21 results on '"Ward, DP"'
Search Results
2. Review of particle physics
- Author
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Hagiwara, K, Hikasa, K, Nakamura, K, Tanabashi, M, Aguilar-Benitez, M, Amsler, C, Barnett, RM, Burchat, PR, Carone, CD, Caso, C, Conforto, G, Dahl, O, Doser, M, Eidelman, S, Feng, JL, Gibbons, L, Goodman, M, Grab, C, Groom, DE, Gurtu, A, Hayes, KG, Hernandