base-paring, that makes greater contributions in stabilizing the binding of the nucleic acids to Ago.

  14. Mechanism of microRNA-target interaction: molecular dynamics simulations and thermodynamics analysis.

    Science.gov (United States)

    Wang, Yonghua; Li, Yan; Ma, Zhi; Yang, Wei; Ai, Chunzhi

    2010-07-29

    MicroRNAs (miRNAs) are endogenously produced approximately 21-nt riboregulators that associate with Argonaute (Ago) proteins to direct mRNA cleavage or repress the translation of complementary RNAs. Capturing the molecular mechanisms of miRNA interacting with its target will not only reinforce the understanding of underlying RNA interference but also fuel the design of more effective small-interfering RNA strands. To address this, in the present work the RNA-bound (Ago-miRNA, Ago-miRNA-target) and RNA-free Ago forms were analyzed by performing both molecular dynamics simulations and thermodynamic analysis. Based on the principal component analysis results of the simulation trajectories as well as the correlation analysis in fluctuations of residues, we discover that: 1) three important (PAZ, Mid and PIWI) domains exist in Argonaute which define the global dynamics of the protein; 2) the interdomain correlated movements are so crucial for the interaction of Ago-RNAs that they not only facilitate the relaxation of the interactions between residues surrounding the RNA binding channel but also induce certain conformational changes; and 3) it is just these conformational changes that expand the cavity of the active site and open putative pathways for both the substrate uptake and product release. In addition, by thermodynamic analysis we also discover that for both the guide RNA 5'-end recognition and the facilitated site-specific cleavage of the target, the presence of two metal ions (of Mg(2+)) plays a predominant role, and this conclusion is consistent with the observed enzyme catalytic cleavage activity in the ternary complex (Ago-miRNA-mRNA). Our results find that it is the set of arginine amino acids concentrated in the nucleotide-binding channel in Ago, instead of the conventionally-deemed seed base-paring, that makes greater contributions in stabilizing the binding of the nucleic acids to Ago.

  15. Void analysis of target residues at SPS energy -evidence of correlation with fractal behaviour

    International Nuclear Information System (INIS)

    Ghosh, Dipak; Deb, Argha; Das, Rupa . E-mail : dipakghosh_in@yahoo.com

    2007-01-01

    This paper presents an analysis of the target residues in 32 S -AgBr and 16 0 -AgBr interactions at 200 AGeV and 60AGeV respectively in terms of fractal moment by Takagi method and void probability scaling. The study reveals an interesting feature of the production process. In 16 O- AgBr interactions multifractal behaviour is present in both hemispheres and void probability does not show a scaling behaviour, but at high energy the situation changes. In 32 S -AgBr interactions for both hemisphere monofractal behaviour is indicated by that data and void probability also shows good scaling behaviour. This suggests that a possible correlation of void probability with fractal behaviour of target residues. (author)

  16. Maneuver Analysis and Targeting Strategy for the Stardust Re-Entry Capsule

    Science.gov (United States)

    Helfrich, Cliff; Bhat, Ramachand S.; Kangas, Julie A.; Wilson, Roby S.; Wong, Mau C.; Potts, Christopher L.; Williams, Kenneth E.

    2006-01-01

    The Stardust Sample Return Capsule (SRC) returned to Earth on January 15, 2006 after seven years of collecting interstellar and comet particles over three heliocentric revolutions, as shown in Figure 1. The SRC was carried on board the Stardust spacecraft, as shown in Figure 2. Because the spacecraft was built with unbalanced thrusters, turns and attitude control maintenance resulted in undesirable delta-v being imparted to the trajectory. As a result, a carefully planned maneuver strategy was devised to accurately target the Stardust capsule to the Utah Test and Training Range (UTTR). This paper provides an overview of the Stardust spacecraft and mission and describes the maneuver strategy that was employed to achieve the stringent targeting requirements for landing in Utah. In addition, an overview of Stardust maneuver analysis tools and techniques will also be presented.

  17. Ranking of microRNA target prediction scores by Pareto front analysis.

    Science.gov (United States)

    Sahoo, Sudhakar; Albrecht, Andreas A

    2010-12-01

    Over the past ten years, a variety of microRNA target prediction methods has been developed, and many of the methods are constantly improved and adapted to recent insights into miRNA-mRNA interactions. In a typical scenario, different methods return different rankings of putative targets, even if the ranking is reduced to selected mRNAs that are related to a specific disease or cell type. For the experimental validation it is then difficult to decide in which order to process the predicted miRNA-mRNA bindings, since each validation is a laborious task and therefore only a limited number of mRNAs can be analysed. We propose a new ranking scheme that combines ranked predictions from several methods and - unlike standard thresholding methods - utilises the concept of Pareto fronts as defined in multi-objective optimisation. In the present study, we attempt a proof of concept by applying the new ranking scheme to hsa-miR-21, hsa-miR-125b, and hsa-miR-373 and prediction scores supplied by PITA and RNAhybrid. The scores are interpreted as a two-objective optimisation problem, and the elements of the Pareto front are ranked by the STarMir score with a subsequent re-calculation of the Pareto front after removal of the top-ranked mRNA from the basic set of prediction scores. The method is evaluated on validated targets of the three miRNA, and the ranking is compared to scores from DIANA-microT and TargetScan. We observed that the new ranking method performs well and consistent, and the first validated targets are elements of Pareto fronts at a relatively early stage of the recurrent procedure, which encourages further research towards a higher-dimensional analysis of Pareto fronts. Copyright © 2010 Elsevier Ltd. All rights reserved.

  18. Non-targeted analysis of unexpected food contaminants using LC-HRMS.

    Science.gov (United States)

    Kunzelmann, Marco; Winter, Martin; Åberg, Magnus; Hellenäs, Karl-Erik; Rosén, Johan

    2018-03-29

    A non-target analysis method for unexpected contaminants in food is described. Many current methods referred to as "non-target" are capable of detecting hundreds or even thousands of contaminants. However, they will typically still miss all other possible contaminants. Instead, a metabolomics approach might be used to obtain "true non-target" analysis. In the present work, such a method was optimized for improved detection capability at low concentrations. The method was evaluated using 19 chemically diverse model compounds spiked into milk samples to mimic unknown contamination. Other milk samples were used as reference samples. All samples were analyzed with UHPLC-TOF-MS (ultra-high-performance liquid chromatography time-of-flight mass spectrometry), using reversed-phase chromatography and electrospray ionization in positive mode. Data evaluation was performed by the software TracMass 2. No target lists of specific compounds were used to search for the contaminants. Instead, the software was used to sort out all features only occurring in the spiked sample data, i.e., the workflow resembled a metabolomics approach. Procedures for chemical identification of peaks were outside the scope of the study. Method, study design, and settings in the software were optimized to minimize manual evaluation and faulty or irrelevant hits and to maximize hit rate of the spiked compounds. A practical detection limit was established at 25 μg/kg. At this concentration, most compounds (17 out of 19) were detected as intact precursor ions, as fragments or as adducts. Only 2 irrelevant hits, probably natural compounds, were obtained. Limitations and possible practical use of the approach are discussed.

  19. Systems biology approaches and tools for analysis of interactomes and multi-target drugs.

    Science.gov (United States)

    Schrattenholz, André; Groebe, Karlfried; Soskic, Vukic

    2010-01-01

    Systems biology is essentially a proteomic and epigenetic exercise because the relatively condensed information of genomes unfolds on the level of proteins. The flexibility of cellular architectures is not only mediated by a dazzling number of proteinaceous species but moreover by the kinetics of their molecular changes: The time scales of posttranslational modifications range from milliseconds to years. The genetic framework of an organism only provides the blue print of protein embodiments which are constantly shaped by external input. Indeed, posttranslational modifications of proteins represent the scope and velocity of these inputs and fulfil the requirements of integration of external spatiotemporal signal transduction inside an organism. The optimization of biochemical networks for this type of information processing and storage results in chemically extremely fine tuned molecular entities. The huge dynamic range of concentrations, the chemical diversity and the necessity of synchronisation of complex protein expression patterns pose the major challenge of systemic analysis of biological models. One further message is that many of the key reactions in living systems are essentially based on interactions of moderate affinities and moderate selectivities. This principle is responsible for the enormous flexibility and redundancy of cellular circuitries. In complex disorders such as cancer or neurodegenerative diseases, which initially appear to be rooted in relatively subtle dysfunctions of multimodal physiologic pathways, drug discovery programs based on the concept of high affinity/high specificity compounds ("one-target, one-disease"), which has been dominating the pharmaceutical industry for a long time, increasingly turn out to be unsuccessful. Despite improvements in rational drug design and high throughput screening methods, the number of novel, single-target drugs fell much behind expectations during the past decade, and the treatment of "complex

  20. Inactivation of RNA viruses by gamma irradiation

    International Nuclear Information System (INIS)

    Nonomiya, Takashi; Morimoto, Akinori; Iwatsuki, Kazuo; Tsutsumi, Takamasa; Ito, Hitoshi; Yamashiro, Tomio; Ishigaki, Isao.

    1992-01-01

    Four kinds of RNA viruses, Bluetongue virus (BT), Bovine Virus Diarrhea-Mucosal Disease virus (BVD·MD), Bovine Respiratory Syncytial virus (RS), Vesicular Stmatitis virus (VS), were subjected to various doses of gamma irradiation to determine the lethal doses. The D 10 values, which are the dose necessary to decimally reduce infectivity, ranged from 1.5 to 3.4 kGy under frozen condition at dry-ice temperature, and they increased to 2.6 to 5.0 kGy under frozen condition at dry-ice temperature. Serum neutralzing antibody titer of Infectious Bovine Rhinotracheitis (IBR) was not adversely changed by the exposure to 36 kGy of gamma-rays under frozen condition. Analysis of electrophoresis patterns of the bovine serum also reveales that the serum proteins were not remarkably affected, even when exposed to 36 kGy of gamma radiation under frozen condition. The results suggested that gamma irradiation under frozen condition is an effective means for inactivating both DNA and RNA viruses without adversely affecting serum proteins and neutralizing antibody titer. (author)

  1. Inactivation of RNA viruses by gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Nonomiya, Takashi; Morimoto, Akinori; Iwatsuki, Kazuo; Tsutsumi, Takamasa (Ministry of Agriculture, Forestry and fisheries, Yokohama, Kanagawa (Japan). Animal Quarantine Service); Ito, Hitoshi; Yamashiro, Tomio; Ishigaki, Isao

    1992-09-01

    Four kinds of RNA viruses, Bluetongue virus (BT), Bovine Virus Diarrhea-Mucosal Disease virus (BVD[center dot]MD), Bovine Respiratory Syncytial virus (RS), Vesicular Stmatitis virus (VS), were subjected to various doses of gamma irradiation to determine the lethal doses. The D[sub 10] values, which are the dose necessary to decimally reduce infectivity, ranged from 1.5 to 3.4 kGy under frozen condition at dry-ice temperature, and they increased to 2.6 to 5.0 kGy under frozen condition at dry-ice temperature. Serum neutralzing antibody titer of Infectious Bovine Rhinotracheitis (IBR) was not adversely changed by the exposure to 36 kGy of gamma-rays under frozen condition. Analysis of electrophoresis patterns of the bovine serum also reveales that the serum proteins were not remarkably affected, even when exposed to 36 kGy of gamma radiation under frozen condition. The results suggested that gamma irradiation under frozen condition is an effective means for inactivating both DNA and RNA viruses without adversely affecting serum proteins and neutralizing antibody titer. (author).

  2. A Multimodal Data Analysis Approach for Targeted Drug Discovery Involving Topological Data Analysis (TDA).

    Science.gov (United States)

    Alagappan, Muthuraman; Jiang, Dadi; Denko, Nicholas; Koong, Albert C

    In silico drug discovery refers to a combination of computational techniques that augment our ability to discover drug compounds from compound libraries. Many such techniques exist, including virtual high-throughput screening (vHTS), high-throughput screening (HTS), and mechanisms for data storage and querying. However, presently these tools are often used independent of one another. In this chapter, we describe a new multimodal in silico technique for the hit identification and lead generation phases of traditional drug discovery. Our technique leverages the benefits of three independent methods-virtual high-throughput screening, high-throughput screening, and structural fingerprint analysis-by using a fourth technique called topological data analysis (TDA). We describe how a compound library can be independently tested with vHTS, HTS, and fingerprint analysis, and how the results can be transformed into a topological data analysis network to identify compounds from a diverse group of structural families. This process of using TDA or similar clustering methods to identify drug leads is advantageous because it provides a mechanism for choosing structurally diverse compounds while maintaining the unique advantages of already established techniques such as vHTS and HTS.

  3. Inactivation of pathogenic bacteria in food matrices: high pressure processing, photodynamic inactivation and pressure-assisted photodynamic inactivation

    Science.gov (United States)

    Cunha, A.; Couceiro, J.; Bonifácio, D.; Martins, C.; Almeida, A.; Neves, M. G. P. M. S.; Faustino, M. A. F.; Saraiva, J. A.

    2017-09-01

    Traditional food processing methods frequently depend on the application of high temperature. However, heat may cause undesirable changes in food properties and often has a negative impact on nutritional value and organoleptic characteristics. Therefore, reducing the microbial load without compromising the desirable properties of food products is still a technological challenge. High-pressure processing (HPP) can be classified as a cold pasteurization technique, since it is a non-thermal food preservation method that uses hydrostatic pressure to inactivate spoilage microorganisms. At the same time, it increases shelf life and retains the original features of food. Photodynamic inactivation (PDI) is also regarded as promising approach for the decontamination of food matrices. In this case, the inactivation of bacterial cells is achieved by the cytotoxic effects of reactive oxygens species (ROS) produced from the combined interaction of a photosensitizer molecule, light and oxygen. This short review examines some recent developments on the application of HPP and PDI with food-grade photosensitizers for the inactivation of listeriae, taken as a food pathogen model. The results of a proof-of-concept trial of the use of high-pressure as a coadjutant to increase the efficiency of photodynamic inactivation of bacterial endospores is also addressed.

  4. Human milk inactivates pathogens individually, additively, and synergistically.

    Science.gov (United States)

    Isaacs, Charles E

    2005-05-01

    Breast-feeding can reduce the incidence and the severity of gastrointestinal and respiratory infections in the suckling neonate by providing additional protective factors to the infant's mucosal surfaces. Human milk provides protection against a broad array of infectious agents through redundancy. Protective factors in milk can target multiple early steps in pathogen replication and target each step with more than one antimicrobial compound. The antimicrobial activity in human milk results from protective factors working not only individually but also additively and synergistically. Lipid-dependent antimicrobial activity in milk results from the additive activity of all antimicrobial lipids and not necessarily the concentration of one particular lipid. Antimicrobial milk lipids and peptides can work synergistically to decrease both the concentrations of individual compounds required for protection and, as importantly, greatly reduce the time needed for pathogen inactivation. The more rapidly pathogens are inactivated the less likely they are to establish an infection. The total antimicrobial protection provided by human milk appears to be far more than can be elucidated by examining protective factors individually.

  5. Virus inactivation studies using ion beams, electron and gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Smolko, Eduardo E. [Laboratorio de Polimeros, Grupo Aplicaciones Industriales, Unidad de Aplicaciones Tecnologicas y Agropecuarias, Centro Atomico Ezeiza, Comision Nacional de Energia Atomica, Pbro. Juan Gonzalez y Aragon 15, C.P. B1802AYA Ezeiza, Buenos Aires (Argentina)]. E-mail: smolko@cae.cnea.gov.ar; Lombardo, Jorge H. [Biotech S.A., C.P. 1754 Buenos Aires (Argentina)

    2005-07-01

    Known methods of virus inactivation are based on the chemical action of some substances such as acetylethylenimine, betapropiolactone, glycidalaldehyde, formaldehyde, etc. In such a process, the viral suspension should be kept at room or higher temperatures for 24-48 h. Under these conditions, physical and chemical agents act to degrade the virus antigenic proteins. On the contrary with ionizing radiations at low temperatures, the treatment does not cause such degradation allowing the study of different viral functions. In this work, particle ({alpha}, d and ss) and {gamma} irradiations were used for partial and total inactivation of Foot and Mouth Disease Virus (FMDV), Rauscher Leukemia Virus (RLV) and Herpes Simplex Virus (HSV). Obtention of the D{sub 37} dose from survival curves and the application of the target theory, permitted the determination of molecular weight of the nucleic acid genomes, EBR values and useful information for vaccine preparation. For RLV virus, a two target model of the RNA genome was deduced in accordance with biological information while from data from the literature and our own work on the structure of the scrapie prion, considering the molecular weight obtained by application of the theory, a new model for prion replication is presented, based on a trimer molecule.

  6. Virus inactivation studies using ion beams, electron and gamma irradiation

    International Nuclear Information System (INIS)

    Smolko, Eduardo E.; Lombardo, Jorge H.

    2005-01-01

    Known methods of virus inactivation are based on the chemical action of some substances such as acetylethylenimine, betapropiolactone, glycidalaldehyde, formaldehyde, etc. In such a process, the viral suspension should be kept at room or higher temperatures for 24-48 h. Under these conditions, physical and chemical agents act to degrade the virus antigenic proteins. On the contrary with ionizing radiations at low temperatures, the treatment does not cause such degradation allowing the study of different viral functions. In this work, particle (α, d and ss) and γ irradiations were used for partial and total inactivation of Foot and Mouth Disease Virus (FMDV), Rauscher Leukemia Virus (RLV) and Herpes Simplex Virus (HSV). Obtention of the D 37 dose from survival curves and the application of the target theory, permitted the determination of molecular weight of the nucleic acid genomes, EBR values and useful information for vaccine preparation. For RLV virus, a two target model of the RNA genome was deduced in accordance with biological information while from data from the literature and our own work on the structure of the scrapie prion, considering the molecular weight obtained by application of the theory, a new model for prion replication is presented, based on a trimer molecule

  7. Next-to leading order analysis of target mass corrections to structure functions and asymmetries

    International Nuclear Information System (INIS)

    Brady, L.T.; Accardi, A.; Hobbs, T.J.; Melnitchouk, W.

    2011-01-01

    We perform a comprehensive analysis of target mass corrections (TMCs) to spin-averaged structure functions and asymmetries at next-to-leading order. Several different prescriptions for TMCs are considered, including the operator product expansion, and various approximations to it, collinear factorization, and xi-scaling. We assess the impact of each of these on a number of observables, such as the neutron to proton F 2 structure function ratio, and parity-violating electron scattering asymmetries for protons and deuterons which are sensitive to gamma-Z interference effects. The corrections from higher order radiative and nuclear effects on the parity-violating deuteron asymmetry are also quantified.

  8. Theory of error for target factor analysis with applications to mass spectrometry and nuclear magnetic resonance spectrometry

    International Nuclear Information System (INIS)

    Malinowski, E.R.

    1978-01-01

    Based on the theory of error for abstract factor analysis described earlier, a theory of error for target factor analysis is developed. The theory shows how the error in the data matrix mixes with the error in the target test vector. The apparent error in a target test is found to be a vector sum of the real error in the target vector and the real error in the predicted vector. The theory predicts the magnitudes of these errors without requiring any a priori knowledge of the error in the data matrix or the target vector. A reliability function and a spoil function are developed for the purpose of assessing the validity and the worthiness of a target vector. Examples from model data, mass spectrometry and nuclear magnetic resonance spectrometry are presented. (Auth.)

  9. Extending in silico mechanism-of-action analysis by annotating targets with pathways: application to cellular cytotoxicity readouts.

    Science.gov (United States)

    Liggi, Sonia; Drakakis, Georgios; Koutsoukas, Alexios; Cortes-Ciriano, Isidro; Martínez-Alonso, Patricia; Malliavin, Thérèse E; Velazquez-Campoy, Adrian; Brewerton, Suzanne C; Bodkin, Michael J; Evans, David A; Glen, Robert C; Carrodeguas, José Alberto; Bender, Andreas

    2014-01-01

    An in silico mechanism-of-action analysis protocol was developed, comprising molecule bioactivity profiling, annotation of predicted targets with pathways and calculation of enrichment factors to highlight targets and pathways more likely to be implicated in the studied phenotype. The method was applied to a cytotoxicity phenotypic endpoint, with enriched targets/pathways found to be statistically significant when compared with 100 random datasets. Application on a smaller apoptotic set (10 molecules) did not allowed to obtain statistically relevant results, suggesting that the protocol requires modification such as analysis of the most frequently predicted targets/annotated pathways. Pathway annotations improved the mechanism-of-action information gained by target prediction alone, allowing a better interpretation of the predictions and providing better mapping of targets onto pathways.

  10. Antimalarial drug targets in Plasmodium falciparum predicted by stage-specific metabolic network analysis

    Directory of Open Access Journals (Sweden)

    Huthmacher Carola

    2010-08-01

    Full Text Available Abstract Background Despite enormous efforts to combat malaria the disease still afflicts up to half a billion people each year of which more than one million die. Currently no approved vaccine is available and resistances to antimalarials are widely spread. Hence, new antimalarial drugs are urgently needed. Results Here, we present a computational analysis of the metabolism of Plasmodium falciparum, the deadliest malaria pathogen. We assembled a compartmentalized metabolic model and predicted life cycle stage specific metabolism with the help of a flux balance approach that integrates gene expression data. Predicted metabolite exchanges between parasite and host were found to be in good accordance with experimental findings when the parasite's metabolic network was embedded into that of its host (erythrocyte. Knock-out simulations identified 307 indispensable metabolic reactions within the parasite. 35 out of 57 experimentally demonstrated essential enzymes were recovered and another 16 enzymes, if additionally the assumption was made that nutrient uptake from the host cell is limited and all reactions catalyzed by the inhibited enzyme are blocked. This predicted set of putative drug targets, shown to be enriched with true targets by a factor of at least 2.75, was further analyzed with respect to homology to human enzymes, functional similarity to therapeutic targets in other organisms and their predicted potency for prophylaxis and disease treatment. Conclusions The results suggest that the set of essential enzymes predicted by our flux balance approach represents a promising starting point for further drug development.

  11. Analysis of the Chirplet Transform-Based Algorithm for Radar Detection of Accelerated Targets

    Science.gov (United States)

    Galushko, V. G.; Vavriv, D. M.

    2017-06-01

    Purpose: Efficiency analysis of an optimal algorithm of chirp signal processing based on the chirplet transform as applied to detection of radar targets in uniformly accelerated motion. Design/methodology/approach: Standard methods of the optimal filtration theory are used to investigate the ambiguity function of chirp signals. Findings: An analytical expression has been derived for the ambiguity function of chirp signals that is analyzed with respect to detection of radar targets moving at a constant acceleration. Sidelobe level and characteristic width of the ambiguity function with respect to the coordinates frequency and rate of its change have been estimated. The gain in the signal-to-noise ratio has been assessed that is provided by the algorithm under consideration as compared with application of the standard Fourier transform to detection of chirp signals against a “white” noise background. It is shown that already with a comparatively small (processing channels (elementary filters with respect to the frequency change rate) the gain in the signal-tonoise ratio exceeds 10 dB. A block diagram of implementation of the algorithm under consideration is suggested on the basis of a multichannel weighted Fourier transform. Recommendations as for selection of the detection algorithm parameters have been developed. Conclusions: The obtained results testify to efficiency of application of the algorithm under consideration to detection of radar targets moving at a constant acceleration. Nevertheless, it seems expedient to perform computer simulations of its operability with account for the noise impact along with trial measurements in real conditions.

  12. Theoretical analysis of recirculation zone and buffer zone in the ADS windowless spallation target

    International Nuclear Information System (INIS)

    Liu, Jie; Pan, Chang-zhao; Tong, Jian-fei; Lu, Wen-qiang

    2015-01-01

    Highlights: • Height of recirculation zone is very important in windowless target design. • A theoretical formula for the height is derived based on the Bernoulli equation. • Numerical simulation for the LBE is performed and the height of recirculation zone is also obtained. • The theoretically-derived simulation-predicted recirculation zone heights agree with each other very well and the theoretical derivation is proved to be correct. - Abstract: The thermo-hydraulic analysis including reduction of the height of recirculation zone and stability of the free surface is very important in the design and optimization of ADS windowless spallation targets. In the present study, the Bernoulli equation is used to analyze the entire flow process in the target. Formulae for the height of the recirculation zone and the buffer zone are both obtained explicitly. Furthermore, numerical simulation for the heavy metal lead–bismuth eutectic liquid and vapor with cavitation phase change is also performed, and a novel method to calculate the height of the recirculation zone is put forward. By comparison of the theoretical formulae and numerical results, it is clearly shown that they agree with each other very well, and the heights predicted by the two methods are both determined by their own upstream flow parameters

  13. Accurate Analysis of Target Characteristic in Bistatic SAR Images: A Dihedral Corner Reflectors Case

    Directory of Open Access Journals (Sweden)

    Dongyang Ao

    2017-12-01

    Full Text Available The dihedral corner reflectors are the basic geometric structure of many targets and are the main contributions of radar cross section (RCS in the synthetic aperture radar (SAR images. In stealth technologies, the elaborate design of the dihedral corners with different opening angles is a useful approach to reduce the high RCS generated by multiple reflections. As bistatic synthetic aperture sensors have flexible geometric configurations and are sensitive to the dihedral corners with different opening angles, they specially fit for the stealth target detections. In this paper, the scattering characteristic of dihedral corner reflectors is accurately analyzed in bistatic synthetic aperture images. The variation of RCS with the changing opening angle is formulated and the method to design a proper bistatic radar for maximizing the detection capability is provided. Both the results of the theoretical analysis and the experiments show the bistatic SAR could detect the dihedral corners, under a certain bistatic angle which is related to the geometry of target structures.

  14. Accurate Analysis of Target Characteristic in Bistatic SAR Images: A Dihedral Corner Reflectors Case

    Science.gov (United States)

    Ao, Dongyang; Hu, Cheng; Tian, Weiming

    2017-01-01

    The dihedral corner reflectors are the basic geometric structure of many targets and are the main contributions of radar cross section (RCS) in the synthetic aperture radar (SAR) images. In stealth technologies, the elaborate design of the dihedral corners with different opening angles is a useful approach to reduce the high RCS generated by multiple reflections. As bistatic synthetic aperture sensors have flexible geometric configurations and are sensitive to the dihedral corners with different opening angles, they specially fit for the stealth target detections. In this paper, the scattering characteristic of dihedral corner reflectors is accurately analyzed in bistatic synthetic aperture images. The variation of RCS with the changing opening angle is formulated and the method to design a proper bistatic radar for maximizing the detection capability is provided. Both the results of the theoretical analysis and the experiments show the bistatic SAR could detect the dihedral corners, under a certain bistatic angle which is related to the geometry of target structures. PMID:29271917

  15. Inactivation of enteroviruses in sewage with ozone

    Energy Technology Data Exchange (ETDEWEB)

    Ivanova, O.E.; Bogdanov, M.V.; Kazantseva, V.A.; Gabrilevskaia, L.N.; Kodkind, G.K.H.

    The study of ozone inactivation of enteroviruses in sewage showed the presence in sewage of suspensions of organic origin and bacterial flora to influence the rate of inactivation. The inactivation rate of poliomyelitis virus in sewage free from organic suspension and bacterial flora was significantly higher than that in sewage containing such suspension and bacterial flora. The inactivation rate of enteroviruses was found not to depend upon the protein and salt composition and pH of sewage or strain appurtenance of viruses. The inactivation rate of enteroviruses directly depended upon the dose of ozone and time of contact with it. Differences in the resistance of different types of poliomyelitis virus, ECHO and Coxsackie viruses to the effect of ozone are likely exist. These differences are manifested within the range of relatively small doses of ozone. E. coli is more resistant to ozone than entero-viruses. The results of laboratory studies were used to choose the regimen of sanitation of urban sewage to be used in technological cycles of industrial enterprises.

  16. Inactivation of Mycobacterium avium with free chlorine.

    Science.gov (United States)

    Luh, Jeanne; Mariñas, Benito J

    2007-07-15

    The inactivation kinetics of Mycobacterium avium with free chlorine was characterized by two stages: an initial phase at a relatively fast rate followed by a slower second stage of pseudo first-order kinetics. The inactivation rate of each stage was approximately the same for all experiments performed at a certain condition of pH and temperature; however, variability was observed for the disinfectant exposure at which the transition between the two stages occurred. This variability was not a function of the initial disinfectant concentration, the initial bacterial density, or the bacterial stock. However, the transition to the second stage varied more significantly at high temperatures (30 degrees C), while lower variability was observed at lower temperatures (5 and 20 degrees C). Experiments conducted at pH values in the range of 6-9 revealed that the inactivation of M. avium was primarily due to hypochlorous acid, with little contribution from hypochlorite ion within this pH range. The inactivation kinetics was represented with a two-population model. The activation energies for the resulting pseudo first-order rate constants for the populations with fast and slow kinetics were 100.3 and 96.5 kJ/mol, respectively. The magnitude of these values suggested that for waters of relatively high pH and low temperatures, little inactivation of M. avium would be achieved within treatment plants, providing a seeding source for distribution systems.

  17. Human microRNA target analysis and gene ontology clustering by GOmir, a novel stand-alone application.

    Science.gov (United States)

    Roubelakis, Maria G; Zotos, Pantelis; Papachristoudis, Georgios; Michalopoulos, Ioannis; Pappa, Kalliopi I; Anagnou, Nicholas P; Kossida, Sophia

    2009-06-16

    microRNAs (miRNAs) are single-stranded RNA molecules of about 20-23 nucleotides length found in a wide variety of organisms. miRNAs regulate gene expression, by interacting with target mRNAs at specific sites in order to induce cleavage of the message or inhibit translation. Predicting or verifying mRNA targets of specific miRNAs is a difficult process of great importance. GOmir is a novel stand-alone application consisting of two separate tools: JTarget and TAGGO. JTarget integrates miRNA target prediction and functional analysis by combining the predicted target genes from TargetScan, miRanda, RNAhybrid and PicTar computational tools as well as the experimentally supported targets from TarBase and also providing a full gene description and functional analysis for each target gene. On the other hand, TAGGO application is designed to automatically group gene ontology annotations, taking advantage of the Gene Ontology (GO), in order to extract the main attributes of sets of proteins. GOmir represents a new tool incorporating two separate Java applications integrated into one stand-alone Java application. GOmir (by using up to five different databases) introduces miRNA predicted targets accompanied by (a) full gene description, (b) functional analysis and (c) detailed gene ontology clustering. Additionally, a reverse search initiated by a potential target can also be conducted. GOmir can freely be downloaded BRFAA.

  18. “Redundancy” of Endocannabinoid Inactivation: New Challenges and Opportunities for Pain Control

    Science.gov (United States)

    2012-01-01

    Redundancy of metabolic pathways and molecular targets is a typical feature of all lipid mediators, and endocannabinoids, which were originally defined as endogenous agonists at cannabinoid CB1 and CB2 receptors, are no exception. In particular, the two most studied endocannabinoids, anandamide and 2-arachidonoylglycerol, are inactivated through alternative biochemical routes, including hydrolysis and oxidation, and more than one enzyme might be used even for the same type of inactivating reaction. These enzymes also recognize as substrates other concurrent lipid mediators, whereas, in turn, endocannabinoids might interact with noncannabinoid receptors with subcellular distribution and ultimate biological actions either similar to or completely different from those of cannabinoid receptors. Even splicing variants of endocannabinoid hydrolyzing enzymes, such as FAAH-1, might play distinct roles in endocannabinoid inactivation. Finally, the products of endocannabinoid catabolism may have their own targets, with biological roles different from those of cannabinoid receptors. These peculiarities of endocannabinoid signaling have complicated the use of inhibitors of its inactivation mechanisms as a safer and more efficacious alternative to the direct targeting of cannabinoid receptors for the treatment of several pathological conditions, including pain. However, new strategies, including the rediscovery of “dirty drugs”, and the use of certain natural products (including non-THC cannabis constituents), are emerging that might allow us to make a virtue of necessity and exploit endocannabinoid redundancy to develop new analgesics. PMID:22860203

  19. Small UAS Analysis of Laser Designation and Search and Target Acquisition Capabilities in an Urban Environment

    National Research Council Canada - National Science Library

    Harclerode, Eric

    2008-01-01

    Conclusions: -Small UAS has extreme difficulty lasing moving targets in high density urban environments -Lasing moving targets in medium density terrain is possible but not certain -Lasing of stationary targets...

  20. Physical Activity Targeted at Maximal Lipid Oxidation: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    A. J. Romain

    2012-01-01

    Full Text Available Exercise is recognized as a part of the management of obesity and diabetes. Various protocols of exercise are proposed for the management of obesity, diabetes, and other metabolic diseases. One of the strategies proposed by several authors is low intensity endurance training targeted at the level of maximal oxidation. Large series using this technique are lacking. Addressing this issue, we performed a meta-analysis of the studies on anthropometric measurements. From a database of 433 articles, 15 were selected, including 279 subjects with 6 different populations. Studies duration ranged from 2 months to 12 months. Concerning weight loss, in the intervention versus control analysis, five studies with 185 participants were included with a significant effect size favors exercise (P=0.02 without significant heterogeneity (I2=0.0%, P=0.83. Further randomized controlled trials for comparing it with other exercise protocols and defining its dose effectiveness on large samples are needed.

  1. Sensitivity analysis of intracellular signaling pathway kinetics predicts targets for stem cell fate control.

    Directory of Open Access Journals (Sweden)

    Alborz Mahdavi

    2007-07-01

    Full Text Available Directing stem cell fate requires knowledge of how signaling networks integrate temporally and spatially segregated stimuli. We developed and validated a computational model of signal transducer and activator of transcription-3 (Stat3 pathway kinetics, a signaling network involved in embryonic stem cell (ESC self-renewal. Our analysis identified novel pathway responses; for example, overexpression of the receptor glycoprotein-130 results in reduced pathway activation and increased ESC differentiation. We used a systematic in silico screen to identify novel targets and protein interactions involved in Stat3 activation. Our analysis demonstrates that signaling activation and desensitization (the inability to respond to ligand restimulation is regulated by balancing the activation state of a distributed set of parameters including nuclear export of Stat3, nuclear phosphatase activity, inhibition by suppressor of cytokine signaling, and receptor trafficking. This knowledge was used to devise a temporally modulated ligand delivery strategy that maximizes signaling activation and leads to enhanced ESC self-renewal.

  2. A new robustness analysis for climate policy evaluations: A CGE application for the EU 2020 targets

    International Nuclear Information System (INIS)

    Hermeling, Claudia; Löschel, Andreas; Mennel, Tim

    2013-01-01

    This paper introduces a new method for stochastic sensitivity analysis for computable general equilibrium (CGE) model based on Gauss Quadrature and applies it to check the robustness of a large-scale climate policy evaluation. The revised version of the Gauss-quadrature approach to sensitivity analysis reduces computations considerably vis-à-vis the commonly applied Monte-Carlo methods; this allows for a stochastic sensitivity analysis also for large scale models and multi-dimensional changes of parameters. In the application, an impact assessment of EU2020 climate policy, we focus on sectoral elasticities that are part of the basic parameters of the model and have been recently determined by econometric estimation, alongside with standard errors. The impact assessment is based on the large scale CGE model PACE. We show the applicability of the Gauss-quadrature approach and confirm the robustness of the impact assessment with the PACE model. The variance of the central model outcomes is smaller than their mean by order four to eight, depending on the aggregation level (i.e. aggregate variables such as GDP show a smaller variance than sectoral output). - Highlights: ► New, simplified method for stochastic sensitivity analysis for CGE analysis. ► Gauss quadrature with orthogonal polynomials. ► Application to climate policy—the case of the EU 2020 targets

  3. Identification of BAG3 target proteins in anaplastic thyroid cancer cells by proteomic analysis.

    Science.gov (United States)

    Galdiero, Francesca; Bello, Anna Maria; Spina, Anna; Capiluongo, Anna; Liuu, Sophie; De Marco, Margot; Rosati, Alessandra; Capunzo, Mario; Napolitano, Maria; Vuttariello, Emilia; Monaco, Mario; Califano, Daniela; Turco, Maria Caterina; Chiappetta, Gennaro; Vinh, Joëlle; Chiappetta, Giovanni

    2018-01-30

    BAG3 protein is an apoptosis inhibitor and is highly expressed in Anaplastic Thyroid Cancer. We investigated the entire set of proteins modulated by BAG3 silencing in the human anaplastic thyroid 8505C cancer cells by using the Stable-Isotope Labeling by Amino acids in Cell culture strategy combined with mass spectrometry analysis. By this approach we identified 37 up-regulated and 54 down-regulated proteins in BAG3-silenced cells. Many of these proteins are reportedly involved in tumor progression, invasiveness and resistance to therapies. We focused our attention on an oncogenic protein, CAV1, and a tumor suppressor protein, SERPINB2, that had not previously been reported to be modulated by BAG3. Their expression levels in BAG3-silenced cells were confirmed by qRT-PCR and western blot analyses, disclosing two novel targets of BAG3 pro-tumor activity. We also examined the dataset of proteins obtained by the quantitative proteomics analysis using two tools, Downstream Effect Analysis and Upstream Regulator Analysis of the Ingenuity Pathways Analysis software. Our analyses confirm the association of the proteome profile observed in BAG3-silenced cells with an increase in cell survival and a decrease in cell proliferation and invasion, and highlight the possible involvement of four tumor suppressor miRNAs and TP53/63 proteins in BAG3 activity.

  4. Integrated network analysis reveals potentially novel molecular mechanisms and therapeutic targets of refractory epilepsies.

    Directory of Open Access Journals (Sweden)

    Hongwei Chu

    Full Text Available Epilepsy is a complex neurological disorder and a significant health problem. The pathogenesis of epilepsy remains obscure in a significant number of patients and the current treatment options are not adequate in about a third of individuals which were known as refractory epilepsies (RE. Network medicine provides an effective approach for studying the molecular mechanisms underlying complex diseases. Here we integrated 1876 disease-gene associations of RE and located those genes to human protein-protein interaction (PPI network to obtain 42 significant RE-associated disease modules. The functional analysis of these disease modules showed novel molecular pathological mechanisms of RE, such as the novel enriched pathways (e.g., "presynaptic nicotinic acetylcholine receptors", "signaling by insulin receptor". Further analysis on the relationships between current drug targets and the RE-related disease genes showed the rational mechanisms of most antiepileptic drugs. In addition, we detected ten potential novel drug targets (e.g., KCNA1, KCNA4-6, KCNC3, KCND2, KCNMA1, CAMK2G, CACNB4 and GRM1 located in three RE related disease modules, which might provide novel insights into the new drug discovery for RE therapy.

  5. Sejong Open Cluster Survey (SOS). 0. Target Selection and Data Analysis

    Science.gov (United States)

    Sung, Hwankyung; Lim, Beomdu; Bessell, Michael S.; Kim, Jinyoung S.; Hur, Hyeonoh; Chun, Moo-Young; Park, Byeong-Gon

    2013-06-01

    Star clusters are superb astrophysical laboratories containing cospatial and coeval samples of stars with similar chemical composition. We initiate the Sejong Open cluster Survey (SOS) - a project dedicated to providing homogeneous photometry of a large number of open clusters in the SAAO Johnson-Cousins' UBVI system. To achieve our main goal, we pay much attention to the observation of standard stars in order to reproduce the SAAO standard system. Many of our targets are relatively small sparse clusters that escaped previous observations. As clusters are considered building blocks of the Galactic disk, their physical properties such as the initial mass function, the pattern of mass segregation, etc. give valuable information on the formation and evolution of the Galactic disk. The spatial distribution of young open clusters will be used to revise the local spiral arm structure of the Galaxy. In addition, the homogeneous data can also be used to test stellar evolutionary theory, especially concerning rare massive stars. In this paper we present the target selection criteria, the observational strategy for accurate photometry, and the adopted calibrations for data analysis such as color-color relations, zero-age main sequence relations, Sp - M_V relations, Sp - T_{eff} relations, Sp - color relations, and T_{eff} - BC relations. Finally we provide some data analysis such as the determination of the reddening law, the membership selection criteria, and distance determination.

  6. The inactivation of the sortilin gene leads to a partial disruption of prosaposin trafficking to the lysosomes

    International Nuclear Information System (INIS)

    Zeng, Jibin; Racicott, Jesse; Morales, Carlos R.

    2009-01-01

    Lysosomes are intracellular organelles which contain enzymes and activator proteins involved in the digestion and recycling of a variety of cellular and extracellular substances. We have identified a novel sorting receptor, sortilin, which is involved in the lysosomal trafficking of the sphingolipid activator proteins, prosaposin and GM 2 AP, and the soluble hydrolases cathepsin D, cathepsin H, and acid sphingomyelinase. Sortilin belongs to a growing family of receptors with homology to the yeast Vps10 protein, which acts as a lysosomal sorting receptor for carboxypeptidase Y. In this study we examined the effects of the sortilin gene inactivation in mice. The inactivation of this gene did not yield any noticeable lysosomal pathology. To determine the existence of an alternative receptor complementing the sorting function of sortilin, we quantified the concentration of prosaposin in the lysosomes of the nonciliated epithelial cells lining the efferent ducts. These cells were chosen because they express sortilin and have a large number of lysosomes containing prosaposin. In addition, the nonciliated cells are known to endocytose luminal prosaposin that is synthesized and secreted by Sertoli cells into the seminiferous luminal fluids. Consequently, the nonciliated cells are capable of targeting both exogenous and endogenous prosaposin to the lysosomes. Using electron microscope immunogold labeling and quantitative analysis, our results demonstrate that inactivation of the sortilin gene produces a significant decrease of prosaposin in the lysosomes. When luminal prosaposin was excluded from the efferent ducts, the level of prosaposin in lysosomes was even lower in the mutant mice. Nonetheless, a significant amount of prosaposin continues to reach the lysosomal compartment. These results strongly suggest the existence of an alternative receptor that complements the function of sortilin and explains the lack of lysosomal storage disorders in the sortilin-deficient mice.

  7. The inactivation of the sortilin gene leads to a partial disruption of prosaposin trafficking to the lysosomes

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Jibin; Racicott, Jesse [Department of Anatomy and Cell Biology, McGill University, Montreal (Canada); Morales, Carlos R., E-mail: carlos.morales@mcgill.ca [Department of Anatomy and Cell Biology, McGill University, Montreal (Canada)

    2009-11-01

    Lysosomes are intracellular organelles which contain enzymes and activator proteins involved in the digestion and recycling of a variety of cellular and extracellular substances. We have identified a novel sorting receptor, sortilin, which is involved in the lysosomal trafficking of the sphingolipid activator proteins, prosaposin and GM{sub 2}AP, and the soluble hydrolases cathepsin D, cathepsin H, and acid sphingomyelinase. Sortilin belongs to a growing family of receptors with homology to the yeast Vps10 protein, which acts as a lysosomal sorting receptor for carboxypeptidase Y. In this study we examined the effects of the sortilin gene inactivation in mice. The inactivation of this gene did not yield any noticeable lysosomal pathology. To determine the existence of an alternative receptor complementing the sorting function of sortilin, we quantified the concentration of prosaposin in the lysosomes of the nonciliated epithelial cells lining the efferent ducts. These cells were chosen because they express sortilin and have a large number of lysosomes containing prosaposin. In addition, the nonciliated cells are known to endocytose luminal prosaposin that is synthesized and secreted by Sertoli cells into the seminiferous luminal fluids. Consequently, the nonciliated cells are capable of targeting both exogenous and endogenous prosaposin to the lysosomes. Using electron microscope immunogold labeling and quantitative analysis, our results demonstrate that inactivation of the sortilin gene produces a significant decrease of prosaposin in the lysosomes. When luminal prosaposin was excluded from the efferent ducts, the level of prosaposin in lysosomes was even lower in the mutant mice. Nonetheless, a significant amount of prosaposin continues to reach the lysosomal compartment. These results strongly suggest the existence of an alternative receptor that complements the function of sortilin and explains the lack of lysosomal storage disorders in the sortilin

  8. An integrative genomic and transcriptomic analysis reveals potential targets associated with cell proliferation in uterine leiomyomas.

    Directory of Open Access Journals (Sweden)

    Priscila Daniele Ramos Cirilo

    Full Text Available Uterine Leiomyomas (ULs are the most common benign tumours affecting women of reproductive age. ULs represent a major problem in public health, as they are the main indication for hysterectomy. Approximately 40-50% of ULs have non-random cytogenetic abnormalities, and half of ULs may have copy number alterations (CNAs. Gene expression microarrays studies have demonstrated that cell proliferation genes act in response to growth factors and steroids. However, only a few genes mapping to CNAs regions were found to be associated with ULs.We applied an integrative analysis using genomic and transcriptomic data to identify the pathways and molecular markers associated with ULs. Fifty-one fresh frozen specimens were evaluated by array CGH (JISTIC and gene expression microarrays (SAM. The CONEXIC algorithm was applied to integrate the data.The integrated analysis identified the top 30 significant genes (P<0.01, which comprised genes associated with cancer, whereas the protein-protein interaction analysis indicated a strong association between FANCA and BRCA1. Functional in silico analysis revealed target molecules for drugs involved in cell proliferation, including FGFR1 and IGFBP5. Transcriptional and protein analyses showed that FGFR1 (P = 0.006 and P<0.01, respectively and IGFBP5 (P = 0.0002 and P = 0.006, respectively were up-regulated in the tumours when compared with the adjacent normal myometrium.The integrative genomic and transcriptomic approach indicated that FGFR1 and IGFBP5 amplification, as well as the consequent up-regulation of the protein products, plays an important role in the aetiology of ULs and thus provides data for potential drug therapies development to target genes associated with cellular proliferation in ULs.

  9. Study on the inactivation of intracellular enzyme molecules by X-ray irradiation

    International Nuclear Information System (INIS)

    Lee, S.B.

    1977-01-01

    Inactivation of the glutamic acid dehydrogenase and glucose-6-phosphate dehydrogenase enzyme molecules in the Ehrlich ascites tumor cells of the mouse were studied. The above mentioned intracellular enzyme molecules were irradiated by the X-ray radiation under the condition of 65 kV, 1 Amp under the atmosphere of nitrogen gases and by 4 0 C. Thereby, irradiation doses were 580 KR/min(error: +-3%). After irradiation, the cell homogentes were prepared through liquid air techniques. There after, the activities of the enzymes were measured with photometric method given by O. Warburg and W. Christian. The dose effect curves of the activities of the two enzymes by the X-ray irradiation showed both exponential and the inactivation doses were 6.5x10 6 and 5.0x10 6 R respectively. These results showed one side that the inactivation process of the intracellular enzyme molecules was one hit reaction after target theory, and the other side that this inactivation process could not be the primary causes of the death through X-ray irradiation of the vertebrate animals, because of the high resistance of the intracellular protein molecules against X-ray irradiation. The one hit reaction by the inactivation process of the irradiated intracellular enzyme molecules was discussed. (author)

  10. Targeted drugs for pulmonary arterial hypertension: a network meta-analysis of 32 randomized clinical trials

    Directory of Open Access Journals (Sweden)

    Gao XF

    2017-05-01

    Full Text Available Xiao-Fei Gao,1 Jun-Jie Zhang,1,2 Xiao-Min Jiang,1 Zhen Ge,1,2 Zhi-Mei Wang,1 Bing Li,1 Wen-Xing Mao,1 Shao-Liang Chen1,2 1Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 2Department of Cardiology, Nanjing Heart Center, Nanjing, People’s Republic of China Background: Pulmonary arterial hypertension (PAH is a devastating disease and ultimately leads to right heart failure and premature death. A total of four classical targeted drugs, prostanoids, endothelin receptor antagonists (ERAs, phosphodiesterase 5 inhibitors (PDE-5Is, and soluble guanylate cyclase stimulator (sGCS, have been proved to improve exercise capacity and hemodynamics compared to placebo; however, direct head-to-head comparisons of these drugs are lacking. This network meta-analysis was conducted to comprehensively compare the efficacy of these targeted drugs for PAH.Methods: Medline, the Cochrane Library, and other Internet sources were searched for randomized clinical trials exploring the efficacy of targeted drugs for patients with PAH. The primary effective end point of this network meta-analysis was a 6-minute walk distance (6MWD.Results: Thirty-two eligible trials including 6,758 patients were identified. There was a statistically significant improvement in 6MWD, mean pulmonary arterial pressure, pulmonary vascular resistance, and clinical worsening events associated with each of the four targeted drugs compared with placebo. Combination therapy improved 6MWD by 20.94 m (95% confidence interval [CI]: 6.94, 34.94; P=0.003 vs prostanoids, and 16.94 m (95% CI: 4.41, 29.47; P=0.008 vs ERAs. PDE-5Is improved 6MWD by 17.28 m (95% CI: 1.91, 32.65; P=0.028 vs prostanoids, with a similar result with combination therapy. In addition, combination therapy reduced mean pulmonary artery pressure by 3.97 mmHg (95% CI: -6.06, -1.88; P<0.001 vs prostanoids, 8.24 mmHg (95% CI: -10.71, -5.76; P<0.001 vs ERAs, 3.38 mmHg (95% CI: -6.30, -0.47; P=0.023 vs

  11. UVA Causes Dual Inactivation of Cathepsin B and L Underlying Lysosomal Dysfunction in Human Dermal Fibroblasts

    Science.gov (United States)

    Lamore, Sarah D.; Wondrak, Georg T.

    2013-01-01

    Cutaneous exposure to chronic solar UVA-radiation is a causative factor in photocarcinogenesis and photoaging. Recently, we have identified the thiol-dependent cysteine-protease cathepsin B as a novel UVA-target undergoing photo-oxidative inactivation upstream of autophagic-lysosomal dysfunction in fibroblasts. In this study, we examined UVA effects on a wider range of cathepsins and explored the occurrence of UVA-induced cathepsin inactivation in other cultured skin cell types. In dermal fibroblasts, chronic exposure to non-cytotoxic doses of UVA caused pronounced inactivation of the lysosomal cysteine-proteases cathepsin B and L, effects not observed in primary keratinocytes and occurring only to a minor extent in primary melanocytes. In order to determine if UVA-induced lysosomal impairment requires single or dual inactivation of cathepsin B and/or L, we used a genetic approach (siRNA) to selectively downregulate enzymatic activity of these target cathepsins. Monitoring an established set of protein markers (including LAMP1, LC3-II, and p62) and cell ultrastructural changes detected by electron microscopy, we observed that only dual genetic antagonism (targeting both CTSB and CTSL expression) could mimic UVA-induced autophagic-lysosomal alterations, whereas single knockdown (targeting CTSB or CTSL only) did not display ‘UVA-mimetic’ effects failing to reproduce the UVA-induced phenotype. Taken together, our data demonstrate that chronic UVA inhibits both cathepsin B and L enzymatic activity and that dual inactivation of both enzymes is a causative factor underlying UVA-induced impairment of lysosomal function in dermal fibroblasts. PMID:23603447

  12. IFMIF Li target back-plate design integration and thermo-mechanical analysis

    International Nuclear Information System (INIS)

    Riccardi, B.; Roccella, S.; Micciche, G.

    2006-01-01

    The International Fusion Materials Irradiation Facility (IFMIF) is an accelerator-driven intense neutron source where fusion reactor candidate materials will be tested. The neutron flux is produced by means of a deuteron beam (current 250 mA, energy 40 MeV) that strikes a liquid lithium target circulating in a lithium loop. The support on which the liquid lithium flows, i.e. the back-plate, is the most heavily exposed component to neutron flux. A '' bayonet '' concept solution for the back-plate was proposed by ENEA with the objectives of improving the back-plate reliability and simplifying the remote handling procedures. On the base of this concept, a back-plate mock-up was fabricated and validated. Starting from the findings of the mock up design, a back-plate design integration exercise was carried out in order to check if the back-plate geometrical features are compatible with the target assembly and the Vertical Test Assemblies (VTA). The work carried out has demonstrated that even with the changes operated for the design integration (increase of in-plane dimensions and reduction of thickness) the bayonet concept is able to guarantee a tight connection to the target assembly. A thermo-mechanical analysis of the back-plate has been carried out by means of ABAQUS code. The thermal load used as input for the calculations, i.e. the neutron heat generation, has been estimated by means of Monte Carlo Mc-Delicious code. The two boundary constraint cases (full and minimum contact with target assembly) considered for each back-plate geometry option represent the extreme cases of the real operating condition of the plate. The influence of the contact heat exchange coefficient and the back-plate thickness has been also evaluated. For all these reasons, the results of the analysis can be considered as the domain of variability of the real working conditions. The results show that AISI 316L steel is not suitable as black-plate material: the stress induced in the plate, in

  13. Automated selected reaction monitoring data analysis workflow for large-scale targeted proteomic studies.

    Science.gov (United States)

    Surinova, Silvia; Hüttenhain, Ruth; Chang, Ching-Yun; Espona, Lucia; Vitek, Olga; Aebersold, Ruedi

    2013-08-01

    Targeted proteomics based on selected reaction monitoring (SRM) mass spectrometry is commonly used for accurate and reproducible quantification of protein analytes in complex biological mixtures. Strictly hypothesis-driven, SRM assays quantify each targeted protein by collecting measurements on its peptide fragment ions, called transitions. To achieve sensitive and accurate quantitative results, experimental design and data analysis must consistently account for the variability of the quantified transitions. This consistency is especially important in large experiments, which increasingly require profiling up to hundreds of proteins over hundreds of samples. Here we describe a robust and automated workflow for the analysis of large quantitative SRM data sets that integrates data processing, statistical protein identification and quantification, and dissemination of the results. The integrated workflow combines three software tools: mProphet for peptide identification via probabilistic scoring; SRMstats for protein significance analysis with linear mixed-effect models; and PASSEL, a public repository for storage, retrieval and query of SRM data. The input requirements for the protocol are files with SRM traces in mzXML format, and a file with a list of transitions in a text tab-separated format. The protocol is especially suited for data with heavy isotope-labeled peptide internal standards. We demonstrate the protocol on a clinical data set in which the abundances of 35 biomarker candidates were profiled in 83 blood plasma samples of subjects with ovarian cancer or benign ovarian tumors. The time frame to realize the protocol is 1-2 weeks, depending on the number of replicates used in the experiment.

  14. Target Fortification of Breast Milk: How Often Should Milk Analysis Be Done?

    Directory of Open Access Journals (Sweden)

    Niels Rochow

    2015-04-01

    Full Text Available Target fortification (TFO reduces natural macronutrient variation in breast milk (BM. Daily BM analysis for TFO increases neonatal intensive care unit work load by 10–15 min/patient/day and may not be feasible in all nurseries. The variation of macronutrient intake when BM analysis is done for various schedules was studied. In an observational study, we analyzed 21 subsequent samples of native 24-h BM batches, which had been prepared for 10 healthy infants (gestational age 26.1 ± 1.3 weeks, birth weight: 890 ± 210 g. Levels of protein and fat (validated near-infrared milk analyzer, as well as lactose (UPLC-MS/MS generated the database for modelling TFO to meet recommendations of European Society for Paediatric Gastroenterology Hepatology and Nutrition. Intake of macronutrients and energy were calculated for different schedules of BM measurements for TFO (n = 1/week; n = 2/week; n = 3/week; n = 5/week; n = 7/week and compared to native and fixed dose fortified BM. Day-to-day variation of macronutrients (protein 20%, carbohydrate 13%, fat 17%, energy 10% decreased as the frequency of milk analysis increased and was almost zero for protein and carbohydrate with daily measurements. Measurements two/week led to mean macronutrient intake within a range of ±5% of targeted levels. A reduced schedule for macronutrient measurement may increase the practical use of TFO. To what extent the day-to-day variation affects growth while mean intake is stable needs to be studied.

  15. Motion state analysis of space target based on optical cross section

    Science.gov (United States)

    Tian, Qichen; Li, Zhi; Xu, Can; Liu, Chenghao

    2017-10-01

    In order to solve the problem that the movement state analysis method of the space target based on OCS is not related to the real motion state. This paper proposes a method based on OCS for analyzing the state of space target motion. This paper first establish a three-dimensional model of real STSS satellite, then change the satellite's surface into element, and assign material to each panel according to the actual conditions of the satellite. This paper set up a motion scene according to the orbit parameters of STSS satellite in STK, and the motion states are set to three axis steady state and slowly rotating unstable state respectively. In these two states, the occlusion condition of the surface element is firstly determined, and the effective face element is selected. Then, the coordinates of the observation station and the solar coordinates in the satellite body coordinate system are input into the OCS calculation program, and the OCS variation curves of the three axis steady state and the slow rotating unstable state STSS satellite are obtained. Combining the satellite surface structure and the load situation, the OCS change curve of the three axis stabilized satellite is analyzed, and the conclude that the OCS curve fluctuates up and down when the sunlight is irradiated to the load area; By using Spectral analysis method, autocorrelation analysis and the cross residual method, the rotation speed of OCS satellite in slow rotating unstable state is analyzed, and the rotation speed of satellite is successfully reversed. By comparing the three methods, it is found that the cross residual method is more accurate.

  16. The drug-minded protein interaction database (DrumPID) for efficient target analysis and drug development.

    Science.gov (United States)

    Kunz, Meik; Liang, Chunguang; Nilla, Santosh; Cecil, Alexander; Dandekar, Thomas

    2016-01-01

    The drug-minded protein interaction database (DrumPID) has been designed to provide fast, tailored information on drugs and their protein networks including indications, protein targets and side-targets. Starting queries include compound, target and protein interactions and organism-specific protein families. Furthermore, drug name, chemical structures and their SMILES notation, affected proteins (potential drug targets), organisms as well as diseases can be queried including various combinations and refinement of searches. Drugs and protein interactions are analyzed in detail with reference to protein structures and catalytic domains, related compound structures as well as potential targets in other organisms. DrumPID considers drug functionality, compound similarity, target structure, interactome analysis and organismic range for a compound, useful for drug development, predicting drug side-effects and structure-activity relationships.Database URL:http://drumpid.bioapps.biozentrum.uni-wuerzburg.de. © The Author(s) 2016. Published by Oxford University Press.

  17. Genome-wide identification of the regulatory targets of a transcription factor using biochemical characterization and computational genomic analysis

    Directory of Open Access Journals (Sweden)

    Jolly Emmitt R

    2005-11-01

    Full Text Available Abstract Background A major challenge in computational genomics is the development of methodologies that allow accurate genome-wide prediction of the regulatory targets of a transcription factor. We present a method for target identification that combines experimental characterization of binding requirements with computational genomic analysis. Results Our method identified potential target genes of the transcription factor Ndt80, a key transcriptional regulator involved in yeast sporulation, using the combined information of binding affinity, positional distribution, and conservation of the binding sites across multiple species. We have also developed a mathematical approach to compute the false positive rate and the total number of targets in the genome based on the multiple selection criteria. Conclusion We have shown that combining biochemical characterization and computational genomic analysis leads to accurate identification of the genome-wide targets of a transcription factor. The method can be extended to other transcription factors and can complement other genomic approaches to transcriptional regulation.

  18. Electro-optic analysis of the influence of target geometry on electromagnetic pulses generated by petawatt laser-matter interactions

    Science.gov (United States)

    Robinson, Timothy; Giltrap, Samuel; Eardley, Samuel; Consoli, Fabrizio; De Angelis, Riccardo; Ingenito, Francesco; Stuart, Nicholas; Verona, Claudio; Smith, Roland A.

    2018-01-01

    We present an analysis of strong laser-driven electromagnetic pulses using novel electro-optic diagnostic techniques. A range of targets were considered, including thin plastic foils (20-550 nm) and mass-limited, optically-levitated micro-targets. Results from foils indicate a dependence of EMP on target thickness, with larger peak electric fields observed with thinner targets. Spectral analysis suggests high repeatability between shots, with identified spectral features consistently detected with earth following ejection of hot electrons from the plasma, in contrast to predictions for pin-mounted foils in the Poyé EMP generation model. With levitated targets, no EMP was measurable above the noise threshold of any diagnostic, despite observation of protons accelerated to >30 MeV energies, suggesting the discharge current contribution to EMP is dominant.

  19. Content analysis of targeted food and beverage advertisements in a Chinese-American neighbourhood.

    Science.gov (United States)

    Bragg, Marie A; Pageot, Yrvane K; Hernández-Villarreal, Olivia; Kaplan, Sue A; Kwon, Simona C

    2017-08-01

    The current descriptive study aimed to: (i) quantify the number and type of advertisements (ads) located in a Chinese-American neighbourhood in a large, urban city; and (ii) catalogue the targeted marketing themes used in the food/beverage ads. Ten pairs of trained research assistants photographed all outdoor ads in a 0·6 mile2 (1·6 km2) area where more than 60·0 % of residents identify as Chinese American. We used content analysis to assess the marketing themes of ads, including references to: Asian cultures; health; various languages; children; food or beverage type (e.g. sugar-sweetened soda). Lower East Side, a neighbourhood located in the borough of Manhattan in New York City, USA. Ads (n 1366) in the designated neighbourhood. Food/beverage ads were the largest ad category (29·7 %, n 407), followed by services (e.g. mobile phone services; 21·0 %, n 288). Sixty-seven per cent (66·9 %) of beverages featured were sugar-sweetened, and 50·8 % of food ads promoted fast food. Fifty-five per cent (54·9 %) of food/beverage ads targeted Asian Americans through language, ethnicity of person(s) in the ad or inclusion of culturally relevant images. Fifty per cent (50·2 %) of ads were associated with local/small brands. Food/beverage marketing practices are known to promote unhealthy food and beverage products. Research shows that increased exposure leads to excessive short-term consumption among consumers and influences children's food preferences and purchase requests. Given the frequency of racially targeted ads for unhealthy products in the current study and increasing rates of obesity-related diseases among Asian Americans, research and policies should address the implications of food and beverage ads on health.

  20. Content analysis of targeted food and beverage advertisements in a Chinese-American neighbourhood

    Science.gov (United States)

    Bragg, Marie A; Pageot, Yrvane K; Hernández-Villarreal, Olivia; Kaplan, Sue A; Kwon, Simona C

    2017-01-01

    Objectives The current descriptive study aimed to: (i) quantify the number and type of advertisements (ads) located in a Chinese-American neighbourhood in a large, urban city; and (ii) catalogue the targeted marketing themes used in the food/beverage ads. Design Ten pairs of trained research assistants photographed all outdoor ads in a 0.6 mile2 (1.6 km2) area where more than 60.0 % of residents identify as Chinese American. We used content analysis to assess the marketing themes of ads, including references to: Asian cultures; health; various languages; children; food or beverage type (e.g. sugar-sweetened soda). Setting Lower East Side, a neighbourhood located in the borough of Manhattan in New York City, USA. Subjects Ads (n 1366) in the designated neighbourhood. Results Food/beverage ads were the largest ad category (29.7 %, n 407), followed by services (e.g. mobile phone services; 21.0 %, n 288). Sixty-seven per cent (66.9 %) of beverages featured were sugar-sweetened, and 50.8 % of food ads promoted fast food. Fifty-five per cent (54.9 %) of food/beverage ads targeted Asian Americans through language, ethnicity of person(s) in the ad or inclusion of culturally relevant images. Fifty per cent (50.2 %) of ads were associated with local/small brands. Conclusions Food/beverage marketing practices are known to promote unhealthy food and beverage products. Research shows that increased exposure leads to excessive short-term consumption among consumers and influences children’s food preferences and purchase requests. Given the frequency of racially targeted ads for unhealthy products in the current study and increasing rates of obesity-related diseases among Asian Americans, research and policies should address the implications of food and beverage ads on health. PMID:28587693

  1. Practical using of TXRF spectrometers with slitless collimators for the trace analysis of targets surfaces

    International Nuclear Information System (INIS)

    Egorov, V.K.; Zuev, A.P.; Kondratiev, O.S.; Egorov, E.V.

    2000-01-01

    TXRF spectrometer with the slitless collimator used for a formation of the x-ray excitating beam (TXRF-SC spectrometer) is a new variety of an instrument been destined for the trace analysis of surfaces by x-ray fluorescence method at the total reflection of the x-ray incident beam. Some theoretical concepts are introduced for a characterization of the x-ray optics been unique to the TXRF-SC spectrometer. The principle design of the TXRF-SC spectrometer used for the trace quantitative analysis of a surface are discussed. Spectra of a secondary x-ray radiation yield for typical targets been collected by using of the TXRF-SC spectrometer and calculation of surface trace elements concentrations are presented. The analytical and operating parameters of the TXRF-SC spectrometer and one characterized by standard optical scheme are compared. The slitless collimator of the x-ray radiation is formed by two quartz polished plates mated together. Lengths of the plates are not equal. The target is placed on the surface of the long quartz plate and produces the continuation of the initial slitless collimator. Target orientation problem vanishes but problem of the surface contact effect appears. The secondary x-ray radiation excitated in a surface of the target is led out across the hole in the long quartz plate. The radiation is registered by a standard Si (Li) semiconductor detector and is collected by a multi-channel analyzer. The fundamental difference of the x-ray optical scheme been unique to TXRF-SC spectrometer from the standard one is the excitation of a studied surface by a flared x-ray beam with angle ΔΘ = 2Θ c , where Θ c is the critical angle of the total reflection. The vital peculiarity of a x-ray slitless collimation is the absence of a radiation monochromatism in output of the collimator. The sensible divergence of the x-ray excitating beam and the availability in it of monochromatic and white radiation alike allow to get in the surface layer of target the

  2. SUMOFLUX: A Generalized Method for Targeted 13C Metabolic Flux Ratio Analysis

    Science.gov (United States)

    Kogadeeva, Maria

    2016-01-01

    Metabolic fluxes are a cornerstone of cellular physiology that emerge from a complex interplay of enzymes, carriers, and nutrients. The experimental assessment of in vivo intracellular fluxes using stable isotopic tracers is essential if we are to understand metabolic function and regulation. Flux estimation based on 13C or 2H labeling relies on complex simulation and iterative fitting; processes that necessitate a level of expertise that ordinarily preclude the non-expert user. To overcome this, we have developed SUMOFLUX, a methodology that is broadly applicable to the targeted analysis of 13C-metabolic fluxes. By combining surrogate modeling and machine learning, we trained a predictor to specialize in estimating flux ratios from measurable 13C-data. SUMOFLUX targets specific flux features individually, which makes it fast, user-friendly, applicable to experimental design and robust in terms of experimental noise and exchange flux magnitude. Collectively, we predict that SUMOFLUX's properties realistically pave the way to high-throughput flux analyses. PMID:27626798

  3. SUPERPIXEL BASED FACTOR ANALYSIS AND TARGET TRANSFORMATION METHOD FOR MARTIAN MINERALS DETECTION

    Directory of Open Access Journals (Sweden)

    X. Wu

    2018-04-01

    Full Text Available The Factor analysis and target transformation (FATT is an effective method to test for the presence of particular mineral on Martian surface. It has been used both in thermal infrared (Thermal Emission Spectrometer, TES and near-infrared (Compact Reconnaissance Imaging Spectrometer for Mars, CRISM hyperspectral data. FATT derived a set of orthogonal eigenvectors from a mixed system and typically selected first 10 eigenvectors to least square fit the library mineral spectra. However, minerals present only in a limited pixels will be ignored because its weak spectral features compared with full image signatures. Here, we proposed a superpixel based FATT method to detect the mineral distributions on Mars. The simple linear iterative clustering (SLIC algorithm was used to partition the CRISM image into multiple connected image regions with spectral homogeneous to enhance the weak signatures by increasing their proportion in a mixed system. A least square fitting was used in target transformation and performed to each region iteratively. Finally, the distribution of the specific minerals in image was obtained, where fitting residual less than a threshold represent presence and otherwise absence. We validate our method by identifying carbonates in a well analysed CRISM image in Nili Fossae on Mars. Our experimental results indicate that the proposed method work well both in simulated and real data sets.

  4. Rapid targeted somatic mutation analysis of solid tumors in routine clinical diagnostics.

    Science.gov (United States)

    Magliacane, Gilda; Grassini, Greta; Bartocci, Paola; Francaviglia, Ilaria; Dal Cin, Elena; Barbieri, Gianluca; Arrigoni, Gianluigi; Pecciarini, Lorenza; Doglioni, Claudio; Cangi, Maria Giulia

    2015-10-13

    Tumor genotyping is an essential step in routine clinical practice and pathology laboratories face a major challenge in being able to provide rapid, sensitive and updated molecular tests. We developed a novel mass spectrometry multiplexed genotyping platform named PentaPanel to concurrently assess single nucleotide polymorphisms in 56 hotspots of the 5 most clinically relevant cancer genes, KRAS, NRAS, BRAF, EGFR and PIK3CA for a total of 221 detectable mutations. To both evaluate and validate the PentaPanel performance, we investigated 1025 tumor specimens of 6 different cancer types (carcinomas of colon, lung, breast, pancreas, and biliary tract, and melanomas), systematically addressing sensitivity, specificity, and reproducibility of our platform. Sanger sequencing was also performed for all the study samples. Our data showed that PentaPanel is a high throughput and robust tool, allowing genotyping for targeted therapy selection of 10 patients in the same run, with a practical turnaround time of 2 working days. Importantly, it was successfully used to interrogate different DNAs isolated from routinely processed specimens (formalin-fixed paraffin embedded, frozen, and cytological samples), covering all the requirements of clinical tests. In conclusion, the PentaPanel platform can provide an immediate, accurate and cost effective multiplex approach for clinically relevant gene mutation analysis in many solid tumors and its utility across many diseases can be particularly relevant in multiple clinical trials, including the new basket trial approach, aiming to identify appropriate targeted drug combination strategies.

  5. Lead-Bismuth Eutectic cooled experimental Accelerator Driven System. Windowless target unit thermal-hydraulic analysis

    International Nuclear Information System (INIS)

    Bianchi, F.; Ferri, R.; Moreau, V.

    2004-01-01

    A main concern related to the peaceful use of nuclear energy is the safe management of nuclear wastes, with particular attention to long-lived fission products. An increasing attention has recently been addressed to transmutation systems (Accelerator Driven System: ADS) able to 'burn' the actinides and some of the long-lived fission products (High-Level Waste: HLW), transforming them in short or medium-lived wastes that may be easier managed and stored in the geological disposal, with the consequent easier acceptability by population. An ADS consists of a subcritical-core coupled with an accelerator by means of a target. This paper deals with the thermal-hydraulic analysis, performed with STAR-CD and RELAP5 codes for the windowless target unit of Lead-Bismuth Eutectic (LBE) cooled experimental ADS (XADS), both to assess its behaviour during operational and accident sequences and to provide input data for the thermal-mechanical analyses. It also reports a description of modifications properly implemented in the codes used for the assessment of this kind of plants. (author)

  6. Doc toxin is a kinase that inactivates elongation factor Tu.

    Science.gov (United States)

    Cruz, Jonathan W; Rothenbacher, Francesca P; Maehigashi, Tatsuya; Lane, William S; Dunham, Christine M; Woychik, Nancy A

    2014-03-14

    The Doc toxin from bacteriophage P1 (of the phd-doc toxin-antitoxin system) has served as a model for the family of Doc toxins, many of which are harbored in the genomes of pathogens. We have shown previously that the mode of action of this toxin is distinct from the majority derived from toxin-antitoxin systems: it does not cleave RNA; in fact P1 Doc expression leads to mRNA stabilization. However, the molecular triggers that lead to translation arrest are not understood. The presence of a Fic domain, albeit slightly altered in length and at the catalytic site, provided a clue to the mechanism of P1 Doc action, as most proteins with this conserved domain inactivate GTPases through addition of an adenylyl group (also referred to as AMPylation). We demonstrated that P1 Doc added a single phosphate group to the essential translation elongation factor and GTPase, elongation factor (EF)-Tu. The phosphorylation site was at a highly conserved threonine, Thr-382, which was blocked when EF-Tu was treated with the antibiotic kirromycin. Therefore, we have established that Fic domain proteins can function as kinases. This distinct enzymatic activity exhibited by P1 Doc also solves the mystery of the degenerate Fic motif unique to the Doc family of toxins. Moreover, we have established that all characterized Fic domain proteins, even those that phosphorylate, target pivotal GTPases for inactivation through a post-translational modification at a single functionally critical acceptor site.

  7. Doc Toxin Is a Kinase That Inactivates Elongation Factor Tu*

    Science.gov (United States)

    Cruz, Jonathan W.; Rothenbacher, Francesca P.; Maehigashi, Tatsuya; Lane, William S.; Dunham, Christine M.; Woychik, Nancy A.

    2014-01-01

    The Doc toxin from bacteriophage P1 (of the phd-doc toxin-antitoxin system) has served as a model for the family of Doc toxins, many of which are harbored in the genomes of pathogens. We have shown previously that the mode of action of this toxin is distinct from the majority derived from toxin-antitoxin systems: it does not cleave RNA; in fact P1 Doc expression leads to mRNA stabilization. However, the molecular triggers that lead to translation arrest are not understood. The presence of a Fic domain, albeit slightly altered in length and at the catalytic site, provided a clue to the mechanism of P1 Doc action, as most proteins with this conserved domain inactivate GTPases through addition of an adenylyl group (also referred to as AMPylation). We demonstrated that P1 Doc added a single phosphate group to the essential translation elongation factor and GTPase, elongation factor (EF)-Tu. The phosphorylation site was at a highly conserved threonine, Thr-382, which was blocked when EF-Tu was treated with the antibiotic kirromycin. Therefore, we have established that Fic domain proteins can function as kinases. This distinct enzymatic activity exhibited by P1 Doc also solves the mystery of the degenerate Fic motif unique to the Doc family of toxins. Moreover, we have established that all characterized Fic domain proteins, even those that phosphorylate, target pivotal GTPases for inactivation through a post-translational modification at a single functionally critical acceptor site. PMID:24448800

  8. Inactivation of Prions and Amyloid Seeds with Hypochlorous Acid.

    Directory of Open Access Journals (Sweden)

    Andrew G Hughson

    2016-09-01

    Full Text Available Hypochlorous acid (HOCl is produced naturally by neutrophils and other cells to kill conventional microbes in vivo. Synthetic preparations containing HOCl can also be effective as microbial disinfectants. Here we have tested whether HOCl can also inactivate prions and other self-propagating protein amyloid seeds. Prions are deadly pathogens that are notoriously difficult to inactivate, and standard microbial disinfection protocols are often inadequate. Recommended treatments for prion decontamination include strongly basic (pH ≥~12 sodium hypochlorite bleach, ≥1 N sodium hydroxide, and/or prolonged autoclaving. These treatments are damaging and/or unsuitable for many clinical, agricultural and environmental applications. We have tested the anti-prion activity of a weakly acidic aqueous formulation of HOCl (BrioHOCl that poses no apparent hazard to either users or many surfaces. For example, BrioHOCl can be applied directly to skin and mucous membranes and has been aerosolized to treat entire rooms without apparent deleterious effects. Here, we demonstrate that immersion in BrioHOCl can inactivate not only a range of target microbes, including spores of Bacillus subtilis, but also prions in tissue suspensions and on stainless steel. Real-time quaking-induced conversion (RT-QuIC assays showed that BrioHOCl treatments eliminated all detectable prion seeding activity of human Creutzfeldt-Jakob disease, bovine spongiform encephalopathy, cervine chronic wasting disease, sheep scrapie and hamster scrapie; these findings indicated reductions of ≥103- to 106-fold. Transgenic mouse bioassays showed that all detectable hamster-adapted scrapie infectivity in brain homogenates or on steel wires was eliminated, representing reductions of ≥~105.75-fold and >104-fold, respectively. Inactivation of RT-QuIC seeding activity correlated with free chlorine concentration and higher order aggregation or destruction of proteins generally, including prion

  9. Specter: linear deconvolution for targeted analysis of data-independent acquisition mass spectrometry proteomics.

    Science.gov (United States)

    Peckner, Ryan; Myers, Samuel A; Jacome, Alvaro Sebastian Vaca; Egertson, Jarrett D; Abelin, Jennifer G; MacCoss, Michael J; Carr, Steven A; Jaffe, Jacob D

    2018-05-01

    Mass spectrometry with data-independent acquisition (DIA) is a promising method to improve the comprehensiveness and reproducibility of targeted and discovery proteomics, in theory by systematically measuring all peptide precursors in a biological sample. However, the analytical challenges involved in discriminating between peptides with similar sequences in convoluted spectra have limited its applicability in important cases, such as the detection of single-nucleotide polymorphisms (SNPs) and alternative site localizations in phosphoproteomics data. We report Specter (https://github.com/rpeckner-broad/Specter), an open-source software tool that uses linear algebra to deconvolute DIA mixture spectra directly through comparison to a spectral library, thus circumventing the problems associated with typical fragment-correlation-based approaches. We validate the sensitivity of Specter and its performance relative to that of other methods, and show that Specter is able to successfully analyze cases involving highly similar peptides that are typically challenging for DIA analysis methods.

  10. Preliminary shielding analysis in support of the CSNS target station shutter neutron beam stop design

    Institute of Scientific and Technical Information of China (English)

    ZHANG Bin; CHEN Yi-Xue; WANG Wei-Jin; YANG Shou-Hai; WU Jun; YIN Wen; LIANG Tian-Jiao; JIA Xue-Jun

    2011-01-01

    The construction of China Spallation Neutron Source (CSNS) has been initiated in Dongguan,Guangdong, China.Thus a detailed radiation transport analysis of the shutter neutron beam stop is of vital importance. The analyses are performed using the coupled Monte Carlo and multi-dimensional discrete ordinates method. The target of calculations is to optimize the neutron beamline shielding design to guarantee personal safety and minimize cost. Successful elimination of the primary ray effects via the two-dimensional uncollided flux and the first collision source methodology is also illustrated. Two-dimensional dose distribution is calculated. The dose at the end of the neutron beam line is less than 2.5μSv/h. The models have ensured that the doses received by the hall staff members are below the standard limit required.

  11. Thick-target Pixe analysis of chromium, copper and arsenic impregnated lumber

    International Nuclear Information System (INIS)

    Saarela, K-E.; Harju, L.; Lill, J-O.; Rajander, J.; Lindroos, A.; Heselius, S-J.

    1999-01-01

    Chromium, copper and arsenic (CCA) have for decades been used for wood preservation. Of these elements especially arsenic is very toxic. As CCA impregnated wood is still today used for many construction purposes, a monitoring of these metal ions is of great environmental importance. Thick-target PIXE is a powerful method for the determination of trace metals in wood. The TTPIXE method enabled study of variations of the elemental concentrations in lumber treated with CCA impregnation solution. Distribution patterns were obtained for both naturally occurring elements and elements introduced in the treatment process. During the impregnation process a desorption of e.g. alkali metal ions takes place from the wood. The sensitivity of the method is improved by dry ashing of the samples prior to PIXE analysis. The TTPIXE method was calibrated and validated using international certified reference materials (CRM) based on wood material

  12. Integrated analysis of the molecular action of Vorinostat identifies epi-sensitised targets for combination therapy.

    Science.gov (United States)

    Hay, Jodie F; Lappin, Katrina; Liberante, Fabio; Kettyle, Laura M; Matchett, Kyle B; Thompson, Alexander; Mills, Ken I

    2017-09-15

    Several histone deacetylase inhibitors including Vorinostat have received FDA approval for the treatment of haematological malignancies. However, data from these trials indicate that Vorinostat has limited efficacy as a monotherapy, prompting the need for rational design of combination therapies. A number of epi-sensitised pathways, including sonic hedgehog (SHH), were identified in AML cells by integration of global patterns of histone H3 lysine 9 (H3K9) acetylation with transcriptomic analysis following Vorinostat-treatment. Direct targeting of the SHH pathway with SANT-1, following Vorinostat induced epi-sensitisation, resulted in synergistic cell death of AML cells. In addition, xenograft studies demonstrated that combination therapy induced a marked reduction in leukemic burden compared to control or single agents. Together, the data supports epi-sensitisation as a potential component of the strategy for the rational development of combination therapies in AML.

  13. GAMUT: GPU accelerated microRNA analysis to uncover target genes through CUDA-miRanda

    Science.gov (United States)

    2014-01-01

    Background Non-coding sequences such as microRNAs have important roles in disease processes. Computational microRNA target identification (CMTI) is becoming increasingly important since traditional experimental methods for target identification pose many difficulties. These methods are time-consuming, costly, and often need guidance from computational methods to narrow down candidate genes anyway. However, most CMTI methods are computationally demanding, since they need to handle not only several million query microRNA and reference RNA pairs, but also several million nucleotide comparisons within each given pair. Thus, the need to perform microRNA identification at such large scale has increased the demand for parallel computing. Methods Although most CMTI programs (e.g., the miRanda algorithm) are based on a modified Smith-Waterman (SW) algorithm, the existing parallel SW implementations (e.g., CUDASW++ 2.0/3.0, SWIPE) are unable to meet this demand in CMTI tasks. We present CUDA-miRanda, a fast microRNA target identification algorithm that takes advantage of massively parallel computing on Graphics Processing Units (GPU) using NVIDIA's Compute Unified Device Architecture (CUDA). CUDA-miRanda specifically focuses on the local alignment of short (i.e., ≤ 32 nucleotides) sequences against longer reference sequences (e.g., 20K nucleotides). Moreover, the proposed algorithm is able to report multiple alignments (up to 191 top scores) and the corresponding traceback sequences for any given (query sequence, reference sequence) pair. Results Speeds over 5.36 Giga Cell Updates Per Second (GCUPs) are achieved on a server with 4 NVIDIA Tesla M2090 GPUs. Compared to the original miRanda algorithm, which is evaluated on an Intel Xeon E5620@2.4 GHz CPU, the experimental results show up to 166 times performance gains in terms of execution time. In addition, we have verified that the exact same targets were predicted in both CUDA-miRanda and the original mi

  14. Identification of estrogen target genes during zebrafish embryonic development through transcriptomic analysis.

    Directory of Open Access Journals (Sweden)

    Ruixin Hao

    Full Text Available Estrogen signaling is important for vertebrate embryonic development. Here we have used zebrafish (Danio rerio as a vertebrate model to analyze estrogen signaling during development. Zebrafish embryos were exposed to 1 µM 17β-estradiol (E2 or vehicle from 3 hours to 4 days post fertilization (dpf, harvested at 1, 2, 3 and 4 dpf, and subjected to RNA extraction for transcriptome analysis using microarrays. Differentially expressed genes by E2-treatment were analyzed with hierarchical clustering followed by biological process and tissue enrichment analysis. Markedly distinct sets of genes were up and down-regulated by E2 at the four different time points. Among these genes, only the well-known estrogenic marker vtg1 was co-regulated at all time points. Despite this, the biological functional categories targeted by E2 were relatively similar throughout zebrafish development. According to knowledge-based tissue enrichment, estrogen responsive genes were clustered mainly in the liver, pancreas and brain. This was in line with the developmental dynamics of estrogen-target tissues that were visualized using transgenic zebrafish containing estrogen responsive elements driving the expression of GFP (Tg(5xERE:GFP. Finally, the identified embryonic estrogen-responsive genes were compared to already published estrogen-responsive genes identified in male adult zebrafish (Gene Expression Omnibus database. The expressions of a few genes were co-regulated by E2 in both embryonic and adult zebrafish. These could potentially be used as estrogenic biomarkers for exposure to estrogens or estrogenic endocrine disruptors in zebrafish. In conclusion, our data suggests that estrogen effects on early embryonic zebrafish development are stage- and tissue- specific.

  15. Genome-wide analysis of PDX1 target genes in human pancreatic progenitors

    Directory of Open Access Journals (Sweden)

    Xianming Wang

    2018-03-01

    Full Text Available Objective: Homozygous loss-of-function mutations in the gene coding for the homeobox transcription factor (TF PDX1 leads to pancreatic agenesis, whereas heterozygous mutations can cause Maturity-Onset Diabetes of the Young 4 (MODY4. Although the function of Pdx1 is well studied in pre-clinical models during insulin-producing β-cell development and homeostasis, it remains elusive how this TF controls human pancreas development by regulating a downstream transcriptional program. Also, comparative studies of PDX1 binding patterns in pancreatic progenitors and adult β-cells have not been conducted so far. Furthermore, many studies reported the association between single nucleotide polymorphisms (SNPs and T2DM, and it has been shown that islet enhancers are enriched in T2DM-associated SNPs. Whether regions, harboring T2DM-associated SNPs are PDX1 bound and active at the pancreatic progenitor stage has not been reported so far. Methods: In this study, we have generated a novel induced pluripotent stem cell (iPSC line that efficiently differentiates into human pancreatic progenitors (PPs. Furthermore, PDX1 and H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq was used to identify PDX1 transcriptional targets and active enhancer and promoter regions. To address potential differences in the function of PDX1 during development and adulthood, we compared PDX1 binding profiles from PPs and adult islets. Moreover, combining ChIP-seq and GWAS meta-analysis data we identified T2DM-associated SNPs in PDX1 binding sites and active chromatin regions. Results: ChIP-seq for PDX1 revealed a total of 8088 PDX1-bound regions that map to 5664 genes in iPSC-derived PPs. The PDX1 target regions include important pancreatic TFs, such as PDX1 itself, RFX6, HNF1B, and MEIS1, which were activated during the differentiation process as revealed by the active chromatin mark H3K27ac and mRNA expression profiling, suggesting that auto-regulatory feedback regulation

  16. Multivariate analysis for the estimation of target localization errors in fiducial marker-based radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Takamiya, Masanori [Department of Nuclear Engineering, Graduate School of Engineering, Kyoto University, Kyoto 606-8501, Japan and Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Nakamura, Mitsuhiro, E-mail: m-nkmr@kuhp.kyoto-u.ac.jp; Akimoto, Mami; Ueki, Nami; Yamada, Masahiro; Matsuo, Yukinori; Mizowaki, Takashi; Hiraoka, Masahiro [Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Tanabe, Hiroaki [Division of Radiation Oncology, Institute of Biomedical Research and Innovation, Kobe 650-0047 (Japan); Kokubo, Masaki [Division of Radiation Oncology, Institute of Biomedical Research and Innovation, Kobe 650-0047, Japan and Department of Radiation Oncology, Kobe City Medical Center General Hospital, Kobe 650-0047 (Japan); Itoh, Akio [Department of Nuclear Engineering, Graduate School of Engineering, Kyoto University, Kyoto 606-8501 (Japan)

    2016-04-15

    Purpose: To assess the target localization error (TLE) in terms of the distance between the target and the localization point estimated from the surrogates (|TMD|), the average of respiratory motion for the surrogates and the target (|aRM|), and the number of fiducial markers used for estimating the target (n). Methods: This study enrolled 17 lung cancer patients who subsequently underwent four fractions of real-time tumor tracking irradiation. Four or five fiducial markers were implanted around the lung tumor. The three-dimensional (3D) distance between the tumor and markers was at maximum 58.7 mm. One of the markers was used as the target (P{sub t}), and those markers with a 3D |TMD{sub n}| ≤ 58.7 mm at end-exhalation were then selected. The estimated target position (P{sub e}) was calculated from a localization point consisting of one to three markers except P{sub t}. Respiratory motion for P{sub t} and P{sub e} was defined as the root mean square of each displacement, and |aRM| was calculated from the mean value. TLE was defined as the root mean square of each difference between P{sub t} and P{sub e} during the monitoring of each fraction. These procedures were performed repeatedly using the remaining markers. To provide the best guidance on the answer with n and |TMD|, fiducial markers with a 3D |aRM ≥ 10 mm were selected. Finally, a total of 205, 282, and 76 TLEs that fulfilled the 3D |TMD| and 3D |aRM| criteria were obtained for n = 1, 2, and 3, respectively. Multiple regression analysis (MRA) was used to evaluate TLE as a function of |TMD| and |aRM| in each n. Results: |TMD| for n = 1 was larger than that for n = 3. Moreover, |aRM| was almost constant for all n, indicating a similar scale for the marker’s motion near the lung tumor. MRA showed that |aRM| in the left–right direction was the major cause of TLE; however, the contribution made little difference to the 3D TLE because of the small amount of motion in the left–right direction. The TLE

  17. High Pressure Inactivation of HAV within Mussels

    Science.gov (United States)

    The potential of hepatitis A virus (HAV) to be inactivated within Mediterranean mussels (Mytilus galloprovincialis) and blue mussels (Mytilus edulis) by high pressure processing was evaluated. HAV was bioaccumulated within mussels to approximately 6-log10 PFU by exposure of mussels to HAV-contamina...

  18. Inactivation of prion infectivity by ionizing rays

    Energy Technology Data Exchange (ETDEWEB)

    Gominet, M. [Ionisos, ZI les Chatinieres, F01120 Dagneux (France); Vadrot, C.; Austruy, G. [Paris V University, Central Pharmacy of Hospitals, 4 avenue de l' Observatoire, F-75006, Paris (France); Darbord, J.C. [Paris V University, Central Pharmacy of Hospitals, 4 avenue de l' Observatoire, F-75006, Paris (France)], E-mail: darbord@pharmacie.univ-paris5.fr

    2007-11-15

    Inactivation of prion deposits on medical devices or prion contamination in pharmaceutical raw materials is considered as impossible by using gamma irradiation. Early, the guideline WHO/CDS/CSR/APH/2000 has described irradiation as an ineffective process. But, in 2003, S. Miekka et al. noted radiation inactivation of prions in a particular application to purify human albumin, shown by the physical denaturation of the infectious protein (PrP). The aim of our study was to determine the inactivation of prions with a scrapie model (strain C506M3) by irradiating standardised preparations. Results: Gamma irradiation was partially effective, showing a 4-5 log reduction on exposure to 50 kGy. A characteristic effect-dose curve was not observed (25, 50 and 100 kGy), only an increase in the incubation period of the murine disease (229 days with 25 kGy to 290 days with 100 kGy) compared with 170 days without irradiation. Since the inactivation was not a total one, the observed effect is significant. It is proposed that further work be undertaken with the model to investigate the application of gamma radiation known levels of prion contamination.

  19. Inactivation of prion infectivity by ionizing rays

    International Nuclear Information System (INIS)

    Gominet, M.; Vadrot, C.; Austruy, G.; Darbord, J.C.

    2007-01-01

    Inactivation of prion deposits on medical devices or prion contamination in pharmaceutical raw materials is considered as impossible by using gamma irradiation. Early, the guideline WHO/CDS/CSR/APH/2000 has described irradiation as an ineffective process. But, in 2003, S. Miekka et al. noted radiation inactivation of prions in a particular application to purify human albumin, shown by the physical denaturation of the infectious protein (PrP). The aim of our study was to determine the inactivation of prions with a scrapie model (strain C506M3) by irradiating standardised preparations. Results: Gamma irradiation was partially effective, showing a 4-5 log reduction on exposure to 50 kGy. A characteristic effect-dose curve was not observed (25, 50 and 100 kGy), only an increase in the incubation period of the murine disease (229 days with 25 kGy to 290 days with 100 kGy) compared with 170 days without irradiation. Since the inactivation was not a total one, the observed effect is significant. It is proposed that further work be undertaken with the model to investigate the application of gamma radiation known levels of prion contamination

  20. Pulsed electric field inactivation in a microreactor

    NARCIS (Netherlands)

    Fox, M.B.

    2006-01-01

    Pulsed electric fields (PEF) is a novel, non-thermal pasteurization method which uses short, high electric field pulses to inactivate microorganisms. The advantage of a pasteurization method like PEF compared to regular heat pasteurization is that the taste, flavour, texture and nutritional value

  1. Epigenetic inactivation of CHFR in human tumors.

    Science.gov (United States)

    Toyota, Minoru; Sasaki, Yasushi; Satoh, Ayumi; Ogi, Kazuhiro; Kikuchi, Takefumi; Suzuki, Hiromu; Mita, Hiroaki; Tanaka, Nobuyuki; Itoh, Fumio; Issa, Jean-Pierre J; Jair, Kam-Wing; Schuebel, Kornel E; Imai, Kohzoh; Tokino, Takashi

    2003-06-24

    Cell-cycle checkpoints controlling the orderly progression through mitosis are frequently disrupted in human cancers. One such checkpoint, entry into metaphase, is regulated by the CHFR gene encoding a protein possessing forkhead-associated and RING finger domains as well as ubiquitin-ligase activity. Although defects in this checkpoint have been described, the molecular basis and prevalence of CHFR inactivation in human tumors are still not fully understood. To address this question, we analyzed the pattern of CHFR expression in a number of human cancer cell lines and primary tumors. We found CpG methylation-dependent silencing of CHFR expression in 45% of cancer cell lines, 40% of primary colorectal cancers, 53% of colorectal adenomas, and 30% of primary head and neck cancers. Expression of CHFR was precisely correlated with both CpG methylation and deacetylation of histones H3 and H4 in the CpG-rich regulatory region. Moreover, CpG methylation and thus silencing of CHFR depended on the activities of two DNA methyltransferases, DNMT1 and DNMT3b, as their genetic inactivation restored CHFR expression. Finally, cells with CHFR methylation had an intrinsically high mitotic index when treated with microtubule inhibitor. This means that cells in which CHFR was epigenetically inactivated constitute loss-of-function alleles for mitotic checkpoint control. Taken together, these findings shed light on a pathway by which mitotic checkpoint is bypassed in cancer cells and suggest that inactivation of checkpoint genes is much more widespread than previously suspected.

  2. Space-based infrared sensors of space target imaging effect analysis

    Science.gov (United States)

    Dai, Huayu; Zhang, Yasheng; Zhou, Haijun; Zhao, Shuang

    2018-02-01

    Target identification problem is one of the core problem of ballistic missile defense system, infrared imaging simulation is an important means of target detection and recognition. This paper first established the space-based infrared sensors ballistic target imaging model of point source on the planet's atmosphere; then from two aspects of space-based sensors camera parameters and target characteristics simulated atmosphere ballistic target of infrared imaging effect, analyzed the camera line of sight jitter, camera system noise and different imaging effects of wave on the target.

  3. Expression and activity analysis of a new fusion protein targeting ovarian cancer cells.

    Science.gov (United States)

    Su, Manman; Chang, Weiqin; Wang, Dingding; Cui, Manhua; Lin, Yang; Wu, Shuying; Xu, Tianmin

    2015-09-01

    The aim of the present study was to develop a new therapeutic drug to improve the prognosis of ovarian cancer patients. Human urokinase-type plasminogen activator (uPA)17-34-kunitz-type protease inhibitor (KPI) eukaryotic expression vector was constructed and recombinant human uPA17-34-KPI (rhuPA17-34-KPI) in P. pastoris was expressed. In the present study, the DNA sequences that encode uPA 17-34 amino acids were created according to the native amino acids sequence and inserted into the KPI-pPICZαC vector, which was constructed. Then, uPA17‑34-KPI-pPICZαC was transformed into P. pastoris X-33, and rhuPA17-34-KPI was expressed by induction of methanol. The bioactivities of a recombinant fusion protein were detected with trypsin inhibition analysis, and the inhibitory effects on the growth of ovarian cancer cells were identified using the TUNEL assay, in vitro wound‑healing assay and Matrigel model analysis. The results of the DNA sequence analysis of the recombinant vector uPA17-34-KPI‑pPICZα demonstrated that the DNA‑encoding human uPA 17-34 amino acids, 285-288 amino acids of amyloid precursor protein (APP) and 1-57 amino acids of KPI were correctly inserted into the pPICZαC vector. Following induction by methonal, the fusion protein with a molecular weight of 8.8 kDa was observed using SDS-PAGE and western blot analysis. RhuPA17-34-KPI was expressed in P. pastoris with a yield of 50 mg/l in a 50-ml tube. The recombinant fusion protein was able to inhibit the activity of trypsin, inhibit growth and induce apoptosis of SKOV3 cells, and inhibit the invasion and metastasis of ovarian cancer cells. By considering uPA17-34 amino acid specific binding uPAR as the targeted part of fusion protein and utilizing the serine protease inhibitor activity of KPI, it was found that the recombinant fusion protein uPA17-34-KPI inhibited the invasion and metastasis of ovarian tumors, and may therefore be regarded as effective in targeted treatment.

  4. Cortical inactivation by cooling in small animals

    Directory of Open Access Journals (Sweden)

    Ben eCoomber

    2011-06-01

    Full Text Available Reversible inactivation of the cortex by surface cooling is a powerful method for studying the function of a particular area. Implanted cooling cryoloops have been used to study the role of individual cortical areas in auditory processing of awake-behaving cats. Cryoloops have also been used in rodents for reversible inactivation of the cortex, but recently there has been a concern that the cryoloop may also cool non-cortical structures either directly or via the perfusion of blood, cooled as it passed close to the cooling loop. In this study we have confirmed that the loop can inactivate most of the auditory cortex without causing a significant reduction in temperature of the auditory thalamus or other sub-cortical structures. We placed a cryoloop on the surface of the guinea pig cortex, cooled it to 2°C and measured thermal gradients across the neocortical surface. We found that the temperature dropped to 20-24°C among cells within a radius of about 2.5mm away from the loop. This temperature drop was sufficient to reduce activity of most cortical cells and led to the inactivation of almost the entire auditory region. When the temperature of thalamus, midbrain, and middle ear were measured directly during cortical cooling, there was a small drop in temperature (about 4°C but this was not sufficient to directly reduce neural activity. In an effort to visualise the extent of neural inactivation we measured the uptake of thallium ions following an intravenous injection. This confirmed that there was a large reduction of activity across much of the ipsilateral cortex and only a small reduction in subcortical structures.

  5. Synergistic inactivation of anaerobic wastewater biofilm by free nitrous acid and hydrogen peroxide

    International Nuclear Information System (INIS)

    Jiang, Guangming; Yuan, Zhiguo

    2013-01-01

    Highlights: ► H 2 O 2 greatly enhances the inactivation of microorganisms in biofilms by FNA. ► About 2-log of inactivation of biofilm microbes was achieved by FNA + H 2 O 2 . ► FNA + H 2 O 2 reduced sulfide production and detached biofilm in reactors. -- Abstract: Free nitrous acid (FNA) was recently revealed to be a strong biocide for microbes in anaerobic biofilm, achieving approximately 1-log (90%) inactivation at a concentration of 0.2–0.3 mgHNO 2 -N/L with an exposure time longer than 6 h. The combined biocidal effects of FNA and hydrogen peroxide (H 2 O 2 ) on anaerobic wastewater biofilm are investigated in this study. H 2 O 2 greatly enhances the inactivation of microorganisms by FNA. About 2-log (99%) of microbial inactivation was achieved when biofilms were exposed to FNA at 0.2 mgN/L or above and H 2 O 2 at 30 mg/L or above for 6 h or longer. It was found, through response surface methodology and ridge analysis, that FNA is the primary inactivation agent and H 2 O 2 enhances its efficiency. The loss and the subsequent slow recovery of biological activity in biofilm reactors subjected to FNA and H 2 O 2 dosing confirmed that the chemical combination could achieve higher microbial inactivation than with FNA alone. Reaction simulation shows that intermediates of reactions between FNA and H 2 O 2 , like peroxynitrite and nitrogen dioxide, would be produced at elevated levels and are likely responsible for the synergism between FNA and H 2 O 2 . The combination of FNA and H 2 O 2 could potentially provide an effective solution to sewer biofilm control

  6. Radar cross-section (RCS) analysis of high frequency surface wave radar targets

    OpenAIRE

    ÇAKIR, Gonca; SEVGİ, Levent

    2010-01-01

    Realistic high frequency surface wave radar (HFSWR) targets are investigated numerically in terms of electromagnetic wave -- target interactions. Radar cross sections (RCS) of these targets are simulated via both the finite-difference time-domain (FDTD) method and the Method of Moments (MoM). The virtual RCS prediction tool that was introduced in previous work is used for these investigations. The virtual tool automatically creates the discrete FDTD model of the target under investi...

  7. Retro-Techno-Economic Analysis: Using (Bio)Process Systems Engineering Tools to Attain Process Target Values

    DEFF Research Database (Denmark)

    Furlan, Felipe F.; Costa, Caliane B B; Secchi, Argimiro R.

    2016-01-01

    Economic analysis, allied to process systems engineering tools, can provide useful insights about process techno-economic feasibility. More interestingly, rather than being used to evaluate specific process conditions, this techno-economic analysis can be turned upside down to achieve target valu...

  8. Calmodulin-activated cyclic nucleotide phosphodiesterase from brain. Relationship of subunit structure to activity assessed by radiation inactivation

    International Nuclear Information System (INIS)

    Kincaid, R.L.; Kemdner, E.; Manganiello, V.C.; Osborne, J.C.; Vaughan, M.

    1981-01-01

    The apparent target sizes of the basal and calmodulin-dependent activities of calmodulin-activated phosphodiesterase from bovine brain were estimated using target theory analysis of data from radiation inactivation experiments. Whether crude or highly purified samples were irradiated, the following results were obtained. Low doses of radiation caused a 10 to 15% increase in basal activity, which, with further irradiation, decayed with an apparent target size of approx.60,000 daltons. Calmodulin-dependent activity decayed with an apparent target size of approx.105,000 daltons. The percentage stimulation of enzyme activity by calmodulin decreased markedly as a function of radiation dosage. These observations are consistent with results predicted by computer-assisted modeling based on the assumptions that: 1) the calmodulin-activated phosphodiesterase exists as a mixture of monomers which are fully active in the absence of calmodulin and dimers which are inactive in the absence of calmodulin; 2) in the presence of calmodulin, a dimer exhibits activity equal to that of two monomers; 3) on radiation destruction of a dimer, an active monomer is generated. This monomer-dimer hypothesis provides a plausible explanation for and definition of basal and calmodulin-dependent phosphodiesterase activity

  9. Inactivation of Byssochlamys nivea ascospores in strawberry puree by high pressure, power ultrasound and thermal processing.

    Science.gov (United States)

    Evelyn; Silva, F V M

    2015-12-02

    Byssochlamys nivea is a mold that can spoil processed fruit products and produce mycotoxins. In this work, high pressure processing (HPP, 600 MPa) and power ultrasound (24 kHz, 0.33 W/mL; TS) in combination with 75°C for the inactivation of four week old B. nivea ascospores in strawberry puree for up to 30 min was investigated and compared with 75°C thermal processing alone. TS and thermal processing can activate the mold ascospores, but HPP-75°C resulted in 2.0 log reductions after a 20 min process. For a 10 min process, HPP-75°C was better than 85°C alone in reducing B. nivea spores (1.4 vs. 0.2 log reduction), demonstrating that a lower temperature in combination with HPP is more effective for spore inactivation than heat alone at a higher temperature. The ascospore inactivation by HPP-thermal, TS and thermal processing was studied at different temperatures and modeled. Faster inactivation was achieved at higher temperatures for all the technologies tested, indicating the significant role of temperature in spore inactivation, alone or combined with other physical processes. The Weibull model described the spore inactivation by 600 MPa HPP-thermal (38, 50, 60, 75°C) and thermal (85, 90°C) processing, whereas the Lorentzian model was more appropriate for TS treatment (65, 70, 75°C). The models obtained provide a useful tool to design and predict pasteurization processes targeting B. nivea ascospores. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Targeted next-generation sequencing analysis identifies novel mutations in families with severe familial exudative vitreoretinopathy

    Science.gov (United States)

    Huang, Xiao-Yan; Zhuang, Hong; Wu, Ji-Hong; Li, Jian-Kang; Hu, Fang-Yuan; Zheng, Yu; Tellier, Laurent Christian Asker M.; Zhang, Sheng-Hai; Gao, Feng-Juan; Zhang, Jian-Guo

    2017-01-01

    Purpose Familial exudative vitreoretinopathy (FEVR) is a genetically and clinically heterogeneous disease, characterized by failure of vascular development of the peripheral retina. The symptoms of FEVR vary widely among patients in the same family, and even between the two eyes of a given patient. This study was designed to identify the genetic defect in a patient cohort of ten Chinese families with a definitive diagnosis of FEVR. Methods To identify the causative gene, next-generation sequencing (NGS)-based target capture sequencing was performed. Segregation analysis of the candidate variant was performed in additional family members by using Sanger sequencing and quantitative real-time PCR (QPCR). Results Of the cohort of ten FEVR families, six pathogenic variants were identified, including four novel and two known heterozygous mutations. Of the variants identified, four were missense variants, and two were novel heterozygous deletion mutations [LRP5, c.4053 DelC (p.Ile1351IlefsX88); TSPAN12, EX8Del]. The two novel heterozygous deletion mutations were not observed in the control subjects and could give rise to a relatively severe FEVR phenotype, which could be explained by the protein function prediction. Conclusions We identified two novel heterozygous deletion mutations [LRP5, c.4053 DelC (p.Ile1351IlefsX88); TSPAN12, EX8Del] using targeted NGS as a causative mutation for FEVR. These genetic deletion variations exhibit a severe form of FEVR, with tractional retinal detachments compared with other known point mutations. The data further enrich the mutation spectrum of FEVR and enhance our understanding of genotype–phenotype correlations to provide useful information for disease diagnosis, prognosis, and effective genetic counseling. PMID:28867931

  11. Gene Inactivation by CRISPR-Cas9 in Nicotiana tabacum BY-2 Suspension Cells.

    Science.gov (United States)

    Mercx, Sébastien; Tollet, Jérémie; Magy, Bertrand; Navarre, Catherine; Boutry, Marc

    2016-01-01

    Plant suspension cells are interesting hosts for the heterologous production of pharmacological proteins such as antibodies. They have the advantage to facilitate the containment and the application of good manufacturing practices. Furthermore, antibodies can be secreted to the extracellular medium, which makes the purification steps much simpler. However, improvements are still to be made regarding the quality and the production yield. For instance, the inactivation of proteases and the humanization of glycosylation are both important targets which require either gene silencing or gene inactivation. To this purpose, CRISPR-Cas9 is a very promising technique which has been used recently in a series of plant species, but not yet in plant suspension cells. Here, we sought to use the CRISPR-Cas9 system for gene inactivation in Nicotiana tabacum BY-2 suspension cells. We transformed a transgenic line expressing a red fluorescent protein (mCherry) with a binary vector containing genes coding for Cas9 and three guide RNAs targeting mCherry restriction sites, as well as a bialaphos-resistant (bar) gene for selection. To demonstrate gene inactivation in the transgenic lines, the mCherry gene was PCR-amplified and analyzed by electrophoresis. Seven out of 20 transformants displayed a shortened fragment, indicating that a deletion occurred between two target sites. We also analyzed the transformants by restriction fragment length polymorphism and observed that the three targeted restriction sites were hit. DNA sequencing of the PCR fragments confirmed either deletion between two target sites or single nucleotide deletion. We therefore conclude that CRISPR-Cas9 can be used in N. tabacum BY2 cells.

  12. Statistical analysis of target motion in gated lung stereotactic body radiation therapy

    International Nuclear Information System (INIS)

    Zhao Bo; Yang Yong; Li Tianfang; Li Xiang; Heron, Dwight E; Huq, M Saiful

    2011-01-01

    An external surrogate-based respiratory gating technique is a useful method to reduce target margins for the treatment of a moving lung tumor. The success of this technique relies on a good correlation between the motion of the external markers and the internal tumor as well as the repeatability of the respiratory motion. In gated lung stereotactic body radiation therapy (SBRT), the treatment time for each fraction could exceed 30 min due to large fractional dose. Tumor motion may experience pattern changes such as baseline shift during such extended treatment time. The purpose of this study is to analyze tumor motion traces in actual treatment situations and to evaluate the effect of the target baseline shift in gated lung SBRT treatment. Real-time motion data for both the external markers and tumors from 51 lung SBRT treatments with Cyberknife Synchrony technology were analyzed in this study. The treatment time is typically greater than 30 min. The baseline shift was calculated with a rolling average window equivalent to ∼20 s and subtracted from that at the beginning. The magnitude of the baseline shift and its relationship with treatment time were investigated. Phase gating simulation was retrospectively performed on 12 carefully selected treatments with respiratory amplitude larger than 5 mm and regular phases. A customized gating window was defined for each individual treatment. It was found that the baseline shifts are specific to each patient and each fraction. Statistical analysis revealed that more than 69% treatments exhibited increased baseline shifts with the lapse of treatment time. The magnitude of the baseline shift could reach 5.3 mm during a 30 min treatment. Gating simulation showed that tumor excursion was caused mainly by the uncertainties in phase gating simulation and baseline shift, the latter being the primary factor. With a 5 mm gating window, 2 out of 12 treatments in the study group showed significant tumor excursion. Baseline shifts

  13. Study and analysis of how to optimize marketing & sales of a b-to-b company for the target group

    OpenAIRE

    Kauppila, Kasper

    2014-01-01

    Study and analysis of how to optimize the marketing & sales strategy of a b-to-b company for the target group. Case study for Green Fortune Plantwall Oy. This thesis is a case study of Green Fortune Plantwall Oy. The objective of this thesis is to study and analyze how to optimize the current marketing and sales strategy of a small b-to-b company for its target group (i.e. architects and interior designers).

  14. Adolescent survivors: a secondary analysis of a clinical trial targeting behavior change.

    Science.gov (United States)

    Cox, Cheryl L; McLaughlin, Rosemary A; Rai, Shesh N; Steen, Brenda D; Hudson, Melissa M

    2005-08-01

    The late effects of radiation and chemotherapy increase childhood cancer survivors' risk of chronic health problems. Survivors' behavior is important in modifying this risk, yet adolescent and young adult survivors fail to engage in important health-promoting behaviors and frequently practice high-risk behaviors. This secondary analysis re-evaluated a multi-component behavior-change intervention that had previously demonstrated no impact in adolescent survivors of childhood cancer. The parent trial compared 132 adolescent survivors in the intervention arm with 135 in the standard-care arm at baseline and at 1 year for disease and treatment knowledge, perception of late effects risk, and the frequency of health-risk and health-protective behaviors (combined as a single summative measure). In contrast, the secondary analysis examined each of the 14 behaviors separately. Additionally, an analysis of covariance (ANCOVA) was conducted to examine the change in health behaviors while statistically controlling for age, gender, and the wide variation in baseline behaviors. Knowledge (P = 0.038), breast self-examination (BSE) (P junk food consumption decreased (P = 0.052) and smoking abstinence was maintained (P = 0.088). Significant interactions between gender and treatment group were demonstrated. Health-risk and health-protective behaviors cannot be effectively combined in a one-dimensional measure. Gender and age influence the impact of interventions targeting health behavior in survivors. Future trials should include observation of the patient-clinician encounter, more complex sampling methods, and pre-trial knowledge of the distribution of the study behaviors.

  15. Chemical Genetic Analysis and Functional Characterization of Staphylococcal Wall Teichoic Acid 2-Epimerases Reveals Unconventional Antibiotic Drug Targets

    Energy Technology Data Exchange (ETDEWEB)

    Mann, Paul A.; Müller, Anna; Wolff, Kerstin A.; Fischmann, Thierry; Wang, Hao; Reed, Patricia; Hou, Yan; Li, Wenjin; Müller, Christa E.; Xiao, Jianying; Murgolo, Nicholas; Sher, Xinwei; Mayhood, Todd; Sheth, Payal R.; Mirza, Asra; Labroli, Marc; Xiao, Li; McCoy, Mark; Gill, Charles J.; Pinho, Mariana G.; Schneider, Tanja; Roemer, Terry (Merck); (Bonn); (FCT/UNL)

    2016-05-04

    Here we describe a chemical biology strategy performed in Staphylococcus aureus and Staphylococcus epidermidis to identify MnaA, a 2-epimerase that we demonstrate interconverts UDP-GlcNAc and UDP-ManNAc to modulate substrate levels of TarO and TarA wall teichoic acid (WTA) biosynthesis enzymes. Genetic inactivation of mnaA results in complete loss of WTA and dramatic in vitro β-lactam hypersensitivity in methicillin-resistant S. aureus (MRSA) and S. epidermidis (MRSE). Likewise, the β-lactam antibiotic imipenem exhibits restored bactericidal activity against mnaA mutants in vitro and concomitant efficacy against 2-epimerase defective strains in a mouse thigh model of MRSA and MRSE infection. Interestingly, whereas MnaA serves as the sole 2-epimerase required for WTA biosynthesis in S. epidermidis, MnaA and Cap5P provide compensatory WTA functional roles in S. aureus. We also demonstrate that MnaA and other enzymes of WTA biosynthesis are required for biofilm formation in MRSA and MRSE. We further determine the 1.9Å crystal structure of S. aureus MnaA and identify critical residues for enzymatic dimerization, stability, and substrate binding. Finally, the natural product antibiotic tunicamycin is shown to physically bind MnaA and Cap5P and inhibit 2-epimerase activity, demonstrating that it inhibits a previously unanticipated step in WTA biosynthesis. In summary, MnaA serves as a new Staphylococcal antibiotic target with cognate inhibitors predicted to possess dual therapeutic benefit: as combination agents to restore β-lactam efficacy against MRSA and MRSE and as non-bioactive prophylactic agents to prevent Staphylococcal biofilm formation.

  16. Dependency of human target detection performance on clutter and quality of supporting image analysis algorithms in a video surveillance task

    Science.gov (United States)

    Huber, Samuel; Dunau, Patrick; Wellig, Peter; Stein, Karin

    2017-10-01

    Background: In target detection, the success rates depend strongly on human observer performances. Two prior studies tested the contributions of target detection algorithms and prior training sessions. The aim of this Swiss-German cooperation study was to evaluate the dependency of human observer performance on the quality of supporting image analysis algorithms. Methods: The participants were presented 15 different video sequences. Their task was to detect all targets in the shortest possible time. Each video sequence showed a heavily cluttered simulated public area from a different viewing angle. In each video sequence, the number of avatars in the area was altered to 100, 150 and 200 subjects. The number of targets appearing was kept at 10%. The number of marked targets varied from 0, 5, 10, 20 up to 40 marked subjects while keeping the positive predictive value of the detection algorithm at 20%. During the task, workload level was assessed by applying an acoustic secondary task. Detection rates and detection times for the targets were analyzed using inferential statistics. Results: The study found Target Detection Time to increase and Target Detection Rates to decrease with increasing numbers of avatars. The same is true for the Secondary Task Reaction Time while there was no effect on Secondary Task Hit Rate. Furthermore, we found a trend for a u-shaped correlation between the numbers of markings and RTST indicating increased workload. Conclusion: The trial results may indicate useful criteria for the design of training and support of observers in observational tasks.

  17. Decreased prothrombin conversion and reduced thrombin inactivation explain rebalanced thrombin generation in liver cirrhosis.

    Directory of Open Access Journals (Sweden)

    Romy M W Kremers

    Full Text Available Impaired coagulation factor synthesis in cirrhosis causes a reduction of most pro- and anticoagulant factors. Cirrhosis patients show no clear bleeding or thrombotic phenotype, although they are at risk for both types of hemostatic event. Thrombin generation (TG is a global coagulation test and its outcome depends on underlying pro- and anticoagulant processes (prothrombin conversion and thrombin inactivation. We quantified the prothrombin conversion and thrombin inactivation during TG in 30 healthy subjects and 52 Child-Pugh (CP- A, 15 CP-B and 6 CP-C cirrhosis patients to test the hypothesis that coagulation is rebalanced in liver cirrhosis patients. Both prothrombin conversion and thrombin inactivation are reduced in cirrhosis patients. The effect on pro- and anticoagulant processes partially cancel each other out and as a result TG is comparable at 5 pM tissue factor between healthy subjects and patients. This supports the hypothesis of rebalanced hemostasis, as TG in cirrhosis patients remains within the normal range, despite large changes in prothrombin conversion and thrombin inactivation. Nevertheless, in silico analysis shows that normalization of either prothrombin conversion or thrombin inactivation to physiological levels, by for example the administration of prothrombin complex concentrates would cause an elevation of TG, whereas the normalization of both simultaneously maintains a balanced TG. Therefore, cirrhosis patients might require adapted hemostatic treatment.

  18. Mitochondrial isocitrate dehydrogenase is inactivated upon oxidation and reactivated by thioredoxin-dependent reduction in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Keisuke eYoshida

    2014-09-01

    Full Text Available Regulation of mitochondrial metabolism is essential for ensuring cellular growth and maintenance in plants. Based on redox-proteomics analysis, several proteins involved in diverse mitochondrial reactions have been identified as potential redox-regulated proteins. NAD+-dependent isocitrate dehydrogenase (IDH, a key enzyme in the tricarboxylic acid cycle, is one such candidate. In this study, we investigated the redox regulation mechanisms of IDH by biochemical procedures. In contrast to mammalian and yeast counterparts reported to date, recombinant IDH in Arabidopsis mitochondria did not show adenylate-dependent changes in enzymatic activity. Instead, IDH was inactivated by oxidation treatment and partially reactivated by subsequent reduction. Functional IDH forms a heterodimer comprising regulatory (IDH-r and catalytic (IDH-c subunits. IDH-r was determined to be the target of oxidative modifications forming an oligomer via intermolecular disulfide bonds. Mass spectrometric analysis combined with tryptic digestion of IDH-r indicated that Cys128 and Cys216 are involved in intermolecular disulfide bond formation. Furthermore, we showed that mitochondria-localized o-type thioredoxin (Trx-o promotes the reduction of oxidized IDH-r. These results suggest that IDH-r is susceptible to oxidative stress, and Trx-o serves to convert oxidized IDH-r to the reduced form that is necessary for active IDH complex.

  19. Numerical analysis of the feasibility of a beam window for TEF target

    International Nuclear Information System (INIS)

    Obayashi, H.; Takei, H.; Iwamoto, H.; Sasa, T.

    2015-01-01

    In the various research activities for ADS (accelerator-driven systems), the construction of the Transmutation Experimental Facility (TEF) is planned within the framework of the J-PARC project as a preceding step before the construction of a pilot ADS. The ADS proposed by JAEA is a tank-type subcritical reactor with a thermal power of 800 MWth which uses lead-bismuth eutectic (LBE) alloy as a target material and a coolant, driven by a 30 MW superconducting proton linac. The beam window of ADS, which separates the proton accelerator and the LBE subcritical core vessel, is exposed to the high-temperature environment induced by the incidence of proton beam. Therefore, the feasibility of the beam window is the most important factor for the realisation of TEF. The objective of this study is to evaluate the feasibility of a designed beam window of TEF target by the numerical analysis with a three-dimensional model. The analysis was performed by considering: (1) the current density and shape of the incident beam, (2) the thermal-fluid behaviour of LBE around the beam window as a function of the flow rate and inlet temperature, (3) the material and the thickness of the beam window, (4) the structural strength of the beam window. In the reference case, the current density and the profile of the proton beam were 20 μA/cm 2 and a Gaussian shape, respectively. The flow rate of LBE and temperature at the inlet were 1 l/s and 350 C. degrees. The material of a beam window was SUS316 stainless steel 2 mm thick. In this reference case, the maximum velocity of LBE and the maximum temperature located at the top of the beam window were about 1.2 m/sec and 477 C. degrees. By increasing the flow rate of LBE up to 4 l/s, the maximum temperature of a beam window was reduced to around 420 C. degrees. The maximum shear stress was 194 MPa, which was observed at the centre on the outside surface of the beam window. The analysed stress in the reference case was lower than the tolerance level

  20. Road safety risk evaluation and target setting using data envelopment analysis and its extensions.

    Science.gov (United States)

    Shen, Yongjun; Hermans, Elke; Brijs, Tom; Wets, Geert; Vanhoof, Koen

    2012-09-01

    Currently, comparison between countries in terms of their road safety performance is widely conducted in order to better understand one's own safety situation and to learn from those best-performing countries by indicating practical targets and formulating action programmes. In this respect, crash data such as the number of road fatalities and casualties are mostly investigated. However, the absolute numbers are not directly comparable between countries. Therefore, the concept of risk, which is defined as the ratio of road safety outcomes and some measure of exposure (e.g., the population size, the number of registered vehicles, or distance travelled), is often used in the context of benchmarking. Nevertheless, these risk indicators are not consistent in most cases. In other words, countries may have different evaluation results or ranking positions using different exposure information. In this study, data envelopment analysis (DEA) as a performance measurement technique is investigated to provide an overall perspective on a country's road safety situation, and further assess whether the road safety outcomes registered in a country correspond to the numbers that can be expected based on the level of exposure. In doing so, three model extensions are considered, which are the DEA based road safety model (DEA-RS), the cross-efficiency method, and the categorical DEA model. Using the measures of exposure to risk as the model's input and the number of road fatalities as output, an overall road safety efficiency score is computed for the 27 European Union (EU) countries based on the DEA-RS model, and the ranking of countries in accordance with their cross-efficiency scores is evaluated. Furthermore, after applying clustering analysis to group countries with inherent similarity in their practices, the categorical DEA-RS model is adopted to identify best-performing and underperforming countries in each cluster, as well as the reference sets or benchmarks for those

  1. Inactivation of catalase monolayers by irradiation with 100 keV electrons

    International Nuclear Information System (INIS)

    Hahn, M.; Seredynski, J.; Baumeister, W.

    1976-01-01

    A catalase monolayer adsorbed on a layer of arachidic acid deposited on a solid support was irradiated with 100 keV electrons simulating the conditions of electron microscopic imaging. Effective doses were calculated taking into account the angular and energy distribution of backscattered electrons. Enzymatic inactivation was chosen as the criterion for damage and was monitored by a rapid and quantifiable but nevertheless sensitive assay. Dose-response curves revealed that inactivation is a one-hit--multiple-target phenomenon, which is consistent with biochemical evidence for a cooperative function of subunits. The experimentally determined target size coincides fairly well with both calculated cross sections for inelastic interactions based on the atomic composition of catalase and with calculated cross sections for ionizing events based on the chemical bonds involved. This legitimates both types of calculations even for complex biomolecules

  2. Whole genome analysis of CRISPR Cas9 sgRNA off-target homologies via an efficient computational algorithm.

    Science.gov (United States)

    Zhou, Hong; Zhou, Michael; Li, Daisy; Manthey, Joseph; Lioutikova, Ekaterina; Wang, Hong; Zeng, Xiao

    2017-11-17

    The beauty and power of the genome editing mechanism, CRISPR Cas9 endonuclease system, lies in the fact that it is RNA-programmable such that Cas9 can be guided to any genomic loci complementary to a 20-nt RNA, single guide RNA (sgRNA), to cleave double stranded DNA, allowing the introduction of wanted mutations. Unfortunately, it has been reported repeatedly that the sgRNA can also guide Cas9 to off-target sites where the DNA sequence is homologous to sgRNA. Using human genome and Streptococcus pyogenes Cas9 (SpCas9) as an example, this article mathematically analyzed the probabilities of off-target homologies of sgRNAs and discovered that for large genome size such as human genome, potential off-target homologies are inevitable for sgRNA selection. A highly efficient computationl algorithm was developed for whole genome sgRNA design and off-target homology searches. By means of a dynamically constructed sequence-indexed database and a simplified sequence alignment method, this algorithm achieves very high efficiency while guaranteeing the identification of all existing potential off-target homologies. Via this algorithm, 1,876,775 sgRNAs were designed for the 19,153 human mRNA genes and only two sgRNAs were found to be free of off-target homology. By means of the novel and efficient sgRNA homology search algorithm introduced in this article, genome wide sgRNA design and off-target analysis were conducted and the results confirmed the mathematical analysis that for a sgRNA sequence, it is almost impossible to escape potential off-target homologies. Future innovations on the CRISPR Cas9 gene editing technology need to focus on how to eliminate the Cas9 off-target activity.

  3. Some factors affecting urokinase inactivation. [Gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Iwata, Hiroo; Iketa, Yoshito

    1985-10-01

    The enzymatic activity of urokinase adsorbed on various polymer surfaces was measured to study the interaction between protein and polymers. The polymer films on which urokinase was adsorbed were exposed to either a high temperature or ..gamma..-radiation. The thermal inactivation rates were higher on hydrophobic polymers such as poly(ethylene terephthalate), nylon 6, and poly(vinylidene fluoride) than hydrophilic polymers like cellulose and ethylene-vinyl alcohol copolymer, indicating their substantial dependence on the interfacial free energy between the polymer and water. A similar dependence was also seen for the ..gamma..-radiation inactivation. Urokinase adsorbed on the hydrophobic polymers lost more easily its enzymatic activity by exposure to ..gamma..-radiation. The interfacial free energy seems to be one of the driving forces to denaturate proteins on polymers.

  4. Inactivation of biological substances by local heating

    Energy Technology Data Exchange (ETDEWEB)

    Saito, Masahiro [Kyoto Univ., Kumatori, Osaka (Japan). Research Reactor Inst.

    1982-09-01

    Mechanism of inactivation of biological substances caused by local heating was investigated. The effect of hot-zone formation by local heating on reaction of radicals was previously evaluated. The thermal increase in a hot zone due to low energy LET x-rays had little effect on reactibility of the radicals, but, in a hot zone caused by high energy LET x-rays, formed radicals seemed immediately react to active biological molecules to inactivate them. Direct thermal effect on biological molecules was analysed. Thermal increase in a hot zone may induce degenaration of biological molecules which seems to occur in a short time judged from the extension of a hot zone and the duration of high temperature.

  5. Immunogenicity of UV-inactivated measles virus

    International Nuclear Information System (INIS)

    Zahorska, R.; Mazur, N.; Korbecki, M.

    1978-01-01

    By means of the antigen extinction limit test it was shown that a triple dose vaccination of guinea pigs with UV-inactivated measles virus gave better results, than a single dose vaccination which was proved by the very low immunogenicity index. For both vaccination schemes (single and triple) the immune response was only sligthly influenced by a change of dose from 10 5 to 10 6 HadU 50 /ml or by the addition of aluminum adjuvant. In the antigen extinction limit test the antibody levels were determined by two methods (HIT and NT) the results of which were statistically equivalent. The UV-inactivated measles virus was also found to induce hemolysis-inhibiting antibodies. (orig.) [de

  6. Geospatial analysis of emergency department visits for targeting community-based responses to the opioid epidemic.

    Directory of Open Access Journals (Sweden)

    Daniel A Dworkis

    Full Text Available The opioid epidemic in the United States carries significant morbidity and mortality and requires a coordinated response among emergency providers, outpatient providers, public health departments, and communities. Anecdotally, providers across the spectrum of care at Massachusetts General Hospital (MGH in Boston, MA have noticed that Charlestown, a community in northeast Boston, has been particularly impacted by the opioid epidemic and needs both emergency and longer-term resources. We hypothesized that geospatial analysis of the home addresses of patients presenting to the MGH emergency department (ED with opioid-related emergencies might identify "hot spots" of opioid-related healthcare needs within Charlestown that could then be targeted for further investigation and resource deployment. Here, we present a geospatial analysis at the United States census tract level of the home addresses of all patients who presented to the MGH ED for opioid-related emergency visits between 7/1/2012 and 6/30/2015, including 191 visits from 100 addresses in Charlestown, MA. Among the six census tracts that comprise Charlestown, we find a 9.5-fold difference in opioid-related ED visits, with 45% of all opioid-related visits from Charlestown originating in tract 040401. The signal from this census tract remains strong after adjusting for population differences between census tracts, and while this tract is one of the higher utilizing census tracts in Charlestown of the MGH ED for all cause visits, it also has a 2.9-fold higher rate of opioid-related visits than the remainder of Charlestown. Identifying this hot spot of opioid-related emergency needs within Charlestown may help re-distribute existing resources efficiently, empower community and ED-based physicians to advocate for their patients, and serve as a catalyst for partnerships between MGH and local community groups. More broadly, this analysis demonstrates that EDs can use geospatial analysis to address

  7. Stakeholder engagement analysis - a bioethics dilemma in patient-targeted intervention: patients with temporomandibular joint disorders.

    Science.gov (United States)

    Barkhordarian, Andre; Demerjian, Gary; Jan, Allison; Sama, Nateli; Nguyen, Mia; Du, Angela; Chiappelli, Francesco

    2015-01-20

    Modern health care in the field of Medicine, Dentistry and Nursing is grounded in fundamental philosophy and epistemology of translational science. Recently in the U.S major national initiatives have been implemented in the hope of closing the gaps that sometimes exist between the two fundamental components of translational science, the translational research and translational effectiveness. Subsequent to these initiatives, many improvements have been made; however, important bioethical issues and limitations do still exist that need to be addressed. One such issue is the stakeholder engagement and its assessment and validation. Federal, state and local organizations such as PCORI and AHRQ concur that the key to a better understanding of the relationship between translational research and translational effectiveness is the assessment of the extent to which stakeholders are actively engaged in the translational process of healthcare. The stakeholder engagement analysis identifies who the stakeholders are, maps their contribution and involvement, evaluates their priorities and opinions, and accesses their current knowledge base. This analysis however requires conceptualization and validation from the bioethics standpoint. Here, we examine the bioethical dilemma of stakeholder engagement analysis in the context of the person-environment fit (PE-fit) theoretical model. This model is an approach to quantifying stakeholder engagement analysis for the design of patient-targeted interventions. In our previous studies of Alzheimer patients, we have developed, validated and used a simple instrument based on the PE-fit model that can be adapted and utilized in a much less studied pathology as a clinical model that has a wide range of symptoms and manifestations, the temporomandibular joint disorders (TMD). The temporomandibular joint (TMJ) is the jaw joint endowed with sensory and motor innervations that project from within the central nervous system and its dysfunction can

  8. Neonicotinoid insecticides negatively affect performance measures of non‐target terrestrial arthropods: a meta‐analysis

    Science.gov (United States)

    Main, Anson; Webb, Elisabeth B.; Goyne, Keith W.; Mengel, Doreen C.

    2018-01-01

    Neonicotinoid insecticides are currently the fastest‐growing and most widely used insecticide class worldwide. Valued for their versatility in application, these insecticides may cause deleterious effects in a range of non‐target (beneficial) arthropods. However, it remains unclear whether strong patterns exist in terms of their major effects, if broad measures of arthropod performance are negatively affected, or whether different functional groups are equally vulnerable. Here, we present a meta‐analysis of 372 observations from 44 field and laboratory studies that describe neonicotinoid effects on 14 arthropod orders across five broad performance measures: abundance, behavior, condition, reproductive success, and survival. Across studies, neonicotinoids negatively affected all performance metrics evaluated; however, magnitude of the effects varied. Arthropod behavior and survival were the most negatively affected and abundance was the least negatively affected. Effects on arthropod functional groups were inconsistent. Pollinator condition, reproductive success, and survival were significantly lower in neonicotinoid treatments compared to untreated controls; whereas, neonicotinoid effects on detritivores were not significant. Although magnitude of arthropod response to neonicotinoids varied among performance measures and functional groups, we documented a consistent negative relationship between exposure to neonicotinoid insecticides in published studies and beneficial arthropod performance.

  9. Shilling Attacks Detection in Recommender Systems Based on Target Item Analysis.

    Science.gov (United States)

    Zhou, Wei; Wen, Junhao; Koh, Yun Sing; Xiong, Qingyu; Gao, Min; Dobbie, Gillian; Alam, Shafiq

    2015-01-01

    Recommender systems are highly vulnerable to shilling attacks, both by individuals and groups. Attackers who introduce biased ratings in order to affect recommendations, have been shown to negatively affect collaborative filtering (CF) algorithms. Previous research focuses only on the differences between genuine profiles and attack profiles, ignoring the group characteristics in attack profiles. In this paper, we study the use of statistical metrics to detect rating patterns of attackers and group characteristics in attack profiles. Another question is that most existing detecting methods are model specific. Two metrics, Rating Deviation from Mean Agreement (RDMA) and Degree of Similarity with Top Neighbors (DegSim), are used for analyzing rating patterns between malicious profiles and genuine profiles in attack models. Building upon this, we also propose and evaluate a detection structure called RD-TIA for detecting shilling attacks in recommender systems using a statistical approach. In order to detect more complicated attack models, we propose a novel metric called DegSim' based on DegSim. The experimental results show that our detection model based on target item analysis is an effective approach for detecting shilling attacks.

  10. High-velocity Penetration of Concrete Targets with Three Types of Projectiles: Experiments and Analysis

    Directory of Open Access Journals (Sweden)

    Shuang Zhang

    Full Text Available Abstract This study conducted high-velocity penetration experiments using conventional ogive-nose, double-ogive-nose, and grooved-tapered projectiles of approximately 2.5 kg and initial velocities between 1000 and 1360 m/s to penetrate or perforate concrete targets with unconfined compressive strengths of nominally 40MPa. The penetration performance data of these three types of projectiles with two different types of materials (i.e., AerMet100 and DT300 were obtained. The crater depth model considering both the projectile mass and the initial velocity was proposed based on the test results and a theoretical analysis. The penetration ability and the trajectory stability of these three projectile types were compared and analyzed accordingly. The results showed that, under these experimental conditions, the effects of these two different kinds of projectile materials on the penetration depth and mass erosion rate of projectile were not obvious. The existing models could not reflect the crater depths for projectiles of greater weights or higher velocities, whereas the new model established in this study was reliable. The double-ogive-nose has a certain effect of drag reduction. Thus, the double-ogive-nose projectile has a higher penetration ability than the conventional ogive-nose projectile. Meanwhile, the grooved-tapered projectile has a better trajectory stability, because the convex parts of tapered shank generated the restoring moment to stabilize the trajectory.

  11. Gas analysis within remote porous targets using LIDAR multi-scatter techniques

    Science.gov (United States)

    Guan, Z. G.; Lewander, M.; Grönlund, R.; Lundberg, H.; Svanberg, S.

    2008-11-01

    Light detection and ranging (LIDAR) experiments are normally pursued for range resolved atmospheric gas measurements or for analysis of solid target surfaces using fluorescence of laser-induced breakdown spectroscopy. In contrast, we now demonstrate the monitoring of free gas enclosed in pores of materials, subject to impinging laser radiation, employing the photons emerging back to the surface laterally of the injection point after penetrating the medium in heavy multiple scattering processes. The directly reflected light is blocked by a beam stop. The technique presented is a remote version of the newly introduced gas in scattering media absorption spectroscopy (GASMAS) technique, which so far was pursued with the injection optics and the detector in close contact with the sample. Feasibility measurements of LIDAR-GASMAS on oxygen in polystyrene foam were performed at a distance of 6 m. Multiple-scattering induced delays of the order of 50 ns, which corresponds to 15 m optical path length, were observed. First extensions to a range of 60 m are discussed. Remote observation of gas composition anomalies in snow using differential absorption LIDAR (DIAL) may find application in avalanche victim localization or for leak detection in snow-covered natural gas pipelines. Further, the techniques may be even more useful for short-range, non-intrusive GASMAS measurements, e.g., on packed food products.

  12. Shilling Attacks Detection in Recommender Systems Based on Target Item Analysis

    Science.gov (United States)

    Zhou, Wei; Wen, Junhao; Koh, Yun Sing; Xiong, Qingyu; Gao, Min; Dobbie, Gillian; Alam, Shafiq

    2015-01-01

    Recommender systems are highly vulnerable to shilling attacks, both by individuals and groups. Attackers who introduce biased ratings in order to affect recommendations, have been shown to negatively affect collaborative filtering (CF) algorithms. Previous research focuses only on the differences between genuine profiles and attack profiles, ignoring the group characteristics in attack profiles. In this paper, we study the use of statistical metrics to detect rating patterns of attackers and group characteristics in attack profiles. Another question is that most existing detecting methods are model specific. Two metrics, Rating Deviation from Mean Agreement (RDMA) and Degree of Similarity with Top Neighbors (DegSim), are used for analyzing rating patterns between malicious profiles and genuine profiles in attack models. Building upon this, we also propose and evaluate a detection structure called RD-TIA for detecting shilling attacks in recommender systems using a statistical approach. In order to detect more complicated attack models, we propose a novel metric called DegSim’ based on DegSim. The experimental results show that our detection model based on target item analysis is an effective approach for detecting shilling attacks. PMID:26222882

  13. Targeted liquid chromatography–mass spectrometry analysis of serum acylcarnitines in acetaminophen toxicity in children

    Science.gov (United States)

    Bhattacharyya, Sudeepa; Yan, Ke; Pence, Lisa; Simpson, Pippa M; Gill, Pritmohinder; Letzig, Lynda G; Beger, Richard D; Sullivan, Janice E; Kearns, Gregory L; Reed, Michael D; Marshall, James D; Van Den Anker, John N; James, Laura P

    2014-01-01

    Aim Long-chain acylcarnitines have been postulated to be sensitive biomarkers of acetaminophen (APAP)-induced hepatotoxicity in mouse models. In the following study, the relationship of acylcarnitines with other known indicators of APAP toxicity was examined in children receiving low-dose (therapeutic) and high-dose (‘overdose’ or toxic ingestion) exposure to APAP. Materials & methods The study included three subject groups: group A (therapeutic dose, n = 187); group B (healthy controls, n = 23); and group C (overdose, n = 62). Demographic, clinical and laboratory data were collected for each subject. Serum samples were used for measurement of APAP protein adducts, a biomarker of the oxidative metabolism of APAP and for targeted metabolomics analysis of serum acylcarnitines using ultra performance liquid chromatography–triple-quadrupole mass spectrometry. Results Significant increases in oleoyl- and palmitoyl-carnitines were observed with APAP exposure (low dose and overdose) compared with controls. Significant increases in serum ALT, APAP protein adducts and acylcarnitines were observed in overdose children that received delayed treatment (time to treatment from overdose >24 h) with the antidote N-acetylcysteine. Time to peak APAP protein adducts in serum was shorter than that of the acylcarnitines and serum ALT. Conclusion Perturbations in long-chain acylcarnitines in children with APAP toxicity suggest that mitochrondrial injury and associated impairment in the β-oxidation of fatty acids are clinically relevant as biomarkers of APAP toxicity. PMID:24521011

  14. TARGETED PRINCIPLE COMPONENT ANALYSIS: A NEW MOTION ARTIFACT CORRECTION APPROACH FOR NEAR-INFRARED SPECTROSCOPY.

    Science.gov (United States)

    Yücel, Meryem A; Selb, Juliette; Cooper, Robert J; Boas, David A

    2014-03-01

    As near-infrared spectroscopy (NIRS) broadens its application area to different age and disease groups, motion artifacts in the NIRS signal due to subject movement is becoming an important challenge. Motion artifacts generally produce signal fluctuations that are larger than physiological NIRS signals, thus it is crucial to correct for them before obtaining an estimate of stimulus evoked hemodynamic responses. There are various methods for correction such as principle component analysis (PCA), wavelet-based filtering and spline interpolation. Here, we introduce a new approach to motion artifact correction, targeted principle component analysis (tPCA), which incorporates a PCA filter only on the segments of data identified as motion artifacts. It is expected that this will overcome the issues of filtering desired signals that plagues standard PCA filtering of entire data sets. We compared the new approach with the most effective motion artifact correction algorithms on a set of data acquired simultaneously with a collodion-fixed probe (low motion artifact content) and a standard Velcro probe (high motion artifact content). Our results show that tPCA gives statistically better results in recovering hemodynamic response function (HRF) as compared to wavelet-based filtering and spline interpolation for the Velcro probe. It results in a significant reduction in mean-squared error (MSE) and significant enhancement in Pearson's correlation coefficient to the true HRF. The collodion-fixed fiber probe with no motion correction performed better than the Velcro probe corrected for motion artifacts in terms of MSE and Pearson's correlation coefficient. Thus, if the experimental study permits, the use of a collodion-fixed fiber probe may be desirable. If the use of a collodion-fixed probe is not feasible, then we suggest the use of tPCA in the processing of motion artifact contaminated data.

  15. TARGETED PRINCIPLE COMPONENT ANALYSIS: A NEW MOTION ARTIFACT CORRECTION APPROACH FOR NEAR-INFRARED SPECTROSCOPY

    Science.gov (United States)

    YÜCEL, MERYEM A.; SELB, JULIETTE; COOPER, ROBERT J.; BOAS, DAVID A.

    2014-01-01

    As near-infrared spectroscopy (NIRS) broadens its application area to different age and disease groups, motion artifacts in the NIRS signal due to subject movement is becoming an important challenge. Motion artifacts generally produce signal fluctuations that are larger than physiological NIRS signals, thus it is crucial to correct for them before obtaining an estimate of stimulus evoked hemodynamic responses. There are various methods for correction such as principle component analysis (PCA), wavelet-based filtering and spline interpolation. Here, we introduce a new approach to motion artifact correction, targeted principle component analysis (tPCA), which incorporates a PCA filter only on the segments of data identified as motion artifacts. It is expected that this will overcome the issues of filtering desired signals that plagues standard PCA filtering of entire data sets. We compared the new approach with the most effective motion artifact correction algorithms on a set of data acquired simultaneously with a collodion-fixed probe (low motion artifact content) and a standard Velcro probe (high motion artifact content). Our results show that tPCA gives statistically better results in recovering hemodynamic response function (HRF) as compared to wavelet-based filtering and spline interpolation for the Velcro probe. It results in a significant reduction in mean-squared error (MSE) and significant enhancement in Pearson’s correlation coefficient to the true HRF. The collodion-fixed fiber probe with no motion correction performed better than the Velcro probe corrected for motion artifacts in terms of MSE and Pearson’s correlation coefficient. Thus, if the experimental study permits, the use of a collodion-fixed fiber probe may be desirable. If the use of a collodion-fixed probe is not feasible, then we suggest the use of tPCA in the processing of motion artifact contaminated data. PMID:25360181

  16. 3D numerical thermal stress analysis of the high power target for the SLC Positron Source

    International Nuclear Information System (INIS)

    Reuter, E.M.; Hodgson, J.A.

    1991-05-01

    The volumetrically nonuniform power deposition of the incident 33 GeV electron beam in the SLC Positron Source Target is hypothesized to be the most likely cause target failure. The resultant pulsed temperature distributions are known to generate complicated stress fields with no known closed-form analytical solution. 3D finite element analyses of these temperature distributions and associated thermal stress fields in the new High Power Target are described here. Operational guidelines based on the results of these analyses combined with assumptions made about the fatigue characteristics of the exotic target material are proposed. 6 refs., 4 figs

  17. Identification of putative drug targets in Vancomycin-resistant Staphylococcus aureus (VRSA) using computer aided protein data analysis.

    Science.gov (United States)

    Hasan, Md Anayet; Khan, Md Arif; Sharmin, Tahmina; Hasan Mazumder, Md Habibul; Chowdhury, Afrin Sultana

    2016-01-01

    Vancomycin-resistant Staphylococcus aureus (VRSA) is a Gram-positive, facultative aerobic bacterium which is evolved from the extensive exposure of Vancomycin to Methicillin resistant S. aureus (MRSA) that had become the most common cause of hospital and community-acquired infections. Due to the emergence of different antibiotic resistance strains, there is an exigency to develop novel drug targets to address the provocation of multidrug-resistant bacteria. In this study, in-silico genome subtraction methodology was used to design potential and pathogen specific drug targets against VRSA. Our study divulged 1987 proteins from the proteome of 34,549 proteins, which have no homologues in human genome after sequential analysis through CD-HIT and BLASTp. The high stringency analysis of the remaining proteins against database of essential genes (DEG) resulted in 169 proteins which are essential for S. aureus. Metabolic pathway analysis of human host and pathogen by KAAS at the KEGG server sorted out 19 proteins involved in unique metabolic pathways. 26 human non-homologous membrane-bound essential proteins including 4 which were also involved in unique metabolic pathway were deduced through PSORTb, CELLO v.2.5, ngLOC. Functional classification of uncharacterized proteins through SVMprot derived 7 human non-homologous membrane-bound hypothetical essential proteins. Study of potential drug target against Drug Bank revealed pbpA-penicillin-binding protein 1 and hypothetical protein MQW_01796 as the best drug target candidate. 2D structure was predicted by PRED-TMBB, 3D structure and functional analysis was also performed. Protein-protein interaction network of potential drug target proteins was analyzed by using STRING. The identified drug targets are expected to have great potential for designing novel drugs against VRSA infections and further screening of the compounds against these new targets may result in the discovery of novel therapeutic compounds that can be

  18. Female meiotic sex chromosome inactivation in chicken.

    Directory of Open Access Journals (Sweden)

    Sam Schoenmakers

    2009-05-01

    Full Text Available During meiotic prophase in male mammals, the heterologous X and Y chromosomes remain largely unsynapsed, and meiotic sex chromosome inactivation (MSCI leads to formation of the transcriptionally silenced XY body. In birds, the heterogametic sex is female, carrying Z and W chromosomes (ZW, whereas males have the homogametic ZZ constitution. During chicken oogenesis, the heterologous ZW pair reaches a state of complete heterologous synapsis, and this might enable maintenance of transcription of Z- and W chromosomal genes during meiotic prophase. Herein, we show that the ZW pair is transiently silenced, from early pachytene to early diplotene using immunocytochemistry and gene expression analyses. We propose that ZW inactivation is most likely achieved via spreading of heterochromatin from the W on the Z chromosome. Also, persistent meiotic DNA double-strand breaks (DSBs may contribute to silencing of Z. Surprisingly, gammaH2AX, a marker of DSBs, and also the earliest histone modification that is associated with XY body formation in mammalian and marsupial spermatocytes, does not cover the ZW during the synapsed stage. However, when the ZW pair starts to desynapse, a second wave of gammaH2AX accumulates on the unsynapsed regions of Z, which also show a reappearance of the DSB repair protein RAD51. This indicates that repair of meiotic DSBs on the heterologous part of Z is postponed until late pachytene/diplotene, possibly to avoid recombination with regions on the heterologously synapsed W chromosome. Two days after entering diplotene, the Z looses gammaH2AX and shows reactivation. This is the first report of meiotic sex chromosome inactivation in a species with female heterogamety, providing evidence that this mechanism is not specific to spermatogenesis. It also indicates the presence of an evolutionary force that drives meiotic sex chromosome inactivation independent of the final achievement of synapsis.

  19. Inactivation of Anandamide Signaling: A Continuing Debate

    Directory of Open Access Journals (Sweden)

    Wael E. Houssen

    2010-10-01

    Full Text Available Since the first endocannabinoid anandamide was identified in 1992, extensive research has been conducted to characterize the elements of the tightly controlled endocannabinoid signaling system. While it was established that the activity of endocannabinoids are terminated by a two-step process that includes cellular uptake and degradation, there is still a continuing debate about the mechanistic role of these processes in inactivating anandamide signals.

  20. Photodynamic inactivation of antibiotic-resistant pathogens

    International Nuclear Information System (INIS)

    Paronyan, M.H.

    2015-01-01

    Nowadays methicillin-resistant strain Staphylococcus aureus (MRSA) is one of the most widespread multiresistant bacteria. Photodynamic inactivation (PDI) of microorganisms by photosensitizers (PS) may be an effective and alternative therapeutic option against antibiotic resistant bacteria. The effectiveness of new PS cationic porphyrin Zn-TBut4PyP was tested on two strains of S. aureus (MRSA and methicillin-sensitive S. aureus). It is shown that Zn-TBut4PyP has high photodynamic activity against both strains

  1. Epigenetic inactivation of CHFR in human tumors

    OpenAIRE

    Toyota, Minoru; Sasaki, Yasushi; Satoh, Ayumi; Ogi, Kazuhiro; Kikuchi, Takefumi; Suzuki, Hiromu; Mita, Hiroaki; Tanaka, Nobuyuki; Itoh, Fumio; Issa, Jean-Pierre J.; Jair, Kam-Wing; Schuebel, Kornel E.; Imai, Kohzoh; Tokino, Takashi

    2003-01-01

    Cell-cycle checkpoints controlling the orderly progression through mitosis are frequently disrupted in human cancers. One such checkpoint, entry into metaphase, is regulated by the CHFR gene encoding a protein possessing forkhead-associated and RING finger domains as well as ubiquitin–ligase activity. Although defects in this checkpoint have been described, the molecular basis and prevalence of CHFR inactivation in human tumors are still not fully understood. To address this question, w...

  2. Inactivation of human norovirus using chemical sanitizers.

    Science.gov (United States)

    Kingsley, David H; Vincent, Emily M; Meade, Gloria K; Watson, Clytrice L; Fan, Xuetong

    2014-02-03

    The porcine gastric mucin binding magnetic bead (PGM-MB) assay was used to evaluate the ability of chlorine, chlorine dioxide, peroxyacetic acid, hydrogen peroxide, and trisodium phosphate to inactivate human norovirus within 10% stool filtrate. One-minute free chlorine treatments at concentrations of 33 and 189 ppm reduced virus binding in the PGM-MB assay by 1.48 and 4.14 log₁₀, respectively, suggesting that chlorine is an efficient sanitizer for inactivation of human norovirus (HuNoV). Five minute treatments with 5% trisodium phosphate (pH~12) reduced HuNoV binding by 1.6 log₁₀, suggesting that TSP, or some other high pH buffer, could be used to treat food and food contact surfaces to reduce HuNoV. One minute treatments with 350 ppm chlorine dioxide dissolved in water did not reduce PGM-MB binding, suggesting that the sanitizer may not be suitable for HuNoV inactivation in liquid form. However a 60-min treatment with 350 ppm chlorine dioxide did reduce human norovirus by 2.8 log₁₀, indicating that chlorine dioxide had some, albeit limited, activity against HuNoV. Results also suggest that peroxyacetic acid has limited effectiveness against human norovirus, since 1-min treatments with up to 195 ppm reduced human norovirus binding by chlorine (sodium hypochlorite) as a HuNoV disinfectant wherever possible. Copyright © 2013. Published by Elsevier B.V.

  3. Radical inactivation of a biological sulphydryl molecule

    International Nuclear Information System (INIS)

    Lin, W.S.; Lal, M.; Gaucher, G.M.; Armstrong, D.A.

    1977-01-01

    Reactive species produced from the free radical-induced chain oxidation of low molecular weight sulphydryl-containing molecules in aerated solutions deactivate the sulphydryl-containing enzyme papain, forming both reparable mixed disulphides and non-reparable products. This inactivation is highly efficient for penicillamine and glutathione, but almost negligible with cysteine, which is a protector of papain for [cysteine] / [papain] >= 5 under all conditions used. In the case of glutathione, superoxide dismutase caused only a small reduction in the inactivation and peroxide yields were small, implying that the deactivating species are not .O 2 - but RSOO. radicals or products from them. For penicillamine, however, dimutase was highly effective and the peroxide yields were relatively large, demonstrating that .O 2 - or a radical with similar capabilities for forming H 2 O 2 and being deactivated by dismutase was involved. Although in the presence of dismutase penicillamine is a better protector of non-reparable papain inactivation than glutathione, it suffers from a deficiency in that the papain-penicillamine mixed disulphide, which is always formed, cannot be repaired by spontaneous reaction with RSH molecules. (author)

  4. Alcohol harm reduction advertisements: a content analysis of topic, objective, emotional tone, execution and target audience.

    Science.gov (United States)

    Dunstone, Kimberley; Brennan, Emily; Slater, Michael D; Dixon, Helen G; Durkin, Sarah J; Pettigrew, Simone; Wakefield, Melanie A

    2017-04-11

    Public health mass media campaigns may contribute to reducing the health and social burden attributed to alcohol consumption, but little is known about which advertising characteristics have been used, or have been effective, in alcohol harm reduction campaigns to date. As a first step towards encouraging further research to identify the impact of various advertising characteristics, this study aimed to systematically identify and examine the content of alcohol harm reduction advertisements (ads). Ads were identified through an exhaustive internet search of Google, YouTube, Vimeo, and relevant government and health agency websites. Eligible ads were: English language, produced between 2006 and 2014, not primarily focused on drink-driving or alcohol in pregnancy, and not alcohol industry funded. Systematic content analysis of all ads was performed; each ad was double-coded. In total, 110 individual ads from 72 different alcohol harm reduction campaigns were identified, with the main source countries being Australia (40%) and the United Kingdom (26%). The dominant topic for 52% of ads was short-term harms, while 10% addressed long-term harms, 18% addressed underage drinking, 17% communicated a how-to-change message, and 3% advocated for policy change. The behavioural objective of most ads was to motivate audiences to reduce their alcohol consumption (38%) or to behave responsibly and/or not get drunk when drinking (33%). Only 10% of all ads mentioned low-risk drinking guidelines. Eighty-seven percent of ads used a dramatisation execution style and 74% had a negative emotional tone. Ninety percent of ads contained messages or content that appeared to target adults, and 36% specifically targeted young adults. Some message attributes have been employed more frequently than others, suggesting several promising avenues for future audience or population-based research to compare the relative effectiveness of different characteristics of alcohol harm reduction ads. Given

  5. Alcohol harm reduction advertisements: a content analysis of topic, objective, emotional tone, execution and target audience

    Directory of Open Access Journals (Sweden)

    Kimberley Dunstone

    2017-04-01

    Full Text Available Abstract Background Public health mass media campaigns may contribute to reducing the health and social burden attributed to alcohol consumption, but little is known about which advertising characteristics have been used, or have been effective, in alcohol harm reduction campaigns to date. As a first step towards encouraging further research to identify the impact of various advertising characteristics, this study aimed to systematically identify and examine the content of alcohol harm reduction advertisements (ads. Method Ads were identified through an exhaustive internet search of Google, YouTube, Vimeo, and relevant government and health agency websites. Eligible ads were: English language, produced between 2006 and 2014, not primarily focused on drink-driving or alcohol in pregnancy, and not alcohol industry funded. Systematic content analysis of all ads was performed; each ad was double-coded. Results In total, 110 individual ads from 72 different alcohol harm reduction campaigns were identified, with the main source countries being Australia (40% and the United Kingdom (26%. The dominant topic for 52% of ads was short-term harms, while 10% addressed long-term harms, 18% addressed underage drinking, 17% communicated a how-to-change message, and 3% advocated for policy change. The behavioural objective of most ads was to motivate audiences to reduce their alcohol consumption (38% or to behave responsibly and/or not get drunk when drinking (33%. Only 10% of all ads mentioned low-risk drinking guidelines. Eighty-seven percent of ads used a dramatisation execution style and 74% had a negative emotional tone. Ninety percent of ads contained messages or content that appeared to target adults, and 36% specifically targeted young adults. Conclusions Some message attributes have been employed more frequently than others, suggesting several promising avenues for future audience or population-based research to compare the relative effectiveness of

  6. Targeting for energy efficiency and improved energy collaboration between different companies using total site analysis (TSA)

    International Nuclear Information System (INIS)

    Hackl, Roman; Andersson, Eva; Harvey, Simon

    2011-01-01

    Rising fuel prices, increasing costs associated with emissions of green house gases and the threat of global warming make efficient use of energy more and more important. Industrial clusters have the potential to significantly increase energy efficiency by energy collaboration. In this paper Sweden's largest chemical cluster is analysed using the total site analysis (TSA) method. TSA delivers targets for the amount of utility consumed and generated through excess energy recovery by the different processes. The method enables investigation of opportunities to deliver waste heat from one process to another using a common utility system. The cluster consists of 5 chemical companies producing a variety of products, including polyethylene (PE), polyvinyl chloride (PVC), amines, ethylene, oxygen/nitrogen and plasticisers. The companies already work together by exchanging material streams. In this study the potential for energy collaboration is analysed in order to reach an industrial symbiosis. The overall heating and cooling demands of the site are around 442 MW and 953 MW, respectively. 122 MW of heat is produced in boilers and delivered to the processes. TSA is used to stepwise design a site-wide utility system which improves energy efficiency. It is shown that heat recovery in the cluster can be increased by 129 MW, i.e. the current utility demand could be completely eliminated and further 7 MW excess steam can be made available. The proposed retrofitted utility system involves the introduction of a site-wide hot water circuit, increased recovery of low pressure steam and shifting of heating steam pressure to lower levels in a number heat exchangers when possible. Qualitative evaluation of the suggested measures shows that 60 MW of the savings potential could to be achieved with moderate changes to the process utility system corresponding to 50% of the heat produced from purchased fuel in the boilers of the cluster. Further analysis showed that after implementation

  7. Carbodiimide Inactivation of MMPs and Effect on Dentin Bonding

    Science.gov (United States)

    Mazzoni, A.; Apolonio, F.M.; Saboia, V.P.A.; Santi, S.; Angeloni, V.; Checchi, V.; Curci, R.; Di Lenarda, R.; Tay, F.R.; Pashley, D.H.; Breschi, L.

    2014-01-01

    The use of protein cross-linking agents during bonding procedures has been recently proposed to improve bond durability. This study aimed to use zymography and in situ zymography techniques to evaluate the ability of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) cross-linker to inhibit matrix metalloproteinase (MMP) activity. The hypotheses tested were that: (1) bonding procedures increase dentin gelatinolytic activity and (2) EDC pre-treatment prevents this enzymatic activity. The zymographic assay was performed on protein extracts obtained from dentin powder treated with Optibond FL or Scotchbond 1XT with or without 0.3M EDC pre-treatment. For in situ zymography, adhesive/dentin interfaces were created with the same adhesives applied to acid-etched dentin slabs pre-treated or not with EDC conditioner. Zymograms revealed increased expression of dentin endogenous MMP-2 and -9 after adhesive application, while the use of EDC as a primer inactivated dentin gelatinases. Results of in situ zymograpy showed that hybrid layers of tested adhesives exhibited intense collagenolytic activity, while almost no fluorescence signal was detected when specimens were pre-treated with EDC. The correlative analysis used in this study demonstrated that EDC could contribute to inactivate endogenous dentin MMPs within the hybrid layer created by etch-and-rinse adhesives. PMID:24334409

  8. CFD analysis of a liquid mercury target for the National Spallation Neutron Source

    International Nuclear Information System (INIS)

    Wendel, M.W.; Tov, M.S.

    1997-01-01

    Computational fluid dynamics (CFD) is being used to analyze the design of the National Spallation Neutron Source (NSNS) target. The target is subjected to the neutronic (internal) heat generation that results from the proton collisions with the mercury nuclei. The liquid mercury simultaneously serves as the neutronic target medium, transports away the heat generated within itself, and cools the metallic target structure. Recirculation and stagnation zones within the target are of particular concern because of the likelihood that they will result in local hot spots. These zones exist because the most feasible target designs include a complete U-turn flow redirection. Although the primary concern is that the target is adequately cooled, the pressure drop from inlet to outlet must also be considered because pressure drop directly affects structural loading and required pumping power. Various design options have been considered in an effort to satisfy these design criteria. Significant improvements to the design have been recommended based on the results. Detailed results are presented for the current target design including a comparison with published pressure-drop data. Comparisons are also made with forced convection heat transfer data for liquid mercury flow in circular tubes

  9. An Automatic Multi-Target Independent Analysis Framework for Non-Planar Infrared-Visible Registration.

    Science.gov (United States)

    Sun, Xinglong; Xu, Tingfa; Zhang, Jizhou; Zhao, Zishu; Li, Yuankun

    2017-07-26

    In this paper, we propose a novel automatic multi-target registration framework for non-planar infrared-visible videos. Previous approaches usually analyzed multiple targets together and then estimated a global homography for the whole scene, however, these cannot achieve precise multi-target registration when the scenes are non-planar. Our framework is devoted to solving the problem using feature matching and multi-target tracking. The key idea is to analyze and register each target independently. We present a fast and robust feature matching strategy, where only the features on the corresponding foreground pairs are matched. Besides, new reservoirs based on the Gaussian criterion are created for all targets, and a multi-target tracking method is adopted to determine the relationships between the reservoirs and foreground blobs. With the matches in the corresponding reservoir, the homography of each target is computed according to its moving state. We tested our framework on both public near-planar and non-planar datasets. The results demonstrate that the proposed framework outperforms the state-of-the-art global registration method and the manual global registration matrix in all tested datasets.

  10. A Bayesian analysis of the mixed labelling phenomenon in two-target tracking

    NARCIS (Netherlands)

    Aoki, E.H.; Boers, Y.; Svensson, L.; Mandal, Pranab K.; Bagchi, Arunabha

    In mulit-target tracking and labelling (MTTL), mixed labelling corresponds to a situation where there is ambiguity in labelling, i.e. in the assignment of labels to locations (where a "location" here means simply an unlabelled single-target state. The phenomenon is well-known in literature, and

  11. Effects of pulvinar inactivation on spatial decision-making between equal and asymmetric reward options.

    Science.gov (United States)

    Wilke, Melanie; Kagan, Igor; Andersen, Richard A

    2013-08-01

    The ability to selectively process visual inputs and to decide between multiple movement options in an adaptive manner is critical for survival. Such decisions are known to be influenced by factors such as reward expectation and visual saliency. The dorsal pulvinar connects to a multitude of cortical areas that are involved in visuospatial memory and integrate information about upcoming eye movements with expected reward values. However, it is unclear whether the dorsal pulvinar is critically involved in spatial memory and reward-based oculomotor decision behavior. To examine this, we reversibly inactivated the dorsal portion of the pulvinar while monkeys performed a delayed memory saccade task that included choices between equally or unequally rewarded options. Pulvinar inactivation resulted in a delay of saccade initiation toward memorized contralesional targets but did not affect spatial memory. Furthermore, pulvinar inactivation caused a pronounced choice bias toward the ipsilesional hemifield when the reward value in the two hemifields was equal. However, this choice bias could be alleviated by placing a high reward target into the contralesional hemifield. The bias was less affected by the manipulation of relative visual saliency between the two competing targets. These results suggest that the dorsal pulvinar is involved in determining the behavioral desirability of movement goals while being less critical for spatial memory and reward processing.

  12. Reduction of interferences in the analysis of Children's Dimetapp using ultraviolet spectroscopy data and target factor analysis

    Science.gov (United States)

    Msimanga, Huggins Z.; Lam, Truong Thach Ho; Latinwo, Nathaniel; Song, Mihyang Kristy; Tavakoli, Newsha

    2018-03-01

    A calibration matrix has been developed and successfully applied to quantify actives in Children's Dimetapp®, a cough mixture whose active components suffer from heavy spectral interference. High-performance liquid chromatography/photodiode array instrument was used to identify the actives and any other UV-detectable excipients that might contribute to interferences. The instrument was also used to obtain reference data on the actives, instead of relying on the manufacturer's claims. Principal component analysis was used during the developmental stages of the calibration matrix to highlight any mismatch between the calibration and sample spectra, making certain that "apples" were not compared with "oranges". The prediction model was finally calculated using target factor analysis and partial least squares regression. In addition to the actives in Children's Dimetapp® (brompheniramine maleate, phenylephrine hydrogen chloride, and dextromethorphan hydrogen bromide), sodium benzoate was identified as the major and FD&C Blue #1, FD&C Red #40, and methyl anthranilate as minor spectral interferences. Model predictions were compared before and after the interferences were included into the calibration matrix. Before including interferences, the following results were obtained: brompheniramine maleate = 481.3 mg L- 1 ± 134% RE; phenylephrine hydrogen chloride = 1041 mg L- 1 ± 107% RE; dextromethorphan hydrogen bromide = 1571 mg L- 1 ± 107% RE, where % RE = percent relative error based on the reference HPLC data. After including interferences, the results were as follows: brompheniramine maleate = 196.3 mg L- 1 ± 4.4% RE; phenylephrine hydrogen chloride = 501.3 mg L- 1 ± 0.10% RE; dextromethorphan hydrogen bromide = 998.7 mg L- 1 ± 1.6% RE as detailed in Table 6.

  13. Fluorescence Imaging Analysis of Upstream Regulators and Downstream Targets of STAT3 in Melanoma Precursor Lesions Obtained from Patients Before and After Systemic Low-Dose Interferon-α Treatment

    Directory of Open Access Journals (Sweden)

    Amanda Pfaff Smith

    2003-01-01

    Full Text Available Atypical nevi are the precursors and risk markers of melanoma. Apart from persistently monitoring these nevocytic lesions and resecting them at the earliest signs of clinical changes, there is as yet no systemic clinical treatment available to interfere with their progression to melanoma. To explore clinical treatments that might interfere with and possibly prevent atypical nevus progression, a previous study documented that 3 months systemic low-dose interferon-α (IFN-α treatment of patients with a clinical history of melanoma and numerous atypical nevi, led to inactivation of the STAT1 and STAT3 transcription factors in atypical nevi. Based upon this finding, we initiated a second study to determine whether systemic low-dose IFN-α treatment also impairs the expression of upstream regulators and downstream targets of STAT1 and STAT3 in atypical nevi. Using cyanine dye-conjugated antibodies, fluorescence imaging analysis revealed expression of JAK2, JNK1, AKT1, NF-κB, and IFN-αβ receptor in benign and atypical nevi, and early- and advanced-stage melanomas. To determine possible changes in the level of expression of these molecules in atypical nevi, excised before and after 3 months of systemic low-dose IFN-α treatment, newly designed optical imaging software was used to quantitate the captured fluorescent hybridization signals on a cell-by-cell basis and across an entire nevus section. The results of this analysis did not provide evidence that systemic low-dose IFN-α treatment alters the level of expression of upstream regulators or downstream targets of STAT1 and STAT3.

  14. Transfusion of pooled buffy coat platelet components prepared with photochemical pathogen inactivation treatment: the euroSPRITE trial

    NARCIS (Netherlands)

    D.J. van Rhenen (Dirk Jan); S. Marblie (Stephane); M. Laforet (Michel); K. Davis (Kathryn); M. Conlan (Maureen); B. Lioure (Bruno); H. Gulliksson (Hans); J.P. Cazenave; P. Metzel (Peyton); D. Pamphilon (Derwood); L. Corash (Laurence); J. Flament (Jocelyne); P. Ljungman (Per); H. Kluter; H. Vermeij (Hans); V. Mayaudon (Veronique); L. Lin (Lily); M.C. Kappers-Klunne (Mies); D. Buchholz (Don); G.E. de Greef (Georgine)

    2003-01-01

    textabstractA nucleic acid-targeted photochemical treatment (PCT) using amotosalen HCl (S-59) and ultraviolet A (UVA) light was developed to inactivate viruses, bacteria, protozoa, and leukocytes in platelet components. We conducted a controlled, randomized, double-blinded trial in thrombocytopenic

  15. The Effect of Campaign-Generated Interpersonal Communication on Campaign-Targeted Health Outcomes: A Meta-Analysis.

    Science.gov (United States)

    Jeong, Michelle; Bae, Rosie Eungyuhl

    2017-06-16

    This study examined the effect of mass media campaign-generated conversations on campaign-targeted health outcomes, via a systematic meta-analysis of 28 studies (including 124 sub-studies and a total of 138,898 participants). The study also conducted a series of moderation analyses to examine the conditions under which interpersonal communication has larger effects on bringing about the desired outcomes. The findings of this meta-analysis indicate that campaign-generated conversations have a positive effect on inducing campaign-targeted outcomes (OR = 1.28) and show that this effect is moderated by health topic addressed by the campaign, the type of outcome being targeted by the campaign, and with whom people converse, along with several other campaign-relevant and study-relevant variables. The implications of these findings for future research are discussed.

  16. Is Angiosome-Targeted Angioplasty Effective for Limb Salvage and Wound Healing in Diabetic Foot? : A Meta-Analysis.

    Science.gov (United States)

    Chae, Kum Ju; Shin, Jin Yong

    2016-01-01

    Given that the efficacy of employing angiosome-targeted angioplasty in the treatment of diabetic foot remains controversial, this study was conducted to examine its efficacy. We performed a systematic literature review and meta-analysis using core databases, extracting the treatment modality of angiosome-targeted angioplasty as the predictor variable, and limb salvage, wound healing, and revision rate as the outcome variables. We used the Newcastle-Ottawa Scale to assess the study quality, along with the Cochrane Risk of Bias Tool. We evaluated publication bias using a funnel plot. The search strategy identified 518 publications. After screening these, we selected four articles for review. The meta-analysis revealed that overall limb salvage and wound healing rates were significantly higher (Odds ratio = 2.209, 3.290, p = 0.001, pdiabetic foot was more effective than nonangiosome-targeted angioplasty with respect to wound healing and limb salvage.

  17. Putative drug and vaccine target protein identification using comparative genomic analysis of KEGG annotated metabolic pathways of Mycoplasma hyopneumoniae.

    Science.gov (United States)

    Damte, Dereje; Suh, Joo-Won; Lee, Seung-Jin; Yohannes, Sileshi Belew; Hossain, Md Akil; Park, Seung-Chun

    2013-07-01

    In the present study, a computational comparative and subtractive genomic/proteomic analysis aimed at the identification of putative therapeutic target and vaccine candidate proteins from Kyoto Encyclopedia of Genes and Genomes (KEGG) annotated metabolic pathways of Mycoplasma hyopneumoniae was performed for drug design and vaccine production pipelines against M.hyopneumoniae. The employed comparative genomic and metabolic pathway analysis with a predefined computational systemic workflow extracted a total of 41 annotated metabolic pathways from KEGG among which five were unique to M. hyopneumoniae. A total of 234 proteins were identified to be involved in these metabolic pathways. Although 125 non homologous and predicted essential proteins were found from the total that could serve as potential drug targets and vaccine candidates, additional prioritizing parameters characterize 21 proteins as vaccine candidate while druggability of each of the identified proteins evaluated by the DrugBank database prioritized 42 proteins suitable for drug targets. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Privacy Policies for Apps Targeted Toward Youth: Descriptive Analysis of Readability

    Science.gov (United States)

    Das, Gitanjali; Cheung, Cynthia; Nebeker, Camille; Bietz, Matthew

    2018-01-01

    Background Due to the growing availability of consumer information, the protection of personal data is of increasing concern. Objective We assessed readability metrics of privacy policies for apps that are either available to or targeted toward youth to inform strategies to educate and protect youth from unintentional sharing of personal data. Methods We reviewed the 1200 highest ranked apps from the Apple and Google Play Stores and systematically selected apps geared toward youth. After applying exclusion criteria, 99 highly ranked apps geared toward minors remained, 64 of which had a privacy policy. We obtained and analyzed these privacy policies using reading grade level (RGL) as a metric. Policies were further compared as a function of app category (free vs paid; entertainment vs social networking vs utility). Results Analysis of privacy policies for these 64 apps revealed an average RGL of 12.78, which is well above the average reading level (8.0) of adults in the United States. There was also a small but statistically significant difference in word count as a function of app category (entertainment: 2546 words, social networking: 3493 words, and utility: 1038 words; P=.02). Conclusions Although users must agree to privacy policies to access digital tools and products, readability analyses suggest that these agreements are not comprehensible to most adults, let alone youth. We propose that stakeholders, including pediatricians and other health care professionals, play a role in educating youth and their guardians about the use of Web-based services and potential privacy risks, including the unintentional sharing of personal data. PMID:29301737

  19. Targeted resequencing and analysis of the Diamond-Blackfan anemia disease locus RPS19.

    Directory of Open Access Journals (Sweden)

    Alvaro Martinez Barrio

    2009-07-01

    Full Text Available The Ribosomal protein S19 gene locus (RPS19 has been linked to two kinds of red cell aplasia, Diamond-Blackfan Anemia (DBA and Transient Erythroblastopenia in Childhood (TEC. Mutations in RPS19 coding sequences have been found in 25% of DBA patients, but not in TEC patients. It has been suggested that non-coding RPS19 sequence variants contribute to the considerable clinical variability in red cell aplasia. We therefore aimed at identifying non-coding variations associated with DBA or TEC phenotypes.We targeted a region of 19'980 bp encompassing the RPS19 gene in a cohort of 89 DBA and TEC patients for resequencing. We provide here a catalog of the considerable, previously unrecognized degree of variation in this region. We identified 73 variations (65 SNPs, 8 indels that all are located outside of the RPS19 open reading frame, and of which 67.1% are classified as novel. We hypothesize that specific alleles in non-coding regions of RPS19 could alter the binding of regulatory proteins or transcription factors. Therefore, we carried out an extensive analysis to identify transcription factor binding sites (TFBS. A series of putative interaction sites coincide with detected variants. Sixteen of the corresponding transcription factors are of particular interest, as they are housekeeping genes or show a direct link to hematopoiesis, tumorigenesis or leukemia (e.g. GATA-1/2, PU.1, MZF-1.Specific alleles at predicted TFBSs may alter the expression of RPS19, modify an important interaction between transcription factors with overlapping TFBS or remove an important stimulus for hematopoiesis. We suggest that the detected interactions are of importance for hematopoiesis and could provide new insights into individual response to treatment.

  20. Global Transcriptomic Analysis of Targeted Silencing of Two Paralogous ACC Oxidase Genes in Banana

    Science.gov (United States)

    Xia, Yan; Kuan, Chi; Chiu, Chien-Hsiang; Chen, Xiao-Jing; Do, Yi-Yin; Huang, Pung-Ling

    2016-01-01

    Among 18 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase homologous genes existing in the banana genome there are two genes, Mh-ACO1 and Mh-ACO2, that participate in banana fruit ripening. To better understand the physiological functions of Mh-ACO1 and Mh-ACO2, two hairpin-type siRNA expression vectors targeting both the Mh-ACO1 and Mh-ACO2 were constructed and incorporated into the banana genome by Agrobacterium-mediated transformation. The generation of Mh-ACO1 and Mh-ACO2 RNAi transgenic banana plants was confirmed by Southern blot analysis. To gain insights into the functional diversity and complexity between Mh-ACO1 and Mh-ACO2, transcriptome sequencing of banana fruits using the Illumina next-generation sequencer was performed. A total of 32,093,976 reads, assembled into 88,031 unigenes for 123,617 transcripts were obtained. Significantly enriched Gene Oncology (GO) terms and the number of differentially expressed genes (DEGs) with GO annotation were ‘catalytic activity’ (1327, 56.4%), ‘heme binding’ (65, 2.76%), ‘tetrapyrrole binding’ (66, 2.81%), and ‘oxidoreductase activity’ (287, 12.21%). Real-time RT-PCR was further performed with mRNAs from both peel and pulp of banana fruits in Mh-ACO1 and Mh-ACO2 RNAi transgenic plants. The results showed that expression levels of genes related to ethylene signaling in ripening banana fruits were strongly influenced by the expression of genes associated with ethylene biosynthesis. PMID:27681726

  1. Functional analysis of TMLH variants and definition of domains required for catalytic activity and mitochondrial targeting.

    Science.gov (United States)

    Monfregola, Jlenia; Cevenini, Armando; Terracciano, Antonio; van Vlies, Naomi; Arbucci, Salvatore; Wanders, Ronald J A; D'Urso, Michele; Vaz, Frédéric M; Ursini, Matilde Valeria

    2005-09-01

    epsilon-N-Trimethyllysine hydroxylase (TMLH) (EC 1.14.11.8) is a non-heme-ferrous iron hydroxylase, Fe(++) and 2-oxoglutarate (2OG) dependent, catalyzing the first of four enzymatic reactions of the highly conserved carnitine biosynthetic pathway. Otherwise from all the other enzymes of carnitine biosynthesis, TMLH was found to be associated to the mitochondrial fraction. We here report molecular cloning of two alternative spliced forms of TMLH, which appear ubiquitously expressed in human adult and fetal tissues. The deduced proteins are designated TMLH-a and TMLH-b, and contain 421 and 399 amino acids, respectively. They share the first N-terminal 332 amino acids, including a mitochondrial targeting signal, but diverge at the C-terminal end. TMLH-a and TMLH-b exogenous expression in COS-1 cells shows that the first 15 amino acids are necessary and sufficient for mitochondrial import. Furthermore, comparative evolutionary analysis of the C-terminal portion of TMLH-a identifies a conserved domain characterized by a key triad of residues, His242-Glu244-His389 predicted to bind 2OG end. This sequence is conserved in the TMLH enzyme from all species but is partially substituted by a unique sequence in the TMLH-b variant. Indeed, TMLH-b is not functional by itself as well as a TMLH-H389L mutant produced by site directed mutagenesis. As great interest, we found that TMLH-b and TMLH-H389L, individually co-expressed with TMLH-a in COS-1 cells, negatively affect TMLH activity. Therefore, our studies on the TMLH alternative form provide relevant novel information, first that the C-terminal region of TMLH contains the main determinants for its enzymatic activity including a key H389 residue, and second that TMLH-b could act as a crucial physiological negative regulator of TMLH. Copyright 2005 Wiley-Liss, Inc.

  2. Quantitative Proteomics Analysis Identifies Mitochondria as Therapeutic Targets of Multidrug-Resistance in Ovarian Cancer

    Science.gov (United States)

    Chen, Xiulan; Wei, Shasha; Ma, Ying; Lu, Jie; Niu, Gang; Xue, Yanhong; Chen, Xiaoyuan; Yang, Fuquan

    2014-01-01

    Doxorubicin is a widely used chemotherapeutic agent for the treatment of a variety of solid tumors. However, resistance to this anticancer drug is a major obstacle to the effective treatment of tumors. As mitochondria play important roles in cell life and death, we anticipate that mitochondria may be related to drug resistance. Here, stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomic strategy was applied to compare mitochondrial protein expression in doxorubicin sensitive OVCAR8 cells and its doxorubicin-resistant variant NCI_ADR/RES cells. A total of 2085 proteins were quantified, of which 122 proteins displayed significant changes in the NCI_ADR/RES cells. These proteins participated in a variety of cell processes including cell apoptosis, substance metabolism, transport, detoxification and drug metabolism. Then qRT-PCR and western blot were applied to validate the differentially expressed proteins quantified by SILAC. Further functional studies with RNAi demonstrated TOP1MT, a mitochondrial protein participated in DNA repair, was involved in doxorubicin resistance in NCI_ADR/RES cells. Besides the proteomic study, electron microscopy and fluorescence analysis also observed that mitochondrial morphology and localization were greatly altered in NCI_ADR/RES cells. Mitochondrial membrane potential was also decreased in NCI_ADR/RES cells. All these results indicate that mitochondrial function is impaired in doxorubicin-resistant cells and mitochondria play an important role in doxorubicin resistance. This research provides some new information about doxorubicin resistance, indicating that mitochondria could be therapeutic targets of doxorubicin resistance in ovarian cancer cells. PMID:25285166

  3. "Slow" Voltage-Dependent Inactivation of CaV2.2 Calcium Channels Is Modulated by the PKC Activator Phorbol 12-Myristate 13-Acetate (PMA.

    Directory of Open Access Journals (Sweden)

    Lei Zhu

    Full Text Available CaV2.2 (N-type voltage-gated calcium channels (Ca2+ channels play key roles in neurons and neuroendocrine cells including the control of cellular excitability, neurotransmitter / hormone secretion, and gene expression. Calcium entry is precisely controlled by channel gating properties including multiple forms of inactivation. "Fast" voltage-dependent inactivation is relatively well-characterized and occurs over the tens-to- hundreds of milliseconds timeframe. Superimposed on this is the molecularly distinct, but poorly understood process of "slow" voltage-dependent inactivation, which develops / recovers over seconds-to-minutes. Protein kinases can modulate "slow" inactivation of sodium channels, but little is known about if/how second messengers control "slow" inactivation of Ca2+ channels. We investigated this using recombinant CaV2.2 channels expressed in HEK293 cells and native CaV2 channels endogenously expressed in adrenal chromaffin cells. The PKC activator phorbol 12-myristate 13-acetate (PMA dramatically prolonged recovery from "slow" inactivation, but an inactive control (4α-PMA had no effect. This effect of PMA was prevented by calphostin C, which targets the C1-domain on PKC, but only partially reduced by inhibitors that target the catalytic domain of PKC. The subtype of the channel β-subunit altered the kinetics of inactivation but not the magnitude of slowing produced by PMA. Intracellular GDP-β-S reduced the effect of PMA suggesting a role for G proteins in modulating "slow" inactivation. We postulate that the kinetics of recovery from "slow" inactivation could provide a molecular memory of recent cellular activity and help control CaV2 channel availability, electrical excitability, and neurotransmission in the seconds-to-minutes timeframe.

  4. EPA’s Non-Targeted Analysis Research Program: Expanding public data resources in support of exposure science

    Science.gov (United States)

    Suspect screening (SSA) and non-targeted analysis (NTA) methods using high-resolution mass spectrometry (HRMS) offer new approaches to efficiently generate exposure data for chemicals in a variety of environmental and biological media. These techniques aid characterization of the...

  5. Target genes prediction and functional analysis of microRNAs differentially expressed in gastric cancer stem cells MKN-45

    Directory of Open Access Journals (Sweden)

    Zohreh Salehi

    2017-01-01

    Conclusions: Bioinformatics analysis such as DAVID database, GO biological process, GO molecular function, Kyoto encyclopedia of genes and genomes pathways, BioCarta pathway, Panther pathway, and Reactome pathway revealed that target genes of differentially expressed miRNAs in gastric CSCs were connected to pivotal biological pathways that involved in cell cycle regulation, stemness properties, and differentiation.

  6. Cost-benefit analysis for biological control programs that target insects pests of eucalypts in urban landscapes of California

    Science.gov (United States)

    T.D. Paine; J.G. Millar; L.M. Hanks; J. Gould; Q. Wang; K. Daane; D.L. Dahlsten; E.G. McPherson

    2015-01-01

    As well as being planted for wind breaks, landscape trees, and fuel wood, eucalypts are also widely used as urban street trees in California. They now are besieged by exotic insect herbivores of four different feeding guilds. The objective of the current analysis was to determine the return on investment from biological control programs that have targeted these pests....

  7. Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy

    DEFF Research Database (Denmark)

    So, Jonathan; Pasculescu, Adrian; Dai, Anna Y.

    2015-01-01

    phosphoproteomics. With these protein interaction maps, we modeled information flow through the networks and identified apoptosis-modifying kinases that are highly connected to regulated substrates downstream of TRAIL. The results of this analysis provide a resource of potential targets for the development of TRAIL...

  8. Long-rod projectiles against oblique targets: analysis and design recommendations

    International Nuclear Information System (INIS)

    Norris, D.M.; McMaster, W.H.; Wilkins, M.L.

    1976-01-01

    Computer calculations provide an understanding of impact phenomena associated with long rod penetrators striking targets at oblique angles. The rod and target material behaviors are described by elastic-plastic work-hardening constitutive models. Ductile fracture is simulated by setting all tensile and shear stresses to zero when the calculated plastic deformation reaches a critical value. The important penetration material properties to defeat a given target are identified. There is no single material property of overriding importance; a combination of properties is required for an efficient penetrator. Experimental results are presented to demonstrate the effects of ductility and toughness on penetration performance. Recommendations for possible improvement are suggested

  9. Analysis of the optical scattering characteristics of different types of space targets

    International Nuclear Information System (INIS)

    Han, Yi; Sun, Huayan; Feng, Jianguang; Li, Liang

    2014-01-01

    This paper mainly focused on the measurement, evaluation and potential identification methods of the unresolved space target's photometric characteristics. The bidirectional reflectance distribution function (BRDF) measurement system was introduced first, and then the measurement error of BRDF and its influence on target's optical cross section (OCS) and magnitude were analyzed. Then, different space targets’ OCS and magnitude changing with different factors, such as surface materials and shapes, flying conditions and working states, were analyzed respectively, and some general inclusions of variation laws were deduced. This research can provide references for future studies on space target classification and identification based on the photometric measurement data. (paper)

  10. Potential actionable targets in appendiceal cancer detected by immunohistochemistry, fluorescent in situ hybridization, and mutational analysis

    Science.gov (United States)

    Millis, Sherri Z.; Kimbrough, Jeffery; Doll, Nancy; Von Hoff, Daniel; Ramanathan, Ramesh K.

    2017-01-01

    Background Appendiceal cancers are rare and consist of carcinoid, mucocele, pseudomyxoma peritonei (PMP), goblet cell carcinoma, lymphoma, and adenocarcinoma histologies. Current treatment involves surgical resection or debulking, but no standard exists for adjuvant chemotherapy or treatment for metastatic disease. Methods Samples were identified from approximately 60,000 global tumors analyzed at a referral molecular profiling CLIA-certified laboratory. A total of 588 samples with appendix primary tumor sites were identified (male/female ratio of 2:3; mean age =55). Sixty-two percent of samples were adenocarcinomas (used for analysis); the rest consisted of 9% goblet cell, 15% mucinous; 6% pseudomyxoma, and less than 5% carcinoids and 2% neuroendocrine. Tests included sequencing [Sanger, next generation sequencing (NGS)], protein expression/immunohistochemistry (IHC), and gene amplification [fluorescent in situ hybridization (FISH) or CISH]. Results Profiling across all appendiceal cancer histological subtypes for IHC revealed: 97% BRCP, 81% MRP1, 81% COX-2, 71% MGMT, 56% TOPO1, 5% PTEN, 52% EGFR, 40% ERCC1, 38% SPARC, 35% PDGFR, 35% TOPO2A, 25% RRM1, 21% TS, 16% cKIT, and 12% for TLE3. NGS revealed mutations in the following genes: 50.4% KRAS, 21.9% P53, 17.6% GNAS, 16.5% SMAD4, 10% APC, 7.5% ATM, 5.5% PIK3CA, 5.0% FBXW7, and 1.8% BRAF. Conclusions Appendiceal cancers show considerable heterogeneity with high levels of drug resistance proteins (BCRP and MRP1), which highlight the difficulty in treating these tumors and suggest an individualized approach to treatment. The incidence of low TS (79%) could be used as a backbone of therapy (using inhibitors such as 5FU/capecitabine or newer agents). Therapeutic options includeTOPO1 inhibitors (irinotecan/topotecan), EGFR inhibitors (erlotinib, cetuximab), PDGFR antagonists (regorafenib, axitinib), MGMT (temozolomide). Clinical trials targeting pathways involving KRAS, p53, GNAS, SMAD4, APC, ATM, PIK3CA, FBXW7, and

  11. [Content analysis of television commercials for snacks and of snack packaging targeted at children].

    Science.gov (United States)

    Akamatsu, Rie

    2010-06-01

    To describe the marketing of snacks and beverages to children in television (TV) commercials and on food packages. Study 1: For 5 weeks from April 1 to May 7, 2007, TV commercials were recorded from one of five channels each week (Nihon, TBS, Fuji, Asahi, and Tokyo). Study 2: The energy values of the products advertised in the TV commercials analyzed in Study 1 were determined, along with whether marketing information (e.g., presents, campaigns, and URLs) was included on the packages. The data were shown in frequency tables, and a chi2 test was conducted to examine the relationship between the energy values of the products (under or over 200 kcal) and descriptions concerning consumption of the products presented in the TV commercials (none, eating alone and eating with others). Five hours and 18 minutes of food commercials and 2 hours and 57 minutes of snack commercials were obtained from the 105 hours of recordings. Of the food commercials, 55.7% were for snacks. Commercials that were repeated or that targeted adults were excluded, leaving 197 commercials for analysis. There were many beverage commercials, most often associating products with mood, such as having fun and good times. No relationship between the energy value of the products (under or over 200 kcal), and the description of consuming the product in the TV commercials (none, eating alone and eating with others) was found (chi2 (2) = 2.2, P = 0.33). A scene showing someone eating alone was the most common depiction for products with energy levels both under and over 200 kcal. The analysis of 164 snack packages showed that most gave URLs. Although the present study had several limitations, such as the relatively short research period, as the first to describe TV commercials for snacks and beverages in Japan it provides new insights. It is now necessary to understand the current state of commercials in other media, and to consider the content of nutrition education for the future, including media literacy

  12. Network analysis of translocated Takahe populations to identify disease surveillance targets.

    Science.gov (United States)

    Grange, Zoë L; VAN Andel, Mary; French, Nigel P; Gartrell, Brett D

    2014-04-01

    Social network analysis is being increasingly used in epidemiology and disease modeling in humans, domestic animals, and wildlife. We investigated this tool in describing a translocation network (area that allows movement of animals between geographically isolated locations) used for the conservation of an endangered flightless rail, the Takahe (Porphyrio hochstetteri). We collated records of Takahe translocations within New Zealand and used social network principles to describe the connectivity of the translocation network. That is, networks were constructed and analyzed using adjacency matrices with values based on the tie weights between nodes. Five annual network matrices were created using the Takahe data set, each incremental year included records of previous years. Weights of movements between connected locations were assigned by the number of Takahe moved. We calculated the number of nodes (i(total)) and the number of ties (t(total)) between the nodes. To quantify the small-world character of the networks, we compared the real networks to random graphs of the equivalent size, weighting, and node strength. Descriptive analysis of cumulative annual Takahe movement networks involved determination of node-level characteristics, including centrality descriptors of relevance to disease modeling such as weighted measures of in degree (k(i)(in)), out degree (k(i)(out)), and betweenness (B(i)). Key players were assigned according to the highest node measure of k(i)(in), k(i)(out), and B(i) per network. Networks increased in size throughout the time frame considered. The network had some degree small-world characteristics. Nodes with the highest cumulative tie weights connecting them were the captive breeding center, the Murchison Mountains and 2 offshore islands. The key player fluctuated between the captive breeding center and the Murchison Mountains. The cumulative networks identified the captive breeding center every year as the hub of the network until the final

  13. Selection of inactivation medium for fungal spores in clinical wastes by supercritical carbon dioxide.

    Science.gov (United States)

    Noman, Efaq; Norulaini Nik Ab Rahman, Nik; Al-Gheethi, Adel; Nagao, Hideyuki; Talip, Balkis A; Ab Kadir, Omar

    2018-05-21

    The present study aimed to select the best medium for inactivation of Aspergillus fumigatus, Aspergillus spp. in section Nigri, A. niger, A. terreus var. terreus, A. tubingensis, Penicillium waksmanii, P. simplicissimum, and Aspergillus sp. strain no. 145 spores in clinical wastes by using supercritical carbon dioxide (SC-CO 2 ). There were three types of solutions used including normal saline, seawater, distilled water, and physiological saline with 1% of methanol; each solution was tested at 5, 10, and 20 mL of the water contents. The experiments were conducted at the optimum operating parameters of supercritical carbon dioxide (30 MPa, 75 °C, 90 min). The results showed that the inactivation rate was more effective in distilled water with the presence of 1% methanol (6 log reductions). Meanwhile, the seawater decreases inactivation rate more than normal saline (4.5 vs. 5.1 log reduction). On the other hand, the experiments performed with different volumes of distilled water (5, 10, and 20 mL) indicated that A. niger spores were completely inactivated with 10 mL of distilled water. The inactivation rate of fungal spores decreased from 6 to 4.5 log as the amount of distilled water increased from 10 to 20 mL. The analysis for the spore morphology of A. fumigatus and Aspergillus spp. in section Nigri using scanning electron microscopy (SEM) has revealed the role of temperature and pressure in the SC-CO 2 in the destruction of the cell walls of the spores. It can be concluded that the distilled water represent the best medium for inactivation of fungal spores in the clinical solid wastes by SC-CO 2 .

  14. Noggin inactivation affects the number and differentiation potential of muscle progenitor cells in vivo

    Science.gov (United States)

    Costamagna, Domiziana; Mommaerts, Hendrik; Sampaolesi, Maurilio; Tylzanowski, Przemko

    2016-01-01

    Inactivation of Noggin, a secreted antagonist of Bone Morphogenetic Proteins (BMPs), in mice leads, among others, to severe malformations of the appendicular skeleton and defective skeletal muscle fibers. To determine the molecular basis of the phenotype, we carried out a histomorphological and molecular analysis of developing muscles Noggin−/− mice. We show that in 18.5 dpc embryos there is a marked reduction in muscle fiber size and a failure of nuclei migration towards the cell membrane. Molecularly, the absence of Noggin results in an increased BMP signaling in muscle tissue as shown by the increase in SMAD1/5/8 phosphorylation, concomitant with the induction of BMP target genes such as Id1, 2, 3 as well as Msx1. Finally, upon removal of Noggin, the number of mesenchymal Pax7+ muscle precursor cells is reduced and they are more prone to differentiate into adipocytes in vitro. Thus, our results highlight the importance of Noggin/BMP balance for myogenic commitment of early fetal progenitor cells. PMID:27573479

  15. Single-cell analysis of targeted transcriptome predicts drug sensitivity of single cells within human myeloma tumors.

    Science.gov (United States)

    Mitra, A K; Mukherjee, U K; Harding, T; Jang, J S; Stessman, H; Li, Y; Abyzov, A; Jen, J; Kumar, S; Rajkumar, V; Van Ness, B

    2016-05-01

    Multiple myeloma (MM) is characterized by significant genetic diversity at subclonal levels that have a defining role in the heterogeneity of tumor progression, clinical aggressiveness and drug sensitivity. Although genome profiling studies have demonstrated heterogeneity in subclonal architecture that may ultimately lead to relapse, a gene expression-based prediction program that can identify, distinguish and quantify drug response in sub-populations within a bulk population of myeloma cells is lacking. In this study, we performed targeted transcriptome analysis on 528 pre-treatment single cells from 11 myeloma cell lines and 418 single cells from 8 drug-naïve MM patients, followed by intensive bioinformatics and statistical analysis for prediction of proteasome inhibitor sensitivity in individual cells. Using our previously reported drug response gene expression profile signature at the single-cell level, we developed an R Statistical analysis package available at https://github.com/bvnlabSCATTome, SCATTome (single-cell analysis of targeted transcriptome), that restructures the data obtained from Fluidigm single-cell quantitative real-time-PCR analysis run, filters missing data, performs scaling of filtered data, builds classification models and predicts drug response of individual cells based on targeted transcriptome using an assortment of machine learning methods. Application of SCATT should contribute to clinically relevant analysis of intratumor heterogeneity, and better inform drug choices based on subclonal cellular responses.

  16. Chlorine inactivation of Tubifex tubifex in drinking water and the synergistic effect of sequential inactivation with UV irradiation and chlorine.

    Science.gov (United States)

    Nie, Xiao-Bao; Li, Zhi-Hong; Long, Yuan-Nan; He, Pan-Pan; Xu, Chao

    2017-06-01

    The inactivation of Tubifex tubifex is important to prevent contamination of drinking water. Chlorine is a widely-used disinfectant and the key factor in the inactivation of T. tubifex. This study investigated the inactivation kinetics of chlorine on T. tubifex and the synergistic effect of the sequential use of chlorine and UV irradiation. The experimental results indicated that the Ct (concentration × time reaction ) concept could be used to evaluate the inactivation kinetics of T. tubifex with chlorine, thus allowing for the use of a simpler Ct approach for the assessment of T. tubifex chlorine inactivation requirements. The inactivation kinetics of T. tubifex by chlorine was found to be well-fitted to a delayed pseudo first-order Chick-Watson expression. Sequential experiments revealed that UV irradiation and chlorine worked synergistically to effectively inactivate T. tubifex as a result of the decreased activation energy, E a , induced by primary UV irradiation. Furthermore, the inactivation effectiveness of T. tubifex by chlorine was found to be affected by several drinking water quality parameters including pH, turbidity, and chemical oxygen demand with potassium permanganate (COD Mn ) concentration. High pH exhibited pronounced inactivation effectiveness and the decrease in turbidity and COD Mn concentrations contributed to the inactivation of T. tubifex. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Factor Analysis of Therapist-Identified Treatment Targets in Community-Based Children's Mental Health.

    Science.gov (United States)

    Love, Allison R; Okado, Izumi; Orimoto, Trina E; Mueller, Charles W

    2018-01-01

    The present study used exploratory and confirmatory factor analyses to identify underlying latent factors affecting variation in community therapists' endorsement of treatment targets. As part of a statewide practice management program, therapist completed monthly reports of treatment targets (up to 10 per month) for a sample of youth (n = 790) receiving intensive in-home therapy. Nearly 75 % of youth were diagnosed with multiple co-occurring disorders. Five factors emerged: Disinhibition, Societal Rules Evasion, Social Engagement Deficits, Emotional Distress, and Management of Biodevelopmental Outcomes. Using logistic regression, primary diagnosis predicted therapist selection of Disinhibition and Emotional Distress targets. Client age predicted endorsement of Societal Rules Evasion targets. Practice-to-research implications are discussed.

  18. Analysis on Target Detection and Classification in LTE Based Passive Forward Scattering Radar

    OpenAIRE

    Raja Syamsul Azmir Raja Abdullah; Noor Hafizah Abdul Aziz; Nur Emileen Abdul Rashid; Asem Ahmad Salah; Fazirulhisyam Hashim

    2016-01-01

    The passive bistatic radar (PBR) system can utilize the illuminator of opportunity to enhance radar capability. By utilizing the forward scattering technique and procedure into the specific mode of PBR can provide an improvement in target detection and classification. The system is known as passive Forward Scattering Radar (FSR). The passive FSR system can exploit the peculiar advantage of the enhancement in forward scatter radar cross section (FSRCS) for target detection. Thus, the aim of th...

  19. An analysis of Chinas CO2 emission peaking target and pathways

    OpenAIRE

    He, Jian-Kun

    2017-01-01

    China has set the goal for its CO2 emissions to peak around 2030, which is not only a strategic decision coordinating domestic sustainable development and global climate change mitigation but also an overarching target and a key point of action for Chinas resource conservation, environmental protection, shift in economic development patterns, and CO2 emission reduction to avoid climate change. The development stage where China maps out the CO2 emission peak target is earlier than that of the ...

  20. General Approach to Identifying Potential Targets for Cancer Imaging by Integrated Bioinformatics Analysis of Publicly Available Genomic Profiles

    Directory of Open Access Journals (Sweden)

    Yongliang Yang

    2011-03-01

    Full Text Available Molecular imaging has moved to the forefront of drug development and biomedical research. The identification of appropriate imaging targets has become the touchstone for the accurate diagnosis and prognosis of human cancer. Particularly, cell surface- or membrane-bound proteins are attractive imaging targets for their aberrant expression, easily accessible location, and unique biochemical functions in tumor cells. Previously, we published a literature mining of potential targets for our in-house enzyme-mediated cancer imaging and therapy technology. Here we present a simple and integrated bioinformatics analysis approach that assembles a public cancer microarray database with a pathway knowledge base for ascertaining and prioritizing upregulated genes encoding cell surface- or membrane-bound proteins, which could serve imaging targets. As examples, we obtained lists of potential hits for six common and lethal human tumors in the prostate, breast, lung, colon, ovary, and pancreas. As control tests, a number of well-known cancer imaging targets were detected and confirmed by our study. Further, by consulting gene-disease and protein-disease databases, we suggest a number of significantly upregulated genes as promising imaging targets, including cell surface-associated mucin-1, prostate-specific membrane antigen, hepsin, urokinase plasminogen activator receptor, and folate receptors. By integrating pathway analysis, we are able to organize and map “focused” interaction networks derived from significantly dysregulated entity pairs to reflect important cellular functions in disease processes. We provide herein an example of identifying a tumor cell growth and proliferation subnetwork for prostate cancer. This systematic mining approach can be broadly applied to identify imaging or therapeutic targets for other human diseases.

  1. Particle-induced X-ray emission: thick-target analysis of inorganic materials in the determination of light elements

    International Nuclear Information System (INIS)

    Perez-Arantegui, J.; Castillo, J.R.; Querre, G.

    1994-01-01

    Particle-induced X-ray emission (PIXE) has been applied to the analysis of inorganic materials to determine some elements with Z < 27: Na, Mg, Al, Si, K, Ca, Ti, Mn and Fe, in thick-target analysis. A PIXE method has been developed for the analysis of geological materials, ceramics and pottery. Work has been carried out with an ion beam analytical system, using a low particle beam energy. Relative sensitivity, detection limits, reproducibility and accuracy of the method were calculated based on the analysis of geological standard materials (river sediments, argillaceous limestone, basalt, diorite and granite). Analysis using PIXE offers a number of advantages, such as short analysis time, multi-elemental and nondestructive determinations, and the results are similar to those obtained with other instrumental techniques of analysis. (Author)

  2. FEA Analysis of AP-0 Target Hall Collection Lens (Current Design)

    International Nuclear Information System (INIS)

    Hurh, P.G.; Tang, Z.

    2001-01-01

    The AP-0 Target Hall Collection Lens is a pulsed device which focuses anti-protons just downstream of the Target. Since the angles at which the anti-protons depart the Target can be quite large, a very high focusing strength is required to maximize anti-proton capture into the downstream Debuncher Ring. The current design of the Collection Lens was designed to operate with a focusing gradient of 1,000 T/m. However, multiple failures of early devices resulted in lowering the normal operating gradient to about 750 T/m. At this gradient, the Lens design fares much better, lasting several million pulses, but ultimately still fails. A Finite Element Analysis (FEA) has been performed on this Collection Lens design to help determine the cause and/or nature of the failures. The Collection Lens magnetic field is created by passing high current through a central conductor cylinder. A uniform current distribution through the cylinder will create a tangential or azimuthal magnetic field that varies linearly from zero at the center of the cylinder to a maximum at the outer surface of the cylinder. Anti-proton particles passing through this cylinder (along the longitudinal direction) will see an inward focusing kick back toward the center of the cylinder proportional to the magnetic field strength. For the current Lens design a gradient of 1,000 T/m requires a current of about 580,000 amps. Since the DC power and cooling requirements would be prohibitive, the Lens is operated in a pulsed mode. Each pulse is half sine wave in shape with a pulse duration of about 350 microseconds. Because of the skin effect, the most uniform current density actually occurs about two-thirds of the way through the pulse. This means that the maximum current of the pulse is actually higher than that required in the DC case (about 670,000 amps). Since the beam must pass through the central conductor cylinder it must be made of a conducting material that is also very 'transparent' to the beam. For the

  3. Anomalies in target-controlled infusion: an analysis after 20 years of clinical use.

    Science.gov (United States)

    Engbers, F H M; Dahan, A

    2018-05-01

    Although target-controlled infusion has been in use for more than two decades, its benefits are being obscured by anomalies in clinical practice caused by a number of important problems. These include: a variety of pharmacokinetic models available in open target-controlled infusion systems, which often confuse the user; the extrapolation of anthropomorphic data which provokes anomalous adjustments of dosing by such systems; and the uncertainty of regulatory requirements for the application of target-controlled infusion which causes uncontrolled exploitation of drugs and pharmacokinetic models in target-controlled infusion devices. Comparison of performance of pharmacokinetic models is complex and mostly inconclusive. However, a specific behaviour of a model in a target-controlled infusion system that is neither intended nor supported by scientific data can be considered an artefact or anomaly. Several of these anomalies can be identified in the current commercially available target-controlled infusion systems and are discussed in this review. © 2018 The Association of Anaesthetists of Great Britain and Ireland.

  4. Analysis and modeling of localized heat generation by tumor-targeted nanoparticles (Monte Carlo methods)

    Science.gov (United States)

    Sanattalab, Ehsan; SalmanOgli, Ahmad; Piskin, Erhan

    2016-04-01

    We investigated the tumor-targeted nanoparticles that influence heat generation. We suppose that all nanoparticles are fully functionalized and can find the target using active targeting methods. Unlike the commonly used methods, such as chemotherapy and radiotherapy, the treatment procedure proposed in this study is purely noninvasive, which is considered to be a significant merit. It is found that the localized heat generation due to targeted nanoparticles is significantly higher than other areas. By engineering the optical properties of nanoparticles, including scattering, absorption coefficients, and asymmetry factor (cosine scattering angle), the heat generated in the tumor's area reaches to such critical state that can burn the targeted tumor. The amount of heat generated by inserting smart agents, due to the surface Plasmon resonance, will be remarkably high. The light-matter interactions and trajectory of incident photon upon targeted tissues are simulated by MIE theory and Monte Carlo method, respectively. Monte Carlo method is a statistical one by which we can accurately probe the photon trajectories into a simulation area.

  5. Analysis of the role of homology arms in gene-targeting vectors in human cells.

    Directory of Open Access Journals (Sweden)

    Ayako Ishii

    Full Text Available Random integration of targeting vectors into the genome is the primary obstacle in human somatic cell gene targeting. Non-homologous end-joining (NHEJ, a major pathway for repairing DNA double-strand breaks, is thought to be responsible for most random integration events; however, absence of DNA ligase IV (LIG4, the critical NHEJ ligase, does not significantly reduce random integration frequency of targeting vector in human cells, indicating robust integration events occurring via a LIG4-independent mechanism. To gain insights into the mechanism and robustness of LIG4-independent random integration, we employed various types of targeting vectors to examine their integration frequencies in LIG4-proficient and deficient human cell lines. We find that the integration frequency of targeting vector correlates well with the length of homology arms and with the amount of repetitive DNA sequences, especially SINEs, present in the arms. This correlation was prominent in LIG4-deficient cells, but was also seen in LIG4-proficient cells, thus providing evidence that LIG4-independent random integration occurs frequently even when NHEJ is functionally normal. Our results collectively suggest that random integration frequency of conventional targeting vectors is substantially influenced by homology arms, which typically harbor repetitive DNA sequences that serve to facilitate LIG4-independent random integration in human cells, regardless of the presence or absence of functional NHEJ.

  6. Technical report on analysis and purification of used O-18 cyclotron target water

    International Nuclear Information System (INIS)

    Kim, T. S.; Jeong, D. Y.; Kim, J. W.; Ko, K. H.; Lim, K; Kim, C. J.; Park, K. B.

    2004-01-01

    F-18-labeled 2-[ 18 F]fluoro-deoxy-glucose( 18 F-FDG), which is used for PET diagnosis, is generally synthesized by using the nucleophilic substitution method. If 18 O-H 2 O is irradiated by the protons accelerated in a cyclotron, 18F-fluoride is produced by means of nuclear reaction of 18O(p,n)18F. However, 18 O-H 2 O is very expensive and its timely procurement might be difficult because of its frequent world market fluctuations. Therefore, 18 O-H 2 O used for the production of 18 F-FDG should be reused efficiently. When the target 18 O-H 2 O flows the tubes in the synthetic apparatus and ion-exchange resin, it is contaminated by the organic substances such as ethanol, methanol, and acetonitrile, etc. If the recovered target water containing many of these impurities is reused as target water in a cyclotron, abnormal increases of the pressure in the target chamber during irradiation and reduction of the target chamber life-span may occur. As a result, production yield of 18F-fluoride would be decreased, and also the yield of 18 F-FDG. Therefore, organic substances and various metallic ions contained in recovered 18 O-H 2 O must be eliminated prior to its reuse. Moreover, the loss of 18 O-H 2 O during the purification process must be minimized to use the target water economically

  7. [Model and analysis of spectropolarimetric BRDF of painted target based on GA-LM method].

    Science.gov (United States)

    Chen, Chao; Zhao, Yong-Qiang; Luo, Li; Pan, Quan; Cheng, Yong-Mei; Wang, Kai

    2010-03-01

    Models based on microfacet were used to describe spectropolarimetric BRDF (short for bidirectional reflectance distribution function) with experimental data. And the spectropolarimetric BRDF values of targets were measured with the comparison to the standard whiteboard, which was considered as Lambert and had a uniform reflectance rate up to 98% at arbitrary angle of view. And then the relationships between measured spectropolarimetric BRDF values and the angles of view, as well as wavelengths which were in a range of 400-720 nm were analyzed in details. The initial value needed to be input to the LM optimization method was difficult to get and greatly impacted the results. Therefore, optimization approach which combines genetic algorithm and Levenberg-Marquardt (LM) was utilized aiming to retrieve parameters of nonlinear models, and the initial values were obtained using GA approach. Simulated experiments were used to test the efficiency of the adopted optimization method. And the simulated experiment ensures the optimization method to have a good performance and be able to retrieve the parameters of nonlinear model efficiently. The correctness of the models was validated by real outdoor sampled data. The parameters of DoP model retrieved are the refraction index of measured targets. The refraction index of the same color painted target but with different materials was also obtained. Conclusion has been drawn that the refraction index from these two targets are very near and this slight difference could be understood by the difference in the conditions of paint targets' surface, not the material of the targets.

  8. Microarray Gene Expression Analysis to Evaluate Cell Type Specific Expression of Targets Relevant for Immunotherapy of Hematological Malignancies.

    Directory of Open Access Journals (Sweden)

    M J Pont

    Full Text Available Cellular immunotherapy has proven to be effective in the treatment of hematological cancers by donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation and more recently by targeted therapy with chimeric antigen or T-cell receptor-engineered T cells. However, dependent on the tissue distribution of the antigens that are targeted, anti-tumor responses can be accompanied by undesired side effects. Therefore, detailed tissue distribution analysis is essential to estimate potential efficacy and toxicity of candidate targets for immunotherapy of hematological malignancies. We performed microarray gene expression analysis of hematological malignancies of different origins, healthy hematopoietic cells and various non-hematopoietic cell types from organs that are often targeted in detrimental immune responses after allogeneic stem cell transplantation leading to graft-versus-host disease. Non-hematopoietic cells were also cultured in the presence of IFN-γ to analyze gene expression under inflammatory circumstances. Gene expression was investigated by Illumina HT12.0 microarrays and quality control analysis was performed to confirm the cell-type origin and exclude contamination of non-hematopoietic cell samples with peripheral blood cells. Microarray data were validated by quantitative RT-PCR showing strong correlations between both platforms. Detailed gene expression profiles were generated for various minor histocompatibility antigens and B-cell surface antigens to illustrate the value of the microarray dataset to estimate efficacy and toxicity of candidate targets for immunotherapy. In conclusion, our microarray database provides a relevant platform to analyze and select candidate antigens with hematopoietic (lineage-restricted expression as potential targets for immunotherapy of hematological cancers.

  9. Methods for targetted mutagenesis in gram-positive bacteria

    Science.gov (United States)

    Yang, Yunfeng

    2014-05-27

    The present invention provides a method of targeted mutagenesis in Gram-positive bacteria. In particular, the present invention provides a method that effectively integrates a suicide integrative vector into a target gene in the chromosome of a Gram-positive bacterium, resulting in inactivation of the target gene.

  10. Functional inactivation of dorsal medial striatum alters behavioral flexibility and recognition process in mice.

    Science.gov (United States)

    Qiao, Yanhua; Wang, Xingyue; Ma, Lian; Li, Shengguang; Liang, Jing

    2017-10-01

    Deficits in behavioral flexibility and recognition memory are commonly observed in mental illnesses and neurodegenerative diseases. Abnormality of the striatum has been implicated in an association with the pathology of these diseases. However, the exact roles of striatal heterogeneous structures in these cognitive functions are still unknown. In the present study, we investigated the effects of suppressing neuronal activity in the dorsomedial striatum (DMStr) and nucleus accumbens core (NAcC) on reversal learning and novelty recognition in mice. In addition, the locomotor activity, anxiety-like behavior and social interaction were analyzed. Neuronal inactivation was performed by expressing lentivirus-mediated tetanus toxin (TeNT) in the target regions. The results showed that reversal learning was facilitated by neuronal inactivation in the DMStr but not the NAcC, which was attributable to accelerated extinction of acquired strategy but not to impaired memory retention. Furthermore, mice with NAcC inactivation spent more time exploring a novel object than a familiar one, comparable to control mice. In contrast, mice with DMStr inactivation exhibited no preference to a novel environment during the novel object or place recognition test. The DMStr mice also exhibited decreased anxiety level. No phenotypic effect was observed in the locomotion or social interaction in mice with either DMStr or NAcC inactivation. Altogether, these findings suggest that the DMStr but not the ventral area of the striatum plays a crucial role in learning and memory by coordinating spatial exploration as well as mediating information updating. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Radiation inactivation of multimeric enzymes: application to subunit interactions of adenylate cyclase

    International Nuclear Information System (INIS)

    Verkman, A.S.; Skorecki, K.L.; Ausiello, D.A.

    1986-01-01

    Radiation inactivation has been applied extensively to determine the molecular weight of soluble enzyme and receptor systems from the slope of a linear ln (activity) vs. dose curve. Complex nonlinear inactivation curves are predicted for multimeric enzyme systems, composed of distinct subunits in equilibrium with multimeric complexes. For the system A1 + A2----A1A2, with an active A1A2 complex (associative model), the ln (activity) vs. dose curve is linear for high dissociation constant, K. If a monomer, A1, has all the enzyme activity (dissociative model), the ln (activity) vs. dose curve has an activation hump at low radiation dose if the inactive subunit, A2, has a higher molecular weight than A1 and has upward concavity when A2 is smaller than A1. In general, a radiation inactivation model for a multistep mechanism for enzyme activation fulfills the characteristics of an associative or dissociative model if the reaction step forming active enzyme is an associative or dissociative reaction. Target theory gives the molecular weight of the active enzyme subunit or complex from the limiting slope of the ln (activity) vs. dose curve at high radiation dose. If energy transfer occurs among subunits in the multimer, the ln (activity) vs. dose curve is linear for a single active component and is concave upward for two or more active components. The use of radiation inactivation as a method to determine enzyme size and multimeric subunit assembly is discussed with specific application to the hormone-sensitive adenylate cyclase system. It is shown that the complex inactivation curves presented in the accompanying paper can be used select the best mechanism out of a series of seven proposed mechanisms for the activation of adenylate cyclase by hormone

  12. Differential effects of parietal and frontal inactivations on reaction times distributions in a visual search task

    Directory of Open Access Journals (Sweden)

    Claire eWardak

    2012-06-01

    Full Text Available The posterior parietal cortex participates to numerous cognitive functions, from perceptual to attentional and decisional processes. However, the same functions have also been attributed to the frontal cortex. We previously conducted a series of reversible inactivations of the lateral intraparietal area (LIP and of the frontal eye field (FEF in the monkey which showed impairments in covert visual search performance, characterized mainly by an increase in the mean reaction time (RT necessary to detect a contralesional target. Only subtle differences were observed between the inactivation effects in both areas. In particular, the magnitude of the deficit was dependant of search task difficulty for LIP, but not for FEF.In the present study, we re-examine these data in order to try to dissociate the specific involvement of these two regions, by considering the entire RT distribution instead of mean RT. We use the LATER model to help us interpret the effects of the inactivations with regard to information accumulation rate and decision processes. We show that: 1 different search strategies can be used by monkeys to perform visual search, either by processing the visual scene in parallel, or by combining parallel and serial processes; 2 LIP and FEF inactivations have very different effects on the RT distributions in the two monkeys. Although our results are not conclusive with regards to the exact functional mechanisms affected by the inactivations, the effects we observe on RT distributions could be accounted by an involvement of LIP in saliency representation or decision-making, and an involvement of FEF in attentional shifts and perception. Finally, we observe that the use of the LATER model is limited in the context of a visual search as it cannot fit all the behavioural strategies encountered. We propose that the diversity in search strategies observed in our monkeys also exists in individual human subjects and should be considered in future

  13. Improved techniques for the analysis of experiments with polarized targets. [1 to 2 GeV/c, polarization

    Energy Technology Data Exchange (ETDEWEB)

    Barrelet, E.

    1975-06-01

    An experiment was performed at the Bevatron to measure the polarization in the reaction ..pi../sup -/p ..-->.. ..pi../sup 0/n from a polarized target, at beam momenta between 1 and 2 GeV/c. Concentration is placed on the original aspects of our analysis, in particular: the geometrical reconstruction of the elastic events; the use of the high analyzing power of the reaction studied to probe the polarization of the target in magnitude and distribution; a study of the statistical estimation of the polarization parameter; a detailed study of the quasielastic background. (JFP)

  14. Predicting Bacillus coagulans spores inactivation in tomato pulp under nonisothermal heat treatments.

    Science.gov (United States)

    Zimmermann, Morgana; Longhi, Daniel A; Schaffner, Donald W; Aragão, Gláucia M F

    2014-05-01

    The knowledge and understanding of Bacillus coagulans inactivation during a thermal treatment in tomato pulp, as well as the influence of temperature variation during thermal processes are essential for design, calculation, and optimization of the process. The aims of this work were to predict B. coagulans spores inactivation in tomato pulp under varying time-temperature profiles with Gompertz-inspired inactivation model and to validate the model's predictions by comparing the predicted values with experimental data. B. coagulans spores in pH 4.3 tomato pulp at 4 °Brix were sealed in capillary glass tubes and heated in thermostatically controlled circulating oil baths. Seven different nonisothermal profiles in the range from 95 to 105 °C were studied. Predicted inactivation kinetics showed similar behavior to experimentally observed inactivation curves when the samples were exposed to temperatures in the upper range of this study (99 to 105 °C). Profiles that resulted in less accurate predictions were those where the range of temperatures analyzed were comparatively lower (inactivation profiles starting at 95 °C). The link between fail prediction and both lower starting temperature and magnitude of the temperature shift suggests some chemical or biological mechanism at work. Statistical analysis showed that overall model predictions were acceptable, with bias factors from 0.781 to 1.012, and accuracy factors from 1.049 to 1.351, and confirm that the models used were adequate to estimate B. coagulans spores inactivation under fluctuating temperature conditions in the range from 95 to 105 °C. How can we estimate Bacillus coagulans inactivation during sudden temperature shifts in heat processing? This article provides a validated model that can be used to predict B. coagulans under changing temperature conditions. B. coagulans is a spore-forming bacillus that spoils acidified food products. The mathematical model developed here can be used to predict the spoilage

  15. Effective Thermal Inactivation of the Spores of Bacillus cereus Biofilms Using Microwave.

    Science.gov (United States)

    Park, Hyong Seok; Yang, Jungwoo; Choi, Hee Jung; Kim, Kyoung Heon

    2017-07-28

    Microwave sterilization was performed to inactivate the spores of biofilms of Bacillus cereus involved in foodborne illness. The sterilization conditions, such as the amount of water and the operating temperature and treatment time, were optimized using statistical analysis based on 15 runs of experimental results designed by the Box-Behnken method. Statistical analysis showed that the optimal conditions for the inactivation of B. cereus biofilms were 14 ml of water, 108°C of temperature, and 15 min of treatment time. Interestingly, response surface plots showed that the amount of water is the most important factor for microwave sterilization under the present conditions. Complete inactivation by microwaves was achieved in 5 min, and the inactivation efficiency by microwave was obviously higher than that by conventional steam autoclave. Finally, confocal laser scanning microscopy images showed that the principal effect of microwave treatment was cell membrane disruption. Thus, this study can contribute to the development of a process to control food-associated pathogens.

  16. Bovine intestinal bacteria inactivate and degrade ceftiofur and ceftriaxone with multiple beta-lactamases.

    Science.gov (United States)

    Wagner, R Doug; Johnson, Shemedia J; Cerniglia, Carl E; Erickson, Bruce D

    2011-11-01

    The veterinary cephalosporin drug ceftiofur is rapidly degraded in the bovine intestinal tract. A cylinder-plate assay was used to detect microbiologically active ceftiofur, and high-performance liquid chromatography-mass spectrometry analysis was used to quantify the amount of ceftiofur remaining after incubation with bovine intestinal anaerobic bacteria, which were isolated from colon contents or feces from 8 cattle. Ninety-six percent of the isolates were able to inactivate ceftiofur to some degree, and 54% actually degraded the drug. None of 9 fungal isolates inactivated or degraded ceftiofur. Facultative and obligate anaerobic bacterial species that inactivated or degraded ceftiofur were identified with Vitek and Biolog systems, respectively. A subset of ceftiofur degraders also degraded the chemically similar drug ceftriaxone. Most of the species of bacteria that degraded ceftiofur belonged to the genera Bacillus and Bacteroides. PCR analysis of bacterial DNA detected specific β-lactamase genes. Bacillus cereus and B. mycoides isolates produced extended-spectrum β-lactamases and metallo-β-lactamases. Seven isolates of Bacteroides spp. produced multiple β-lactamases, including possibly CepA, and metallo-β-lactamases. Isolates of Eubacterium biforme, Bifidobacterium breve, and several Clostridium spp. also produced ceftiofur-degrading β-lactamases. An agar gel overlay technique on isoelectric focusing separations of bacterial lysates showed that β-lactamase enzymes were sufficient to degrade ceftiofur. These results suggest that ceftiofur is inactivated nonenzymatically and degraded enzymatically by multiple β-lactamases from bacteria in the large intestines of cattle.

  17. Bovine Intestinal Bacteria Inactivate and Degrade Ceftiofur and Ceftriaxone with Multiple β-Lactamases▿

    Science.gov (United States)

    Wagner, R. Doug; Johnson, Shemedia J.; Cerniglia, Carl E.; Erickson, Bruce D.

    2011-01-01

    The veterinary cephalosporin drug ceftiofur is rapidly degraded in the bovine intestinal tract. A cylinder-plate assay was used to detect microbiologically active ceftiofur, and high-performance liquid chromatography-mass spectrometry analysis was used to quantify the amount of ceftiofur remaining after incubation with bovine intestinal anaerobic bacteria, which were isolated from colon contents or feces from 8 cattle. Ninety-six percent of the isolates were able to inactivate ceftiofur to some degree, and 54% actually degraded the drug. None of 9 fungal isolates inactivated or degraded ceftiofur. Facultative and obligate anaerobic bacterial species that inactivated or degraded ceftiofur were identified with Vitek and Biolog systems, respectively. A subset of ceftiofur degraders also degraded the chemically similar drug ceftriaxone. Most of the species of bacteria that degraded ceftiofur belonged to the genera Bacillus and Bacteroides. PCR analysis of bacterial DNA detected specific β-lactamase genes. Bacillus cereus and B. mycoides isolates produced extended-spectrum β-lactamases and metallo-β-lactamases. Seven isolates of Bacteroides spp. produced multiple β-lactamases, including possibly CepA, and metallo-β-lactamases. Isolates of Eubacterium biforme, Bifidobacterium breve, and several Clostridium spp. also produced ceftiofur-degrading β-lactamases. An agar gel overlay technique on isoelectric focusing separations of bacterial lysates showed that β-lactamase enzymes were sufficient to degrade ceftiofur. These results suggest that ceftiofur is inactivated nonenzymatically and degraded enzymatically by multiple β-lactamases from bacteria in the large intestines of cattle. PMID:21876048

  18. Low carbon and clean energy scenarios for India: Analysis of targets approach

    International Nuclear Information System (INIS)

    Shukla, Priyadarshi R.; Chaturvedi, Vaibhav

    2012-01-01

    Low carbon energy technologies are of increasing importance to India for reducing emissions and diversifying its energy supply mix. Using GCAM, an integrated assessment model, this paper analyzes a targets approach for pushing solar, wind, and nuclear technologies in the Indian electricity generation sector from 2005 to 2095. Targets for these technologies have been constructed on the basis of Indian government documents, policy announcements, and expert opinions. Different targets have been set for the reference scenario and the carbon price scenario. In the reference scenario, wind and nuclear technologies exceed respective targets in the long run without any subsidy push, while solar energy requires subsidy push throughout the century in order to meet its high targets. In the short run, nuclear energy also requires significant subsidy, including a much higher initial subsidy relative to solar power, which is a result of its higher targets. Under a carbon price scenario, the carbon price drives the penetration of these technologies. Still, subsidy is required — especially in the short run when the carbon price is low. We also found that pushing solar, wind, and nuclear technologies leads to a decrease in share of CCS under the carbon price scenario and biomass under both the reference and carbon price scenarios. This is because low carbon technologies compete among themselves and substitute each other, thereby enhancing the need for subsidy or carbon price, highlighting that proposed targets are not set at efficient levels. In light of contemporary debate on external costs of nuclear energy, we also assess the sensitivity of the results to nuclear technology cost. We find that higher cost significantly decreases the share of nuclear power under both the reference and carbon price scenarios.

  19. X Inactivation and Progenitor Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ruben Agrelo

    2011-04-01

    Full Text Available In mammals, silencing of one of the two X chromosomes is necessary to achieve dosage compensation. The 17 kb non-coding RNA called Xist triggers X inactivation. Gene silencing by Xist can only be achieved in certain contexts such as in cells of the early embryo and in certain hematopoietic progenitors where silencing factors are present. Moreover, these epigenetic contexts are maintained in cancer progenitors in which SATB1 has been identified as a factor related to Xist-mediated chromosome silencing.

  20. Interferometric analysis of laboratory photoionized plasmas utilizing supersonic gas jet targets.

    Science.gov (United States)

    Swanson, Kyle James; Ivanov, Vladimir; Mancini, Roberto; Mayes, Daniel C.

    2018-06-01

    Photoionized plasmas are an important component of active galactic nuclei, x-ray binary systems and other astrophysical objects. Laboratory produced photoionized plasmas have mainly been studied at large scale facilities, due to the need for high intensity broadband x-ray flux. Using supersonic gas jets as targets has allowed university scale pulsed power generators to begin similar research. The two main advantages of this approach with supersonic gas jets include: possibility of a closer location to the x-ray source and no attenuation related to material used for containment and or tamping. Due to these factors, this experimental platform creates a laboratory environment that more closely resembles astrophysical environments. This system was developed at the Nevada Terawatt Facility using the 1 MA pulsed power generator Zebra. Neon, argon, and nitrogen supersonic gas jets are produced approximately 7-8mm from the z-pinch axis. The high intensity broadband x-ray flux produced by the collapse of the z-pinch wire array implosion irradiates the gas jet. Cylindrical wire arrays are made with 4 and 8 gold 10µm thick wire. The z-pinch radiates approximately 12-16kj of x-ray energy, with x-ray photons under 1Kev in energy. The photoionized plasma is measured via x-ray absorption spectroscopy and interferometry. A Mach-Zehnder interferometer is used to the measure neutral density of the jet prior to the zebra shot at a wavelength of 266 nm. A dual channel air-wedge shearing interferometer is used to measure electron density of the ionized gas jet during the shot, at wavelengths of 532nm and 266nm. Using a newly developed interferometric analysis tool, average ionization state maps of the plasma can be calculated. Interferometry for nitrogen and argon show an average ionization state in the range of 3-8. Preliminary x-ray absorption spectroscopy collected show neon absorption lines. This work was sponsored in part by DOE Office of Science Grant DE-SC0014451.

  1. Targeted agents for patients with advanced/metastatic pancreatic cancer: A protocol for systematic review and network meta-analysis.

    Science.gov (United States)

    Di, Baoshan; Pan, Bei; Ge, Long; Ma, Jichun; Wu, Yiting; Guo, Tiankang

    2018-03-01

    Pancreatic cancer (PC) is a devastating malignant tumor. Although surgical resection may offer a good prognosis and prolong survival, approximately 80% patients with PC are always diagnosed as unresectable tumor. National Comprehensive Cancer Network's (NCCN) recommended gemcitabine-based chemotherapy as efficient treatment. While, according to recent studies, targeted agents might be a better available option for advanced or metastatic pancreatic cancer patients. The aim of this systematic review and network meta-analysis will be to examine the differences of different targeted interventions for advanced/metastatic PC patients. We will conduct this systematic review and network meta-analysis using Bayesian method and according to Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) statement. To identify relevant studies, 6 electronic databases including PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of science, CNKI (Chinese National Knowledge Infrastructure), and CBM (Chinese Biological Medical Database) will be searched. The risk of bias in included randomized controlled trials (RCTs) will be assessed using the Cochrane Handbook version 5.1.0. And we will use GRADE approach to assess the quality of evidence from network meta-analysis. Data will be analyzed using R 3.4.1 software. To the best of our knowledge, this systematic review and network meta-analysis will firstly use both direct and indirect evidence to compare the differences of different targeted agents and targeted agents plus chemotherapy for advanced/metastatic pancreatic cancer patients. This is a protocol of systematic review and meta-analysis, so the ethical approval and patient consent are not required. We will disseminate the results of this review by submitting to a peer-reviewed journal.

  2. Fuel cell and hydrogen R and D targets and funding : a comparative analysis

    International Nuclear Information System (INIS)

    Adamson, K.A.; Jollie, D.; Baker, A.

    2005-01-01

    Substantial research and development is needed if fuel cells and hydrogen are to become a mass market reality. Setting research and development targets are central to the long term development of the market. An overview of fuel cell research in the United States, the European Union, and parts of Asia was presented. Research and development targets were analyzed, as well as funding levels for fuel cells and hydrogen. The time frames of targets were considered, as well as the levels of ambition and overall program goals of various countries. Funding barriers and challenges were also considered. It was noted that some governments, such as Japan and Korea, have set a number of very ambitious, highly focused long term targets with substantial funding. The European Union has taken a more integrated approach, wrapping fundamental research and development into large integrated projects which run in combination with a number of other market aspects, such as public acceptance and roadmapping. The United States has a number of long term programmes and targets, but levels of funding are set annually with the passing of each year's Fiscal Budget. The overall goal of the paper was to provide a clearer picture of regional fuel cell research in order to discover areas for potential international collaboration

  3. Microdeletion and microduplication analysis of chinese conotruncal defects patients with targeted array comparative genomic hybridization.

    Directory of Open Access Journals (Sweden)

    Xiaohui Gong

    Full Text Available OBJECTIVE: The current study aimed to develop a reliable targeted array comparative genomic hybridization (aCGH to detect microdeletions and microduplications in congenital conotruncal defects (CTDs, especially on 22q11.2 region, and for some other chromosomal aberrations, such as 5p15-5p, 7q11.23 and 4p16.3. METHODS: Twenty-seven patients with CTDs, including 12 pulmonary atresia (PA, 10 double-outlet right ventricle (DORV, 3 transposition of great arteries (TGA, 1 tetralogy of Fallot (TOF and one ventricular septal defect (VSD, were enrolled in this study and screened for pathogenic copy number variations (CNVs, using Agilent 8 x 15K targeted aCGH. Real-time quantitative polymerase chain reaction (qPCR was performed to test the molecular results of targeted aCGH. RESULTS: Four of 27 patients (14.8% had 22q11.2 CNVs, 1 microdeletion and 3 microduplications. qPCR test confirmed the microdeletion and microduplication detected by the targeted aCGH. CONCLUSION: Chromosomal abnormalities were a well-known cause of multiple congenital anomalies (MCA. This aCGH using arrays with high-density coverage in the targeted regions can detect genomic imbalances including 22q11.2 and other 10 kinds CNVs effectively and quickly. This approach has the potential to be applied to detect aneuploidy and common microdeletion/microduplication syndromes on a single microarray.

  4. Discrimination between landmine and mine-like targets using wavelets and spectral analysis

    Directory of Open Access Journals (Sweden)

    Mahmoud A. Mohana

    2013-06-01

    Ground penetrating radar (GPR is a powerful and non-destructive geophysical approach with a wide range of advantages in the field of landmine inspection. In the present paper, we apply different simulation models with Vivaldi antenna and mine-like targets by using the CST Microwave studio program. The field work is carried out by using a GPR device of model SIR 2000 from GSSI (Geophysical Survey Systems Incorporation connected to 900 MHz antenna where the targets were buried in sand soil. Depending on the fact that the receiving powers (reflected, refracted and scattered from the different materials are different, we study the spectral power densities for the received power from the different targets. The techniques used in this study are: direct fast Fourier transform, short time Fourier transform (spectrogram, wavelets transform and denoising techniques. Our results ought to be considered as finger prints for different scanned targets during this work. So we can discriminate between landmines and mine-like targets.

  5. A collection of target mimics for comprehensive analysis of microRNA function in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Marco Todesco

    2010-07-01

    Full Text Available Many targets of plant microRNAs (miRNAs are thought to play important roles in plant physiology and development. However, because plant miRNAs are typically encoded by medium-size gene families, it has often been difficult to assess their precise function. We report the generation of a large-scale collection of knockdowns for Arabidopsis thaliana miRNA families; this has been achieved using artificial miRNA target mimics, a recently developed technique fashioned on an endogenous mechanism of miRNA regulation. Morphological defects in the aerial part were observed for approximately 20% of analyzed families, all of which are deeply conserved in land plants. In addition, we find that non-cleavable mimic sites can confer translational regulation in cis. Phenotypes of plants expressing target mimics directed against miRNAs involved in development were in several cases consistent with previous reports on plants expressing miRNA-resistant forms of individual target genes, indicating that a limited number of targets mediates most effects of these miRNAs. That less conserved miRNAs rarely had obvious effects on plant morphology suggests that most of them do not affect fundamental aspects of development. In addition to insight into modes of miRNA action, this study provides an important resource for the study of miRNA function in plants.

  6. The CERN antiproton target: hydrocode analysis of its core material dynamic response under proton beam impact

    CERN Document Server

    Martin, Claudio Torregrosa; Calviani, Marco; Muñoz-Cobo, José-Luis

    2016-01-01

    Antiprotons are produced at CERN by colliding a 26 GeV/c proton beam with a fixed target made of a 3 mm diameter, 55 mm length iridium core. The inherent characteristics of antiproton production involve extremely high energy depositions inside the target when impacted by each primary proton beam, making it one of the most dynamically demanding among high energy solid targets in the world, with a rise temperature above 2000 {\\deg}C after each pulse impact and successive dynamic pressure waves of the order of GPa's. An optimized redesign of the current target is foreseen for the next 20 years of operation. As a first step in the design procedure, this numerical study delves into the fundamental phenomena present in the target material core under proton pulse impact and subsequent pressure wave propagation by the use of hydrocodes. Three major phenomena have been identified, (i) the dominance of a high frequency radial wave which produces destructive compressive-to-tensile pressure response (ii) The existence of...

  7. Performance Analysis of a Noncontact Plastic Fiber Optical Fiber Displacement Sensor with Compensation of Target Reflectivity

    Directory of Open Access Journals (Sweden)

    Daniele Tosi

    2013-01-01

    Full Text Available An inexpensive fiber-based noncontact distance sensor specific for monitoring short-range displacements in micromachining applications is presented. To keep the overall costs low, the sensor uses plastic optical fibers and an intensiometric approach based on the received light intensity after the reflection from the target whose displacement has to be measured. A suitable target reflectivity compensation technique is implemented to mitigate the effects due to target surface nonuniformity or ageing. The performances of the sensor are first evaluated for different fiber configurations and target reflectivity profiles and positions using a numerical method based on Monte Carlo simulations. Then, experimental validations on a configuration designed to work up to 1.5 mm have been conducted. The results have confirmed the validity of the proposed sensor architecture, which demonstrated excellent compensation capabilities, with errors below 0.04 mm in the (0-1 mm range regardless the color and misalignment of the target.

  8. CERN antiproton target: Hydrocode analysis of its core material dynamic response under proton beam impact

    Directory of Open Access Journals (Sweden)

    Claudio Torregrosa Martin

    2016-07-01

    Full Text Available Antiprotons are produced at CERN by colliding a 26  GeV/c proton beam with a fixed target made of a 3 mm diameter, 55 mm length iridium core. The inherent characteristics of antiproton production involve extremely high energy depositions inside the target when impacted by each primary proton beam, making it one of the most dynamically demanding among high energy solid targets in the world, with a rise temperature above 2000 °C after each pulse impact and successive dynamic pressure waves of the order of GPa’s. An optimized redesign of the current target is foreseen for the next 20 years of operation. As a first step in the design procedure, this numerical study delves into the fundamental phenomena present in the target material core under proton pulse impact and subsequent pressure wave propagation by the use of hydrocodes. Three major phenomena have been identified, (i the dominance of a high frequency radial wave which produces destructive compressive-to-tensile pressure response (ii The existence of end-of-pulse tensile waves and its relevance on the overall response (iii A reduction of 44% in tensile pressure could be obtained by the use of a high density tantalum cladding.

  9. Efficient moving target analysis for inverse synthetic aperture radar images via joint speeded-up robust features and regular moment

    Science.gov (United States)

    Yang, Hongxin; Su, Fulin

    2018-01-01

    We propose a moving target analysis algorithm using speeded-up robust features (SURF) and regular moment in inverse synthetic aperture radar (ISAR) image sequences. In our study, we first extract interest points from ISAR image sequences by SURF. Different from traditional feature point extraction methods, SURF-based feature points are invariant to scattering intensity, target rotation, and image size. Then, we employ a bilateral feature registering model to match these feature points. The feature registering scheme can not only search the isotropic feature points to link the image sequences but also reduce the error matching pairs. After that, the target centroid is detected by regular moment. Consequently, a cost function based on correlation coefficient is adopted to analyze the motion information. Experimental results based on simulated and real data validate the effectiveness and practicability of the proposed method.

  10. Metabolic network analysis-based identification of antimicrobial drug targets in category A bioterrorism agents.

    Directory of Open Access Journals (Sweden)

    Yong-Yeol Ahn

    Full Text Available The 2001 anthrax mail attacks in the United States demonstrated the potential threat of bioterrorism, hence driving the need to develop sophisticated treatment and diagnostic protocols to counter biological warfare. Here, by performing flux balance analyses on the fully-annotated metabolic networks of multiple, whole genome-sequenced bacterial strains, we have identified a large number of metabolic enzymes as potential drug targets for each of the three Category A-designated bioterrorism agents including Bacillus anthracis, Francisella tularensis and Yersinia pestis. Nine metabolic enzymes- belonging to the coenzyme A, folate, phosphatidyl-ethanolamine and nucleic acid pathways common to all strains across the three distinct genera were identified as targets. Antimicrobial agents against some of these enzymes are available. Thus, a combination of cross species-specific antibiotics and common antimicrobials against shared targets may represent a useful combinatorial therapeutic approach against all Category A bioterrorism agents.

  11. Maintenance Therapy in Ovarian Cancer with Targeted Agents Improves PFS and OS: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Xinyu Qian

    Full Text Available Maintenance therapy with targeted agents for prolonging remission for ovarian cancer patients remains controversial. As a result, a meta-analysis was conducted to assess the effectiveness and safety of using maintenance therapy with targeted agents for the treatment of ovarian cancer.From inception to January 2015, we searched for randomized, controlled trials (RCTs using the following databases: PubMed, ScienceDirect, the Cochrane Library, Clinicaltrials.gov and EBSCO. Eligible trials included RCTs that evaluated standard chemotherapy which was either followed or not followed by targeted maintenance in patients with ovarian cancer who had been previously receiving adjunctive treatments, such as cytoreductive surgery and standard chemotherapy. The outcome measures included progression-free survival (PFS, overall survival (OS and incidence of adverse events.A total of 13 RCTs, which were published between 2006 and 2014, were found to be in accordance with our inclusion criteria. The primary meta-analysis indicated that both PFS and OS were statistically and significantly improved in the targeted maintenance therapy group as compared to the control group (PFS: HR = 0.84, 95%CI: 0.75 to 0.95, p = 0.001; OS: HR = 0.91, 95%CI: 0.84 to 0.98, p = 0.02. When taking safety into consideration, the use of targeted agents was significantly correlated with increased risks of fatigue, diarrhea, nausea, vomiting, and hypertension. However, no significant differences were found in incidence rates of abdominal pain, constipation or joint pain.Our results indicate that targeted maintenance therapy clearly improves the survival of ovarian cancer patients but may also increase the incidence of adverse events. Additional randomized, double-blind, placebo-controlled, multicenter investigations will be required on a larger cohort of patients to verify our findings.

  12. Efficacy of targeted therapy for advanced renal cell carcinoma: A systematic review and meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Chao Wei

    Full Text Available ABSTRACT We conducted a systematic review and meta-analysis of the literature on the efficacy of the targeted therapies in the treatment of advanced RCC and, via an indirect comparison, to provide an optimal treatment among these agents. A systematic search of Medline, Scopus, Cochrane Library and Clinical Trials unpublished was performed up to Jan 1, 2015 to identify eligible randomized trials. Outcomes of interest assessing a targeted agent included progression free survival (PFS, overall survival (OS and objective response rate (ORR. Thirty eligible randomized controlled studies, total twentyfourth trails (5110 cases and 4626 controls were identified. Compared with placebo and IFN-α, single vascular epithelial growth factor (receptor tyrosine kinase inhibitor and mammalian target of rapamycin agent (VEGF(r-TKI & mTOR inhibitor were associated with improved PFS, improved OS and higher ORR, respectively. Comparing sorafenib combination vs sorafenib, there was no significant difference with regard to PFS and OS, but with a higher ORR. Comparing single or combination VEGF(r-TKI & mTOR inhibitor vs BEV + IFN-α, there was no significant difference with regard to PFS, OS, or ORR. Our network ITC meta-analysis also indicated a superior PFS of axitinib and everolimus compared to sorafenib. Our data suggest that targeted therapy with VEGF(r-TKI & mTOR inhibitor is associated with superior efficacy for treating advanced RCC with improved PFS, OS and higher ORR compared to placebo and IFN-α. In summary, here we give a comprehensive overview of current targeted therapies of advanced RCC that may provide evidence for the adequate targeted therapy selecting.

  13. Wideband Radar Echo Frequency-domain Simulation and Analysis for High Speed Moving Targets

    Directory of Open Access Journals (Sweden)

    Ning Chao

    2014-04-01

    Full Text Available A frequency-domain method is proposed for wideband radar echo simulation of high-speed moving targets. Based on the physical process of electromagnetic waves observing a moving target, a frequency-domain echo model of wideband radar is constructed, and the block diagram of the radar echo simulation in frequency-domain is presented. Then, the impacts of radial velocity and slant range on the matching filtering of LFM radar are analyzed, and some quantitative conclusions on the shift and expansion of the radar profiles are obtained. Simulation results illustrate the correctness and efficiency of the proposed method.

  14. Hyperspectral target detection analysis of a cluttered scene from a virtual airborne sensor platform using MuSES

    Science.gov (United States)

    Packard, Corey D.; Viola, Timothy S.; Klein, Mark D.

    2017-10-01

    The ability to predict spectral electro-optical (EO) signatures for various targets against realistic, cluttered backgrounds is paramount for rigorous signature evaluation. Knowledge of background and target signatures, including plumes, is essential for a variety of scientific and defense-related applications including contrast analysis, camouflage development, automatic target recognition (ATR) algorithm development and scene material classification. The capability to simulate any desired mission scenario with forecast or historical weather is a tremendous asset for defense agencies, serving as a complement to (or substitute for) target and background signature measurement campaigns. In this paper, a systematic process for the physical temperature and visible-through-infrared radiance prediction of several diverse targets in a cluttered natural environment scene is presented. The ability of a virtual airborne sensor platform to detect and differentiate targets from a cluttered background, from a variety of sensor perspectives and across numerous wavelengths in differing atmospheric conditions, is considered. The process described utilizes the thermal and radiance simulation software MuSES and provides a repeatable, accurate approach for analyzing wavelength-dependent background and target (including plume) signatures in multiple band-integrated wavebands (multispectral) or hyperspectrally. The engineering workflow required to combine 3D geometric descriptions, thermal material properties, natural weather boundary conditions, all modes of heat transfer and spectral surface properties is summarized. This procedure includes geometric scene creation, material and optical property attribution, and transient physical temperature prediction. Radiance renderings, based on ray-tracing and the Sandford-Robertson BRDF model, are coupled with MODTRAN for the inclusion of atmospheric effects. This virtual hyperspectral/multispectral radiance prediction methodology has been

  15. Systems integration of biodefense omics data for analysis of pathogen-host interactions and identification of potential targets.

    Directory of Open Access Journals (Sweden)

    Peter B McGarvey

    2009-09-01

    Full Text Available The NIAID (National Institute for Allergy and Infectious Diseases Biodefense Proteomics program aims to identify targets for potential vaccines, therapeutics, and diagnostics for agents of concern in bioterrorism, including bacterial, parasitic, and viral pathogens. The program includes seven Proteomics Research Centers, generating diverse types of pathogen-host data, including mass spectrometry, microarray transcriptional profiles, protein interactions, protein structures and biological reagents. The Biodefense Resource Center (www.proteomicsresource.org has developed a bioinformatics framework, employing a protein-centric approach to integrate and support mining and analysis of the large and heterogeneous data. Underlying this approach is a data warehouse with comprehensive protein + gene identifier and name mappings and annotations extracted from over 100 molecular databases. Value-added annotations are provided for key proteins from experimental findings using controlled vocabulary. The availability of pathogen and host omics data in an integrated framework allows global analysis of the data and comparisons across different experiments and organisms, as illustrated in several case studies presented here. (1 The identification of a hypothetical protein with differential gene and protein expressions in two host systems (mouse macrophage and human HeLa cells infected by different bacterial (Bacillus anthracis and Salmonella typhimurium and viral (orthopox pathogens suggesting that this protein can be prioritized for additional analysis and functional characterization. (2 The analysis of a vaccinia-human protein interaction network supplemented with protein accumulation levels led to the identification of human Keratin, type II cytoskeletal 4 protein as a potential therapeutic target. (3 Comparison of complete genomes from pathogenic variants coupled with experimental information on complete proteomes allowed the identification and

  16. Factors Affecting Bacterial Inactivation during High Hydrostatic Pressure Processing of Foods: A Review.

    Science.gov (United States)

    Syed, Qamar-Abbas; Buffa, Martin; Guamis, Buenaventura; Saldo, Jordi

    2016-01-01

    Although, the High Hydrostatic Pressure (HHP) technology has been gaining gradual popularity in food industry since last two decades, intensive research is needed to explore the missing information. Bacterial inactivation in food by using HHP applications can be enhanced by getting deeper insights of the process. Some of these aspects have been already studied in detail (like pressure, time, and temperature, etc.), while some others still need to be investigated in more details (like pH, rates of compression, and decompression, etc.). Selection of process parameters is mainly dependent on type of matrix and target bacteria. This intensive review provides comprehensive information about the variety of aspects that can determine the bacterial inactivation potential of HHP process indicating the fields of future research on this subject including pH shifts of the pressure treated samples and critical limits of compression and decompression rates to accelerate the process efficacy.

  17. Inactivation of Parietal Reach Region Affects Reaching But Not Saccade Choices in Internally Guided Decisions.

    Science.gov (United States)

    Christopoulos, Vassilios N; Bonaiuto, James; Kagan, Igor; Andersen, Richard A

    2015-08-19

    The posterior parietal cortex (PPC) has traditionally been considered important for awareness, spatial perception, and attention. However, recent findings provide evidence that the PPC also encodes information important for making decisions. These findings have initiated a running argument of whether the PPC is critically involved in decision making. To examine this issue, we reversibly inactivated the parietal reach region (PRR), the area of the PPC that is specialized for reaching movements, while two monkeys performed a memory-guided reaching or saccade task. The task included choices between two equally rewarded targets presented simultaneously in opposite visual fields. Free-choice trials were interleaved with instructed trials, in which a single cue presented in the peripheral visual field defined the reach and saccade target unequivocally. We found that PRR inactivation led to a strong reduction of contralesional choices, but only for reaches. On the other hand, saccade choices were not affected by PRR inactivation. Importantly, reaching and saccade movements to single instructed targets remained largely intact. These results cannot be explained as an effector-nonspecific deficit in spatial attention or awareness, since the temporary "lesion" had an impact only on reach choices. Hence, the PPR is a part of a network for reach decisions and not just reach planning. There has been an ongoing debate on whether the posterior parietal cortex (PPC) represents only spatial awareness, perception, and attention or whether it is also involved in decision making for actions. In this study we explore whether the parietal reach region (PRR), the region of the PPC that is specialized for reaches, is involved in the decision process. We inactivated the PRR while two monkeys performed reach and saccade choices between two targets presented simultaneously in both hemifields. We found that inactivation affected only the reach choices, while leaving saccade choices intact

  18. Instrument for Study of Microbial Thermal Inactivation

    Science.gov (United States)

    Dickerson, R. W.; Read, R. B.

    1968-01-01

    An instrument was designed for the study of thermal inactivation of microorganisms using heating times of less than 1 sec. The instrument operates on the principle of rapid automatic displacement of the microorganism to and from a saturated steam atmosphere, and the operating temperature range is 50 to 90 C. At a temperature of 70 C, thermometric lag (time required to respond to 63.2% of a step change) of the fluid sample containing microorganisms was 0.12 sec. Heating time required to heat the sample to within 0.1 C of the exposure temperature was less than 1 sec, permitting exposure periods as brief as 1 sec, provided the proper corrections are made for the lethal effect of heating. The instrument is most useful for heat exposure periods of less than 5 min, and, typically, more than 500 samples can be processed for microbial inactivation determinations within an 8-hr period. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 7 Fig. 8 PMID:4874466

  19. Photodynamic inactivation of pathogens causing infectious keratitis

    Science.gov (United States)

    Simon, Carole; Wolf, G.; Walther, M.; Winkler, K.; Finke, M.; Hüttenberger, D.; Bischoff, Markus; Seitz, B.; Cullum, J.; Foth, H.-J.

    2014-03-01

    The increasing prevalence of antibiotic resistance requires new approaches also for the treatment of infectious keratitis. Photodynamic Inactivation (PDI) using the photosensitizer (PS) Chlorin e6 (Ce6) was investigated as an alternative to antibiotic treatment. An in-vitro cornea model was established using porcine eyes. The uptake of Ce6 by bacteria and the diffusion of the PS in the individual layers of corneal tissue were investigated by fluorescence. After removal of the cornea's epithelium Ce6-concentrations tested in liquid culture against different concentrations of Ce6 (1 - 512 μM) using 10 minutes irradiation (E = 18 J/cm2 ). This demonstrated that a complete inactivation of the pathogen strains were feasible whereby SA was slightly more susceptible than PA. 3909 mutants of the Keio collection of Escherichia coli (E.coli) were screened for potential resistance factors. The sensitive mutants can be grouped into three categories: transport mutants, mutants in lipopolysaccharide synthesis and mutants in the bacterial SOS-response. In conclusion PDI is seen as a promising therapy concept for infectious keratitis.

  20. Emotionally Intelligent Leadership: An Analysis of Targeted Interventions for Aspiring School Leaders in Texas

    Science.gov (United States)

    Kearney, W. Sean; Kelsey, Cheryl; Sinkfield, Carolin

    2014-01-01

    This study measures the impact of targeted interventions on the emotional intelligence of aspiring principals. The interventions utilized were designed by Nelson and Low (2011) to increase emotionally intelligent leadership skills in the following six areas: social awareness/active listening; anxiety management; decision making; appropriate use of…

  1. A general methodology for three-dimensional analysis of variation in target volume delineation

    NARCIS (Netherlands)

    Remeijer, P.; Rasch, C.; Lebesque, J. V.; van Herk, M.

    1999-01-01

    A generic method for three-dimensional (3-D) evaluation of target volume delineation in multiple imaging modalities is presented. The evaluation includes geometrical and statistical methods to estimate observer differences and variability in defining the Gross Tumor Volume (GTV) in relation to the

  2. psRNATarget: a plant small RNA target analysis server (2017 release).

    Science.gov (United States)

    Dai, Xinbin; Zhuang, Zhaohong; Zhao, Patrick Xuechun

    2018-04-30

    Plant regulatory small RNAs (sRNAs), which include most microRNAs (miRNAs) and a subset of small interfering RNAs (siRNAs), such as the phased siRNAs (phasiRNAs), play important roles in regulating gene expression. Although generated from genetically distinct biogenesis pathways, these regulatory sRNAs share the same mechanisms for post-translational gene silencing and translational inhibition. psRNATarget was developed to identify plant sRNA targets by (i) analyzing complementary matching between the sRNA sequence and target mRNA sequence using a predefined scoring schema and (ii) by evaluating target site accessibility. This update enhances its analytical performance by developing a new scoring schema that is capable of discovering miRNA-mRNA interactions at higher 'recall rates' without significantly increasing total prediction output. The scoring procedure is customizable for the users to search both canonical and non-canonical targets. This update also enables transmitting and analyzing 'big' data empowered by (a) the implementation of multi-threading chunked file uploading, which can be paused and resumed, using HTML5 APIs and (b) the allocation of significantly more computing nodes to its back-end Linux cluster. The updated psRNATarget server has clear, compelling and user-friendly interfaces that enhance user experiences and present data clearly and concisely. The psRNATarget is freely available at http://plantgrn.noble.org/psRNATarget/.

  3. In Vivo Phosphoproteomics Analysis Reveals the Cardiac Targets of β-Adrenergic Receptor Signaling

    DEFF Research Database (Denmark)

    Lundby, Alicia; Andersen, Martin N; Steffensen, Annette B

    2013-01-01

    β-Blockers are widely used to prevent cardiac arrhythmias and to treat hypertension by inhibiting β-adrenergic receptors (βARs) and thus decreasing contractility and heart rate. βARs initiate phosphorylation-dependent signaling cascades, but only a small number of the target proteins are known. We...

  4. Fluorescence analysis of the Hansenula polymorpha peroxisomal targeting signal-1 receptor, Pex5p

    NARCIS (Netherlands)

    Boteva, R.; Koek, A.; Visser, N.V.; Visser, A.J.W.G.; Krieger, E.; Zlateva, T.; Veenhuis, M.; Klei, van der I.

    2003-01-01

    Correct sorting of newly synthesized peroxisomal matrix proteins is dependent on a peroxisomal targeting signal (PTS). So far two PTSs are known. PTS1 consists of a tripeptide that is located at the extreme C terminus of matrix proteins and is specifically recognized by the PTS1-receptor Pex5p. We

  5. The Relationship between Retailers' Targeting and E-Commerce Strategies: An Empirical Analysis.

    Science.gov (United States)

    Doherty, Neil F.; Ellis-Chadwick, Fiona E.

    2003-01-01

    This survey of senior marketing executives in the United Kingdom's largest retail organizations investigated the extent to which the adoption of e-commerce is influenced by the socio-demographic characteristics of their target customers. Results demonstrate that organizations are most likely to adopt the Internet if their typical customer is male,…

  6. Translation Strategies from Target Culture Perspective: An Analysis of English and Chinese Brands Names

    Directory of Open Access Journals (Sweden)

    Hong Shi

    2017-03-01

    Full Text Available As a crucial communication material, the brand name exhibits its growing importance in the worldwide communication. It is a special text with a strong function and a clear persuasive purpose. This paper aims to explore the translation strategy and methods of English brand names from the perspective of culture. According to Skopostheorie, the prime principle determining any translation process is the purpose of the overall translational action. The translation methods should be based on the text’s function and the target culture. This paper is a tentative study of the guiding strategy and possible methods used in English brand names translation by analyzing the Chinese and English brand names, and how they fulfill the function of promoting products and enhancing the cultural exchange in the hope of offering a new perspective in the brand name translation practice. The study used the Skopostheorie as the guiding theory and strategy to analyze English brand names, which were selected from the brand names database “brandirectory”. It is found that the translation should follow the target-culture oriented strategy to conform to the habitual use of target language, social culture and aesthetics in target market.

  7. Effect of sulfasalazine on human neuroblastoma: Analysis of sepiapterin reductase (SPR) as a new therapeutic target

    NARCIS (Netherlands)

    L.P. Yco (Lisette P.); D. Geerts (Dirk); G. Mocz (Gabor); J. Koster (Jan); A.S. Bachmann (André)

    2015-01-01

    textabstractBackground: Neuroblastoma (NB) is an aggressive childhood malignancy in children up to 5 years of age. High-stage tumors frequently relapse even after aggressive multimodal treatment, and then show therapy resistance, typically resulting in patient death. New molecular-targeted compounds

  8. Effect of sulfasalazine on human neuroblastoma: analysis of sepiapterin reductase (SPR) as a new therapeutic target

    NARCIS (Netherlands)

    Yco, Lisette P.; Geerts, Dirk; Mocz, Gabor; Koster, Jan; Bachmann, André S.

    2015-01-01

    Neuroblastoma (NB) is an aggressive childhood malignancy in children up to 5 years of age. High-stage tumors frequently relapse even after aggressive multimodal treatment, and then show therapy resistance, typically resulting in patient death. New molecular-targeted compounds that effectively

  9. An efficient numerical target strength prediction model: Validation against analysis solutions

    NARCIS (Netherlands)

    Fillinger, L.; Nijhof, M.J.J.; Jong, C.A.F. de

    2014-01-01

    A decade ago, TNO developed RASP (Rapid Acoustic Signature Prediction), a numerical model for the prediction of the target strength of immersed underwater objects. The model is based on Kirchhoff diffraction theory. It is currently being improved to model refraction, angle dependent reflection and

  10. Workplace bullying as sensemaking: An analysis of target and actor perspectives on initial hostile interactions

    Czech Academy of Sciences Publication Activity Database

    Zábrodská, Kateřina; Ellwood, C.; Zaemdaar, S.; Mudrák, Jiří

    2016-01-01

    Roč. 22, č. 2 (2016), s. 136-157 ISSN 1475-9551 R&D Projects: GA ČR GPP407/10/P146; GA ČR GA14-02098S Institutional support: RVO:68081740 Keywords : workplace bullying * workplace hostility * sensemaking * target * actor * collective biography * stories Subject RIV: AN - Psychology Impact factor: 0.489, year: 2016

  11. Analysis and Modeling of Target Echo and Reverberation: FY15 Annual Report for ONR

    Science.gov (United States)

    2015-09-30

    particular interest is the target echo, which has not yet received a lot of attention , and for which good data were obtained during the TREX...essentially cut off all paths steeper than the critical angle. The coloured lines lines correspond to the differences between the group velocity formulation

  12. Inactivation of Mechanically Activated Piezo1 Ion Channels Is Determined by the C-Terminal Extracellular Domain and the Inner Pore Helix

    Directory of Open Access Journals (Sweden)

    Jason Wu

    2017-11-01

    Full Text Available Piezo proteins form mechanically activated ion channels that are responsible for our sense of light touch, proprioception, and vascular blood flow. Upon activation by mechanical stimuli, Piezo channels rapidly inactivate in a voltage-dependent manner through an unknown mechanism. Inactivation of Piezo channels is physiologically important, as it modulates overall mechanical sensitivity, gives rise to frequency filtering of repetitive mechanical stimuli, and is itself the target of numerous human disease-related channelopathies that are not well understood mechanistically. Here, we identify the globular C-terminal extracellular domain as a structure that is sufficient to confer the time course of inactivation and a single positively charged lysine residue at the adjacent inner pore helix as being required for its voltage dependence. Our results are consistent with a mechanism for inactivation that is mediated through voltage-dependent conformations of the inner pore helix and allosteric coupling with the C-terminal extracellular domain.

  13. Analysis of combinatorial regulation: scaling of partnerships between regulators with the number of governed targets.

    Directory of Open Access Journals (Sweden)

    Nitin Bhardwaj

    2010-05-01

    Full Text Available Through combinatorial regulation, regulators partner with each other to control common targets and this allows a small number of regulators to govern many targets. One interesting question is that given this combinatorial regulation, how does the number of regulators scale with the number of targets? Here, we address this question by building and analyzing co-regulation (co-transcription and co-phosphorylation networks that describe partnerships between regulators controlling common genes. We carry out analyses across five diverse species: Escherichia coli to human. These reveal many properties of partnership networks, such as the absence of a classical power-law degree distribution despite the existence of nodes with many partners. We also find that the number of co-regulatory partnerships follows an exponential saturation curve in relation to the number of targets. (For E. coli and Bacillus subtilis, only the beginning linear part of this curve is evident due to arrangement of genes into operons. To gain intuition into the saturation process, we relate the biological regulation to more commonplace social contexts where a small number of individuals can form an intricate web of connections on the internet. Indeed, we find that the size of partnership networks saturates even as the complexity of their output increases. We also present a variety of models to account for the saturation phenomenon. In particular, we develop a simple analytical model to show how new partnerships are acquired with an increasing number of target genes; with certain assumptions, it reproduces the observed saturation. Then, we build a more general simulation of network growth and find agreement with a wide range of real networks. Finally, we perform various down-sampling calculations on the observed data to illustrate the robustness of our conclusions.

  14. One pyrimidine dimer inactivates expression of a transfected gene in xeroderma pigmentosum cells

    International Nuclear Information System (INIS)

    Protic-Sabljic, M.; Kraemer, K.H.

    1985-01-01

    The authors have developed a host cell reactivation assay of DNA repair utilizing UV-treated plasmid vectors. The assay primarily reflects cellular repair of transcriptional activity of damaged DNA measured indirectly as enzyme activity of the transfected genes. They studied three plasmids (pSV2cat, 5020 base pairs; pSV2catSVgpt, 7268 base pairs; and pRSVcat, 5027 base pairs) with different sizes and promoters carrying the bacterial cat gene (CAT, chloramphenicol acetyltransferase) in a construction that permits cat expression in human cells. All human simian virus 40-transformed cells studied expressed high levels of the transfected cat gene. UV treatment of the plasmids prior to transfection resulted in differential decrease in CAT activity in different cell lines. With pSV2catSVgpt, UV inactivation of CAT expression was greater in the xeroderma pigmentosum group A and D lines than in the other human cell lines tested. The D 0 of the CAT inactivation curve was 50 J X m-2 for pSV2cat and for pRSVcat in the xeroderma pigmentosum group A cells. The similarity of the D0 data in the xeroderma pigmentosum group A cells for three plasmids of different size and promoters implies they all have similar UV-inactivation target size. UV-induced pyrimidine dimer formation in the plasmids was quantified by assay of the number of UV-induced T4 endonuclease V-sensitive sites. In the most sensitive xeroderma pigmentosum cells, with all three plasmids, one UV-induced pyrimidine dimer inactivates a target of about 2 kilobases, close to the size of the putative CAT mRNA

  15. Complicated biallelic inactivation of Pten in radiation-induced mouse thymic lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Yamaguchi, Yu [Department of Biology, Graduate School of Science, Chiba University, Yayoicho, Inage-ku, Chiba 263-8522 (Japan); Experimental Radiobiology for Children' s Health Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555 (Japan); Takabatake, Takashi; Kakinuma, Shizuko; Amasaki, Yoshiko; Nishimura, Mayumi; Imaoka, Tatsuhiko; Yamauchi, Kazumi; Shang, Yi [Experimental Radiobiology for Children' s Health Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555 (Japan); Miyoshi-Imamura, Tomoko [Experimental Radiobiology for Children' s Health Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555 (Japan); Genetic Counseling Program, Graduate School of Humanities and Sciences, Ochanomizu University, 2-1-1 Otsuka, Bunkyou-ku, Tokyo 112-8610 (Japan); Nogawa, Hiroyuki [Department of Biology, Graduate School of Science, Chiba University, Yayoicho, Inage-ku, Chiba 263-8522 (Japan); Kobayashi, Yoshiro [Department of Biomolecular Science, Faculty of Science, Toho University, Miyama 2-2-1, Funabashi, Chiba 274-8510 (Japan); Shimada, Yoshiya, E-mail: y_shimad@nirsgo.jp [Experimental Radiobiology for Children' s Health Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555 (Japan)

    2010-04-01

    Inactivation of the phosphatase and tensin homolog gene (Pten) occurs via multiple tissue-dependent mechanisms including epigenetic silencing, point mutations, insertions, and deletions. Although frequent loss of heterozygosity around the Pten locus and plausible involvement of epigenetic silencing have been reported in radiation-induced thymic lymphomas, the proportion of lymphomas with inactivated Pten and the spectrum of causal aberrations have not been extensively characterized. Here, we assessed the mode of Pten inactivation by comprehensive analysis of the expression and alteration of Pten in 23 radiation-induced thymic lymphomas developed in B6C3F1 mice. We found no evidence for methylation-associated silencing of Pten; rather, complex structural abnormalities comprised of missense and nonsense mutations, 1- and 3-bp insertions, and focal deletions were identified in 8 of 23 lymphomas (35%). Sequencing of deletion breakpoints suggested that aberrant V(D)J recombination and microhomology-mediated rearrangement were responsible for the focal deletions. Seven of the 8 lymphomas had biallelic alterations, and 4 of them did not express Pten protein. These Pten aberrations coincided with downstream Akt phosphorylation. In conclusion, we demonstrate that Pten inactivation is frequently biallelic and is caused by a variety of structural abnormalities (rather than by epigenetic silencing) and is involved in radiation-induced lymphomagenesis.

  16. Inactivation of bacterial biofilms using visible-light-activated unmodified ZnO nanorods

    Science.gov (United States)

    Aponiene, Kristina; Serevičius, Tomas; Luksiene, Zivile; Juršėnas, Saulius

    2017-09-01

    Various zinc oxide (ZnO) nanostructures are widely used for photocatalytic antibacterial applications. Since ZnO possesses a wide bandgap, it is believed that only UV light may efficiently assist bacterial inactivation, and diverse crystal lattice modifications should be applied in order to narrow the bandgap for efficient visible-light absorption. In this work we show that even unmodified ZnO nanorods grown by an aqueous chemical growth technique are found to possess intrinsic defects that can be activated by visible light (λ = 405 nm) and successfully applied for total inactivation of various highly resistant bacterial biofilms rather than more sensitive planktonic bacteria. Time-resolved fluorescence analysis has revealed that visible-light excitation creates long-lived charge carriers (τ > 1 μs), which might be crucial for destructive biochemical reactions achieving significant bacterial biofilm inactivation. ZnO nanorods covered with bacterial biofilms of Enterococcus faecalis MSCL 302 after illumination by visible light (λ = 405 nm) were inactivated by 2 log, and Listeria monocytogenes ATCL3C 7644 and Escherichia coli O157:H7 biofilms by 4 log. Heterogenic waste-water microbial biofilms, consisting of a mixed population of mesophilic bacteria after illumination with visible light were also completely destroyed.

  17. Normal X-inactivation mosaicism in corneas of heterozygous FlnaDilp2/+ female mice--a model of human Filamin A (FLNA diseases

    Directory of Open Access Journals (Sweden)

    Douvaras Panagiotis

    2012-02-01

    Full Text Available Abstract Background Some abnormalities of mouse corneal epithelial maintenance can be identified by the atypical mosaic patterns they produce in X-chromosome inactivation mosaics and chimeras. Human FLNA/+ females, heterozygous for X-linked, filamin A gene (FLNA mutations, display a range of disorders and X-inactivation mosaicism is sometimes quantitatively unbalanced. FlnaDilp2/+ mice, heterozygous for an X-linked filamin A (Flna nonsense mutation have variable eye, skeletal and other abnormalities, but X-inactivation mosaicism has not been investigated. The aim of this study was to determine whether X-inactivation mosaicism in the corneal epithelia of FlnaDilp2/+ mice was affected in any way that might predict abnormal corneal epithelial maintenance. Results X-chromosome inactivation mosaicism was studied in the corneal epithelium and a control tissue (liver of FlnaDilp2/+ and wild-type (WT female X-inactivation mosaics, hemizygous for the X-linked, LacZ reporter H253 transgene, using β-galactosidase histochemical staining. The corneal epithelia of FlnaDilp2/+ and WT X-inactivation mosaics showed similar radial, striped patterns, implying epithelial cell movement was not disrupted in FlnaDilp2/+ corneas. Corrected stripe numbers declined with age overall (but not significantly for either genotype individually, consistent with previous reports suggesting an age-related reduction in stem cell function. Corrected stripe numbers were not reduced in FlnaDilp2/+ compared with WT X-inactivation mosaics and mosaicism was not significantly more unbalanced in the corneal epithelia or livers of FlnaDilp2/+ than wild-type Flna+/+ X-inactivation mosaics. Conclusions Mosaic analysis identified no major effect of the mouse FlnaDilp2 mutation on corneal epithelial maintenance or the balance of X-inactivation mosaicism in the corneal epithelium or liver.

  18. The miRNAome of globe artichoke: conserved and novel micro RNAs and target analysis

    Directory of Open Access Journals (Sweden)

    De Paola Domenico

    2012-01-01

    Full Text Available Abstract Background Plant microRNAs (miRNAs are involved in post-transcriptional regulatory mechanisms of several processes, including the response to biotic and abiotic stress, often contributing to the adaptive response of the plant to adverse conditions. In addition to conserved miRNAs, found in a wide range of plant species a number of novel species-specific miRNAs, displaying lower levels of expression can be found. Due to low abundance, non conserved miRNAs are difficult to identify and isolate using conventional approaches. Conversely, deep-sequencing of small RNA (sRNA libraries can detect even poorly expressed miRNAs. No miRNAs from globe artichoke have been described to date. We analyzed the miRNAome from artichoke by deep sequencing four sRNA libraries obtained from NaCl stressed and control leaves and roots. Results Conserved and novel miRNAs were discovered using accepted criteria. The expression level of selected miRNAs was monitored by quantitative real-time PCR. Targets were predicted and validated for their cleavage site. A total of 122 artichoke miRNAs were identified, 98 (25 families of which were conserved with other plant species, and 24 were novel. Some miRNAs were differentially expressed according to tissue or condition, magnitude of variation after salt stress being more pronounced in roots. Target function was predicted by comparison to Arabidopsis proteins; the 43 targets (23 for novel miRNAs identified included transcription factors and other genes, most of which involved in the response to various stresses. An unusual cleaved transcript was detected for miR393 target, transport inhibitor response 1. Conclusions The miRNAome from artichoke, including novel miRNAs, was unveiled, providing useful information on the expression in different organs and conditions. New target genes were identified. We suggest that the generation of secondary short-interfering RNAs from miR393 target can be a general rule in the plant

  19. Monitoring Ground Deformation of Subway Area during the Construction Based on the Method of Multi-Temporal Coherent Targets Analysis

    Science.gov (United States)

    Zhang, L.; Wu, J.; Zhao, J.; Yuan, M.

    2018-04-01

    Multi-temporal coherent targets analysis is a high-precision and high-spatial-resolution monitoring method for urban surface deformation based on Differential Synthetic Aperture Radar (DInSAR), and has been successfully applied to measure land subsidence, landslide and strain accumulation caused by fault movement and so on. In this paper, the multi-temporal coherent targets analysis is used to study the settlement of subway area during the period of subway construction. The eastern extension of Shanghai Metro Line. 2 is taking as an example to study the subway settlement during the construction period. The eastern extension of Shanghai Metro Line. 2 starts from Longyang Road and ends at Pudong airport. Its length is 29.9 kilometers from east to west and it is a key transportation line to the Pudong Airport. 17 PalSAR images during 2007 and 2010 are applied to analyze and invert the settlement of the buildings nearby the subway based on the multi-temporal coherent targets analysis. But there are three significant deformation areas nearby the Line 2 between 2007 and 2010, with maximum subsidence rate up to 30 mm/y in LOS. The settlement near the Longyang Road station and Chuansha Town are both caused by newly construction and city expansion. The deformation of the coastal dikes suffer from heavy settlement and the rate is up to -30 mm/y. In general, the area close to the subway line is relatively stable during the construction period.

  20. Scale down of the inactivated polio vaccine production process

    NARCIS (Netherlands)

    Thomassen, Y.E.; Oever, van 't R.; Vinke, C.M.; Spiekstra, A.; Wijffels, R.H.; Pol, van der L.A.; Bakker, W.A.M.

    2013-01-01

    The anticipated increase in the demand for inactivated polio vaccines resulting from the success in the polio eradication program requires an increase in production capacity and cost price reduction of the current inactivated polio vaccine production processes. Improvement of existing production

  1. Thermal inactivation kinetics of β-galactosidase during bread baking

    NARCIS (Netherlands)

    Zhang, L.; Chen, Xiao Dong; Boom, R.M.; Schutyser, M.A.I.

    2017-01-01

    In this study, β-galactosidase was utilized as a model enzyme to investigate the mechanism of enzyme inactivation during bread baking. Thermal inactivation of β-galactosidase was investigated in a wheat flour/water system at varying temperature-moisture content combinations, and in bread during

  2. Quantum chromodynamics as the sequential fragmenting with inactivation

    International Nuclear Information System (INIS)

    Botet, R.

    1996-01-01

    We investigate the relation between the modified leading log approximation of the perturbative QCD and the sequential binary fragmentation process. We will show that in the absence of inactivation, this process is equivalent to the QCD gluodynamics. The inactivation term yields a precise prescription of how to include the hadronization in the QCD equations. (authors)

  3. Quantum chromodynamics as the sequential fragmenting with inactivation

    Energy Technology Data Exchange (ETDEWEB)

    Botet, R. [Paris-11 Univ., 91 - Orsay (France). Lab. de Physique des Solides; Ploszajczak, M. [Grand Accelerateur National d`Ions Lourds (GANIL), 14 - Caen (France)

    1996-12-31

    We investigate the relation between the modified leading log approximation of the perturbative QCD and the sequential binary fragmentation process. We will show that in the absence of inactivation, this process is equivalent to the QCD gluodynamics. The inactivation term yields a precise prescription of how to include the hadronization in the QCD equations. (authors). 15 refs.

  4. The pulsed light inactivation of veterinary relevant microbial biofilms ...

    African Journals Online (AJOL)

    Results show that both Cryptosporidium and Giardia attach to biofilms in large numbers (100-1000 oo/cysts) in as little as 72 hours. Pulsed light successfully inactivated all test species (Listeria, Salmonella, Bacillus, Escherichia) in planktonic and biofilm form with an increase in inactivation for every increase in UV dose.

  5. Ebola Virus Inactivation by Detergents Is Annulled in Serum

    NARCIS (Netherlands)

    van Kampen, Jeroen J. A.; Tintu, Andrei; Russcher, Henk; Fraaij, Pieter L. A.; Reusken, Chantal B. E. M.; Rijken, Mikel; van Hellemond, Jaap J.; van Genderen, Perry J. J.; Koelewijn, Rob; de Jong, Menno D.; Haddock, Elaine; Fischer, Robert J.; Munster, Vincent J.; Koopmans, Marion P. G.

    2017-01-01

    Treatment of blood samples from hemorrhagic fever virus (HFV)-infected patients with 0.1% detergents has been recommended for virus inactivation and subsequent safe laboratory testing. However, data on virus inactivation by this procedure are lacking. Here we show the effect of this procedure on

  6. Method of inactivating reproducible forms of mycoplasma in biological preparations

    International Nuclear Information System (INIS)

    Veber, P.; Jurmanova, K.; Lesko, J.; Hana, L.; Veber, V.

    1978-01-01

    Inactivation of mycoplasms in biological materials was achieved using gamma radiation with a dose rate of 1x10 4 to 5x10 6 rads/h for 1 to 250 hours. The technique is advantageous for allowing the inactivation of the final form of products (tablets, vaccines, etc.). (J.P.)

  7. Reliability analysis of minimum energy on target for laser facilities with more beam lines

    International Nuclear Information System (INIS)

    Chen Guangyu

    2008-01-01

    Shot reliability performance measures of laser facilities with more beam lines pertain to three categories: minimum-energy-on-target, power balance, and shot diagnostics. Accounting for symmetry of NIF beam line design and similarity of subset reliability in a same partition, a fault tree of meeting minimum-energy-on-target for the large laser facility shot of type K and a simplified method are presented, which are used to analyze hypothetic reliability of partition subsets in order to get trends of influences increasing number of beam lines and diverse shot types of large laser facilities on their shot reliability. Finally, it finds that improving component reliability is more crucial for laser facilities with more beam lines in comparison with those with beam lines and functional diversity from design flexibility is greatly helpful for improving shot reliability. (authors)

  8. Analysis of multiple-foil XRL targets using x-ray spectroscopy

    International Nuclear Information System (INIS)

    Wang, J.; Boehly, T.; Yaakobi, B.; Epstein, R.; Meyerhofer, D.; Richardson, M.C.; Russotto, M.; Soures, J.M.

    1989-01-01

    The multiple-foil collisional excitation x-ray laser targets proposed by LLE have been studied spectroscopically. Using spatially resolved 3d-2p x-ray spectra, the authors compare the temperatures and densities obtained in single- and double-foil geometries. They use the ratio of the dipole transitions to the electric quadrupole transitions in the Neon-like species as a density diagnostic. A non-LTE average-ion atomic physics model is used to describe the ionization process and a relativistic atomic physics code is used for calculation of the level energies, populations, and gain calculations. They support their claims that the double-vfoils provide higher densities and in some cases concave density profiles. The XUV spectra in the range of 20-300 A show the effect of target geometry and incident laser intensity on the lasing lines and the ionization balance

  9. Who uses apps in health promotion? A target group analysis of leaders.

    Science.gov (United States)

    Bregenzer, Anita; Wagner-Hartl, Verena; Jiménez, Paul

    2017-11-01

    User characteristics should be considered when designing features for e-health or m-health applications, as the developed solution should aim to support this specific target group. This study explores the effect of user characteristics (personality, health state, stress/recovery state, leadership behavior) on the interest and likelihood of using an app for health promotion activities at the workplace. Leaders are a key factor for the success of workplace health promotion; therefore, the target group of this study are leaders. The data of 412 leaders were collected in an online study. Hierarchical multiple linear regression analyses were conducted for four outcome criteria ("personal health," "contacting," "leadership feedback" and "corporate key figures"). The findings showed that neuroticism, physical health and health-promoting leadership were important predictors for using an app for monitoring personal health and getting in social contact about health issues. The stress/recovery state was significantly related to the feature of getting in social contact.

  10. Analysis of LFM-waveform Libraries for Cognitive Tracking Maneuvering Targets

    Directory of Open Access Journals (Sweden)

    Wang Hongyan

    2016-01-01

    Full Text Available Based on the idea of the waveform agility in cognitive radars,the waveform libraries for maneuvering target tracking are discussed. LFM-waveform libraries are designed according to different combinations of chirp parameters and FrFT rotation angles. By applying the interact multiple model (IMM algorithm in tracking maneuvering targets, transmitted waveform is called real time from the LFM-waveform libraries. The waveforms are selected from the library according to the criterion of maximum mutual information between the current state of knowledge of the model and the measurement. Simulation results show that waveform library containing certain amount LFM-waveforms can improve the performance of cognitive tracking radar.

  11. Analysis of penetration of steel and Al2O3 targets

    International Nuclear Information System (INIS)

    Littlefield, D.L.; Anderson, C.E. Jr.; Skaggs, S.R.

    1994-01-01

    A series of penetration experiments was conducted to investigate the ballistic performance of steel and 99.5% pure Al 2 O 3 targets using a L/D=10 tungsten alloy projectile. The impact velocity for the experiments was nominally 1.6 km/s. Flash radiographs were used to record the positions of the nose and tail of the projectile at discrete times. The experiments have been analyzed using an analytic penetration model. The steel data were matched quite well using reasonable values for the flow stress of the steel and tungsten alloy. Agreement with the ceramic data was not satisfactory, so the model was modified to account for constitutive behavior more relatistic in ceramic materials. Experimental data for the ceramic target were replicated reasonably well using the modified model when the slope of the yield strength/pressure curve was 0.75. copyright American Institute of Physics

  12. Use of Neoadjuvant Chemotherapy Plus Molecular Targeted Therapy in Colorectal Liver Metastases: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Sabanathan, Dhanusha; Eslick, Guy D; Shannon, Jenny

    2016-12-01

    Surgery remains the standard of care for patients with colorectal liver metastases (CLMs), with a 5-year survival rate approaching 35%. Perioperative chemotherapy confers a survival benefit in selected patients with CLMs. The use of molecular targeted therapy combined with neoadjuvant chemotherapy for CLMs, however, remains controversial. We reviewed the published data on combination neoadjuvant chemotherapy and molecular targeted therapy for resectable and initially unresectable CLMs. A literature search of the Medline and PubMed databases was conducted to identify studies of neoadjuvant chemotherapy plus molecular targeted therapy in the management of resectable or initially unresectable CLMs. We calculated the pooled proportion and 95% confidence intervals using a random effects model for the relationship of the combination neoadjuvant treatment on the overall response rate and performed a systematic review of all identified studies. The analysis was stratified according to the study design. The data from 11 studies of 908 patients who had undergone systemic chemotherapy plus targeted therapy for CLM were analyzed. The use of combination neoadjuvant therapy was associated with an overall response rate of 68% (95% confidence interval, 63%-73%), with significant heterogeneity observed in the studies (I 2  = 89.35; P chemotherapy plus molecular targeted agents for CLM confers high overall response rates. Combination treatment might also increase the resectability rates in initially unresectable CLM. Further studies are needed to examine the survival outcomes, with a focus on the differential role of molecular targeted therapy in the neoadjuvant versus adjuvant setting. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  13. Pre-Test Analysis of the MEGAPIE Spallation Source Target Cooling Loop Using the TRAC/AAA Code

    International Nuclear Information System (INIS)

    Bubelis, Evaldas; Coddington, Paul; Leung, Waihung

    2006-01-01

    A pilot project is being undertaken at the Paul Scherrer Institute in Switzerland to test the feasibility of installing a Lead-Bismuth Eutectic (LBE) spallation target in the SINQ facility. Efforts are coordinated under the MEGAPIE project, the main objectives of which are to design, build, operate and decommission a 1 MW spallation neutron source. The technology and experience of building and operating a high power spallation target are of general interest in the design of an Accelerator Driven System (ADS) and in this context MEGAPIE is one of the key experiments. The target cooling is one of the important aspects of the target system design that needs to be studied in detail. Calculations were performed previously using the RELAP5/Mod 3.2.2 and ATHLET codes, but in order to verify the previous code results and to provide another capability to model LBE systems, a similar study of the MEGAPIE target cooling system has been conducted with the TRAC/AAA code. In this paper a comparison is presented for the steady-state results obtained using the above codes. Analysis of transients, such as unregulated cooling of the target, loss of heat sink, the main electro-magnetic pump trip of the LBE loop and unprotected proton beam trip, were studied with TRAC/AAA and compared to those obtained earlier using RELAP5/Mod 3.2.2. This work extends the existing validation data-base of TRAC/AAA to heavy liquid metal systems and comprises the first part of the TRAC/AAA code validation study for LBE systems based on data from the MEGAPIE test facility and corresponding inter-code comparisons. (authors)

  14. Trading in Target Stocks Before Takeover Announcements: An Analysis of Stock and Option Markets

    OpenAIRE

    Marcus Clements; Harminder Singh; Antonie Van Eekelen

    2007-01-01

    In this study we examine both informed trading and contraire trading preceding takeover announcements on US target firms. Our findings suggest that both informed trading and contraire trading exists within the period preceding takeover announcements on both the stock and option markets as evident through abnormal returns and trading volumes. In regard to contraire trading, this study investigates possible explanations for its existence including liquidity clustering, falsely informed trading ...

  15. Empty pledges: A content analysis comparing Belgian and Dutch child-targeting food websites

    OpenAIRE

    Neyens, Evy; Smits, Tim

    2015-01-01

    Background: In the EU Pledge, the food industry has vowed to retain from unhealthy food promotion to children under the age of twelve. Nonetheless, food brands increasingly lure children to branded websites packed with unhealthy food and beverage advertising. This study first explores the prevalence of online marketing strategies on 49 Belgian and Dutch child-targeting food websites. Second, it examines the nutrient content of the advertised foods. Third, it scrutinizes whether Belgian and Du...

  16. Analysis of miRNAs targeting transcription factors in Persicaria minor induced by Fusarium oxysporum

    Science.gov (United States)

    Samad, Abdul Fatah A.; Ali, Nazaruddin Muhammad; Ismail, Ismanizan; Murad, Abdul Munir Abdul

    2016-11-01

    A recent discovery showed small non-coding RNA known as microRNA has a crucial role in plant development and plant survival in extreme condition. In the past few years, researchers have managed to identify the various families of transcription factors that play a crucial role in regulating plant development and plant responses to stresses. This study focuses on the expression pattern of miRNA targeted transcription factor under biotic stress in a plant rich with secondary metabolite, Persicaria minor. A pathogenic fungus, Fusarium oxysporum was used in the biotic stress treatment since the previous study revealed this fungus could trigger plant defense system. Two small RNA libraries were constructed which consist of control and treated samples. In order to identify the potential target, psRobot target prediction software was used for each miRNA that shows significant change due to the infection. The result showed miR156b/c, miR172a, miR319, miR858, and miR894 were found to be targeting a wide range of transcription factors that involve in plant development and plant response towards stresses. The expression of miR156b/c and miR172 were up-regulated while the expression of miR319, miR858, and miR894 was found to be down-regulated. These results may provide a certain level of networking between those two regulatory molecules in plant genetic system under biotic stress.

  17. NMR signal analysis in the large COMPASS $^{14}$NH$_{3}$ target

    CERN Document Server

    Koivuniemi, J; Hess, C; Kisselev, Y U; Meyer, W; Radtke, E; Reicherz, G; Doshita, N; Iwata, T; Kondo, K; Michigami, T

    2009-01-01

    In the large COMPASS polarized proton target the 1508 cm$^{3}$ of irradiated granular ammonia is polarized with dynamic nuclear polarization method using 4 mm microwaves in 2.5 T eld. The nuclear polarization up to 90 - 93 % is determined with cw NMR. The properties of the observed ammonia proton signals are described and spin thermodynamics in high elds is presented. Also the second moment of the NMR line is estimated.

  18. Targeted analysis with benchtop quadrupole–orbitrap hybrid mass spectrometer: Application to determination of synthetic hormones in animal urine

    International Nuclear Information System (INIS)

    Kumar, Praveen; Rúbies, Antoni; Centrich, Francesc; Granados, Mercè; Cortés-Francisco, Nuria; Caixach, Josep; Companyó, Ramon

    2013-01-01

    Graphical abstract: -- Highlights: •The quadrupole in Q Exactive acts as a powerful filter to reduce ion suppression. •Reducing mass range using quadrupole in targeted modes increases the S/N ratio. •Targeted SIM data dependent scan modes are the most suitable for residue analysis. •A HRMS confirmatory method for synthetic hormones in urine has been developed. •The Q Exactive provides similar sensitivity and enhanced selectivity compared to QqQ. -- Abstract: Sensitive and unequivocal determination of analytes/contaminants in complex matrices is a challenge in the field of food safety control. In this study, various acquisition modes (Full MS/AIF, Full MS + tMS/MS, Full MS/dd MS/MS and tSIM/ddMS/MS) and parameters of a quadrupole–orbitrap hybrid mass spectrometer (Q Exactive) were studied in detail. One of the main conclusions has been that, reducing the scan range for Full MS (using the quadrupole) and targeted modes give higher signal-to-noise (S/N) ratios and thereby better detection limits for analytes in matrix. The use of Q Exactive in a complex case, for the confirmatory analysis of hormones in animal urine is presented. A targeted SIM data dependent MS/MS (tSIM/ddMS/MS) acquisition method for determination of eight synthetic hormones (trenbolone, 17α ethinylestradiol, zeranol, stanozolol, dienestrol, diethylstilbestrol, hexestrol, taleranol) and a naturally occurring hormone (zearalenone) in animal urine were optimized to have sensitive precursors from targeted SIM mode and trigger MS/MS scans over the entire chromatograph peak. The method was validated according to EC/657/2002. CCα (decision limit) for the analytes ranged between 0.11 μg L −1 and 0.69 μg L −1 and CCβ (detection capability) ranged between 0.29 μg L −1 and 0.90 μg L −1

  19. Empirical Analysis of the Impact of Inflation Targeting on the Risk Premium

    Directory of Open Access Journals (Sweden)

    Krušković Borivoje D.

    2014-09-01

    Full Text Available The basis for the conduct of monetary policy is monetary policy strategy. Monetary strategy is necessary for monetary policy makers to analyse all relevant information in order to undertake effective policy actions. Inflation targeting has enabled countries to achieve low inflation in the very short term. Due to this, the financial markets have adjusted their long-term inflation expectations and incorporated them into the interest rate. Risk premiums that compensate for the uncertainty of inflation have fallen. The aim of this paper is to examine how the adoption of inflation targeting affects the movement of the risk premium. The hypothesis we want to test is that the adoption of inflation targeting affects the reduction of the country risk premium by affecting the formation of a more stable macroeconomic environment through a more stable and predictable inflation rate in the medium and long term. The method used for evaluating the regression coefficients is the dynamic panel generalized method of moments (GMM. This method involves the use of conditional moments in endogenous and exogenous variables with a lag as instruments for the assessment of differential equations, while the difference lagged endogenous variables are used as instruments in the levels equation.

  20. Integrated analysis of ischemic stroke datasets revealed sex and age difference in anti-stroke targets

    Directory of Open Access Journals (Sweden)

    Wen-Xing Li

    2016-09-01

    Full Text Available Ischemic stroke is a common neurological disorder and the burden in the world is growing. This study aims to explore the effect of sex and age difference on ischemic stroke using integrated microarray datasets. The results showed a dramatic difference in whole gene expression profiles and influenced pathways between males and females, and also in the old and young individuals. Furthermore, compared with old males, old female patients showed more serious biological function damage. However, females showed less affected pathways than males in young subjects. Functional interaction networks showed these differential expression genes were mostly related to immune and inflammation-related functions. In addition, we found ARG1 and MMP9 were up-regulated in total and all subgroups. Importantly, IL1A, ILAB, IL6 and TNF and other anti-stroke target genes were up-regulated in males. However, these anti-stroke target genes showed low expression in females. This study found huge sex and age differences in ischemic stroke especially the opposite expression of anti-stroke target genes. Future studies are needed to uncover these pathological mechanisms, and to take appropriate pre-prevention, treatment and rehabilitation measures.

  1. The target theory applied to the analysis of irradiation damages in organic detectors

    International Nuclear Information System (INIS)

    Mesquita, Carlos Henrique de

    2005-01-01

    The Target Theory was used to explain the radiation damage in samples containing 1% (g//L) of 2,5-diphenyl-oxazolyl (PPO) diluted in toluene and irradiated with 60 Co (1.8 Gy/s). The survival molecules of irradiated PPO obeys the bi-exponential mathematical model [74.3 x exp(-D/104.3) + 25.7 x exp(-D/800,0)]. It indicates that 74.3% of the molecules decay with D37=104.3 kGy and 25.7% decay with D37=800 kGy. From the Target Theory it was inferred the energies involved in the irradiation damages which were 0.239 ± 0.031 eV (G=418.4 ± 54.1. damages/100 eV) and 1.83 ± 0.30 eV (54.5 ± 8.9 damages/100 eV). The diameter of PPO molecule estimated from the Target Theory is in the interval of 45.5 to 64.9 angstrom. (author)

  2. Chlorophyll mediated photodynamic inactivation of blue laser on Streptococcus mutans

    Science.gov (United States)

    Astuti, Suryani Dyah; Zaidan, A.; Setiawati, Ernie Maduratna; Suhariningsih

    2016-03-01

    Photodynamic inactivation is an inactivation method in microbial pathogens that utilize light and photosensitizer. This study was conducted to investigate photodynamic inactivation effects of low intensity laser exposure with various dose energy on Streptococcus mutans bacteria. The photodynamic inactivation was achieved with the addition of chlorophyll as photosensitizers. To determine the survival percentage of Streptococcus mutans bacteria after laser exposure, the total plate count method was used. For this study, the wavelength of the laser is 405 nm and variables of energy doses are 1.44, 2.87, 4.31, 5.74, 7.18, and 8.61 in J/cm2. The results show that exposure to laser with energy dose of 7.18 J/cm2 has the best photodynamic inactivation with a decrease of 78% in Streptococcus

  3. Modelling and application of the inactivation of microorganism

    International Nuclear Information System (INIS)

    Oğuzhan, P.; Yangılar, F.

    2013-01-01

    Prevention of consuming contaminated food with toxic microorganisms causing infections and consideration of food protection and new microbial inactivation methods are obligatory situations. Food microbiology is mainly related with unwanted microorganisms spoiling foods during processing and transporting stages and causing diseases. Determination of pathogen microorganisms is important for human health to define and prevent dangers and elongate shelf life. Inactivation of pathogen microorganisms can provide food security and reduce nutrient losses. Microbial inactivation which is using methods of food protection such as food safety and fresh. With this aim, various methods are used such as classical thermal processes (pasteurisation, sterilisation), pressured electrical field (PEF), ionised radiation, high pressure, ultrasonic waves and plasma sterilisation. Microbial inactivation modelling is a secure and effective method in food production. A new microbiological application can give useful results for risk assessment in food, inactivation of microorganisms and improvement of shelf life. Application and control methods should be developed and supported by scientific research and industrial applications

  4. Open source tracking and analysis of adult Drosophila locomotion in Buridan's paradigm with and without visual targets.

    Directory of Open Access Journals (Sweden)

    Julien Colomb

    Full Text Available BACKGROUND: Insects have been among the most widely used model systems for studying the control of locomotion by nervous systems. In Drosophila, we implemented a simple test for locomotion: in Buridan's paradigm, flies walk back and forth between two inaccessible visual targets [1]. Until today, the lack of easily accessible tools for tracking the fly position and analyzing its trajectory has probably contributed to the slow acceptance of Buridan's paradigm. METHODOLOGY/PRINCIPAL FINDINGS: We present here a package of open source software designed to track a single animal walking in a homogenous environment (Buritrack and to analyze its trajectory. The Centroid Trajectory Analysis (CeTrAn software is coded in the open source statistics project R. It extracts eleven metrics and includes correlation analyses and a Principal Components Analysis (PCA. It was designed to be easily customized to personal requirements. In combination with inexpensive hardware, these tools can readily be used for teaching and research purposes. We demonstrate the capabilities of our package by measuring the locomotor behavior of adult Drosophila melanogaster (whose wings were clipped, either in the presence or in the absence of visual targets, and comparing the latter to different computer-generated data. The analysis of the trajectories confirms that flies are centrophobic and shows that inaccessible visual targets can alter the orientation of the flies without changing their overall patterns of activity. CONCLUSIONS/SIGNIFICANCE: Using computer generated data, the analysis software was tested, and chance values for some metrics (as well as chance value for their correlation were set. Our results prompt the hypothesis that fixation behavior is observed only if negative phototaxis can overcome the propensity of the flies to avoid the center of the platform. Together with our companion paper, we provide new tools to promote Open Science as well as the collection and

  5. Results and analysis of high heat flux tests on a full scale vertical target prototype of ITER divertor

    International Nuclear Information System (INIS)

    Missirlian, M.; Escourbiac, F.; Schlosser, J.; Durocher, A.; Bobin-Vastra, I.

    2004-01-01

    After an extensive development program, a Full-Scale Divertor Target prototype (VTFS) manufactured with all the main features of the corresponding ITER divertor, was intensively tested in the high heat flux FE200 facility. The prototype consists of four units having a full mono-block geometry. The lower part (CFC armour) and the upper part (W armour) of each mono-block were joined to the solution annealed, quenched and cold worked CuCrZr tube by HIP technique. The CFC mono-block was successfully tested up to 1000 cycles at 23 MW/m 2 without any indication of failure. This value is well beyond the ITER design target of 300 cycles at 20 MW/m 2 . The W mono-block endured ∼600 cycles at 10 MW/m 2 . This value of flux is one order of magnitude higher than the ITER design target for the upper part of the vertical target. Fatigue damage is observed when pursuing the cycling up to 15 MW/m 2 . A first stress analysis seems to predict these factual results. However, macro-graphic examinations should bring a better damage valuation. Meanwhile, the fatigue testing will continue on the W healthy part of the VTFS prototype with castellation located on the heated surface (reducing the stresses close to the W-Cu interface). (authors)

  6. Results and analysis of high heat flux tests on a full scale vertical target prototype of ITER divertor

    Energy Technology Data Exchange (ETDEWEB)

    Missirlian, M.; Escourbiac, F.; Schlosser, J.; Durocher, A. [Association Euratom-CEA, Centre d' Etudes de Cadarache, 13 - Saint-Paul-lez-Durance (France). Dept. de Recherches sur la Fusion Controlee; Merola, M. [EFDA Close Support Unit, Garching (Germany); Bobin-Vastra, I. [Framatome, 71 - Le Creusot (France)

    2004-07-01

    After an extensive development program, a Full-Scale Divertor Target prototype (VTFS) manufactured with all the main features of the corresponding ITER divertor, was intensively tested in the high heat flux FE200 facility. The prototype consists of four units having a full mono-block geometry. The lower part (CFC armour) and the upper part (W armour) of each mono-block were joined to the solution annealed, quenched and cold worked CuCrZr tube by HIP technique. The CFC mono-block was successfully tested up to 1000 cycles at 23 MW/m{sup 2} without any indication of failure. This value is well beyond the ITER design target of 300 cycles at 20 MW/m{sup 2}. The W mono-block endured {approx}600 cycles at 10 MW/m{sup 2}. This value of flux is one order of magnitude higher than the ITER design target for the upper part of the vertical target. Fatigue damage is observed when pursuing the cycling up to 15 MW/m{sup 2}. A first stress analysis seems to predict these factual results. However, macro-graphic examinations should bring a better damage valuation. Meanwhile, the fatigue testing will continue on the W healthy part of the VTFS prototype with castellation located on the heated surface (reducing the stresses close to the W-Cu interface). (authors)

  7. An Analysis of Determinants of Under-5 Mortality across Countries: Defining Priorities to Achieve Targets in Sustainable Developmental Goals.

    Science.gov (United States)

    Acheampong, Michael; Ejiofor, Chukwudi; Salinas-Miranda, Abraham

    2017-06-01

    Objectives The end of the era of millennium development goals (MDGs) ushered in the sustainable development goals (SDGs) with a new target for the reduction of under-five mortality rates (U5MR). Although U5MR decreased globally, the reduction was insufficient to meet MDGs targets because significant socioeconomic inequities remain unaddressed across and within countries. Thus, further progress in achieving the new SDGs target will be hindered if there is no adequate prioritization of important socioeconomic, healthcare, and environmental factors. The objective of this study was to assess factors that account most for the differences in U5MR between countries around the globe. Methods We conducted an ordinary least squares (OLS) regression-based prioritization analysis of socioeconomic, healthcare, and environmental variables from 109 countries to understand which factors explain the differences in U5MR best. Results All indicators examined individually affected differences in U5MR between countries. However, the results of multivariate OLS regression showed that the most important factors that accounted for the differences were, in order: fertility rate, total health expenditure per capita, access to improved water and sanitation, and female employment rate. Conclusions To achieve the new global target for U5MR, policymakers must focus on certain priority areas, such as interventions that address access to affordable maternal healthcare services, educational programs for mothers, especially those who are adolescents, and safe drinking water and sanitation.

  8. Inactivation of Coxiella burnetti by gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Scott, G.H.; McCaul, T.F.; Williams, J.C.

    1989-01-01

    The gamma radiation inactivation kinetics for Coxiella burnetii at - 79 C were exponential. The radiation dose needed to reduce the number of infective C. burnetii by 90% varied from 0-64 to 1.2 kGy depending on the phase of hte micro-organism, purity of the culture and composition of suspending menstruum. The viability of preparations containing C. burnetti was completely abolished by 10 kGy without diminishing antigenicity or ability to elicit a protective immune response in vaccinated mice. Immunocytochemical examinations using monoclonal antibodies and electron microscopy demonstrated that radiation doses of 20 kGy did not alter cell-wall morphology or cell-surface antigenic epitopes.

  9. Inactivation of Coxiella burnetii by gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Scott, G.H.; McCaul, T.F. (Army Medical Research Inst. of Infectious Diseases, Fort Detrick, Frederick, MD (USA)); Williams, J.C. (National Inst. of Allergy and Infectious Diseases, Bethesda, MD (USA))

    1989-12-01

    The gamma radiation inactivation kinetics for Coxiella burnetii at - 79{sup 0}C were exponential. The radiation dose needed to reduce the number of infective C. burnetii by 90% varied from 0.64 to 1.2 kGy depending on the phase of the micro-organism, purity of the culture and composition of suspending menstruum. The viability of preparations containing 10{sup 11} C. burnetii ml{sup -1} was completely abolished by 10 kGy without diminishing antigenicity or ability to elicit a protective immune response in vaccinated mice. Immunocytochemical examinations using monoclonal antibodies and electron microscopy demonstrated that radiation doses of 20 kGy did not alter cell-wall morphology or cell-surface antigenic epitopes. (author).

  10. Inactivation of mitochondrial ATPase by ultraviolet light

    International Nuclear Information System (INIS)

    Chavez, E.; Cuellar, A.

    1984-01-01

    The present work describes experiments that show that far-ultraviolet irradiation induce the inhibition of ATPase activity in both membrane-bound and soluble F1. It was also found that ultraviolet light promotes the release of tightly bound adenine nucleotides from F1-ATPase. Experiments carried out with submitochondrial particles indicate that succinate partially protects against these effects of ultraviolet light. Titration of sulfhydryl groups in both irradiated submitochondrial particles and soluble F1-ATPase indicates that a conformational change induced by photochemical modifications of amino acid residues appears involved in the inactivation of the enzyme. Finally, experiments are described which show that the tyrosine residue located in the active site of F1-ATPase is modified by ultraviolet irradiation

  11. Inactivation of Coxiella burnetii by gamma irradiation

    International Nuclear Information System (INIS)

    Scott, G.H.; McCaul, T.F.; Williams, J.C.

    1989-01-01

    The gamma radiation inactivation kinetics for Coxiella burnetii at - 79 0 C were exponential. The radiation dose needed to reduce the number of infective C. burnetii by 90% varied from 0.64 to 1.2 kGy depending on the phase of the micro-organism, purity of the culture and composition of suspending menstruum. The viability of preparations containing 10 11 C. burnetii ml -1 was completely abolished by 10 kGy without diminishing antigenicity or ability to elicit a protective immune response in vaccinated mice. Immunocytochemical examinations using monoclonal antibodies and electron microscopy demonstrated that radiation doses of 20 kGy did not alter cell-wall morphology or cell-surface antigenic epitopes. (author)

  12. Esterase resistant to inactivation by heavy metals

    KAUST Repository

    El, Dorry Hamza

    2014-09-25

    EstATII is an esterase that a halotolerant, thermophilic and resistant to a spectrum of heavy metals including toxic concentration of metals. It was isolated from the lowest convective layer of the Atlantis II Red Sea brine pool. The Atlantis II brine pool is an extreme environment that possesses multiple harsh conditions such as; high temperature, salinity, pH and high concentration of metals, including toxic heavy metals. A fosmid metagenomic library using DNA isolated from the lowest convective layer this pool was used to identify EstATII. Polynucleotides encoding EstATII and similar esterases are disclosed and can be used to make EstATII. EstATII or compositions or apparatuses that contain it may be used in various processes employing lipases/esterases especially when these processes are performed under harsh conditions that inactivate other kinds of lipases or esterases.

  13. Polyphenol Oxidase Enzyme and Inactivation Methods

    Directory of Open Access Journals (Sweden)

    Leman Yılmaz

    2018-03-01

    Full Text Available Polyphenol oxidase enzyme is found in vegetables and fruits, as well as in some animal organs and microorganisms. Polyphenol oxidase enzyme responsible for enzymatic browning is a group of copper proteins that catalyses the oxidation of phenolic compounds to quinones, which produce brown pigments, commonly found in fruits and vegetables. During the industrial preparation of fruits and vegetables, results of catalytic effect of polyphenol oxidase causes enzymatic browning. Enzymatic browning impairs the appearance of products containing phenolic compounds along with undesirable colour, odor and taste formation and significant loss of nutritional value of the products. This affects the acceptability of the products by the consumers and causes economic losses. In this review, some characteristics of polyphenol oxidase enzyme in different fruits and vegetables have been reviewed and information about chemical antibrowning agents, thermal applications, irradiation applications and alternative methods such as high pressure processing, pulse electric field, supercritical carbon dioxide and ultrasound applications to inactivate this enzyme has been presented.

  14. UV inactivation of pathogenic and indicator microorganisms

    International Nuclear Information System (INIS)

    Chang, J.C.; Ossoff, S.F.; Lobe, D.C.; Dorfman, M.H.; Dumais, C.M.; Qualls, R.G.; Johnson, J.D.

    1985-01-01

    Survival was measured as a function of the dose of germicidal UV light for the bacteria Escherichia coli, Salmonella typhi, Shigella sonnei, Streptococcus faecalis, Staphylococcus aureus, and Bacillus subtilis spores, the enteric viruses poliovirus type 1 and simian rotavirus SA11, the cysts of the protozoan Acanthamoeba castellanii, as well as for total coliforms and standard plate count microorganisms from secondary effluent. The doses of UV light necessary for a 99.9% inactivation of the cultured vegetative bacteria, total coliforms, and standard plate count microorganisms were comparable. However, the viruses, the bacterial spores, and the amoebic cysts required about 3 to 4 times, 9 times, and 15 times, respectively, the dose required for E. coli. These ratios covered a narrower relative dose range than that previously reported for chlorine disinfection of E. coli, viruses, spores, and cysts

  15. UV inactivation of pathogenic and indicator microorganisms

    Energy Technology Data Exchange (ETDEWEB)

    Chang, J.C.; Ossoff, S.F.; Lobe, D.C.; Dorfman, M.H.; Dumais, C.M.; Qualls, R.G.; Johnson, J.D.

    1985-06-01

    Survival was measured as a function of the dose of germicidal UV light for the bacteria Escherichia coli, Salmonella typhi, Shigella sonnei, Streptococcus faecalis, Staphylococcus aureus, and Bacillus subtilis spores, the enteric viruses poliovirus type 1 and simian rotavirus SA11, the cysts of the protozoan Acanthamoeba castellanii, as well as for total coliforms and standard plate count microorganisms from secondary effluent. The doses of UV light necessary for a 99.9% inactivation of the cultured vegetative bacteria, total coliforms, and standard plate count microorganisms were comparable. However, the viruses, the bacterial spores, and the amoebic cysts required about 3 to 4 times, 9 times, and 15 times, respectively, the dose required for E. co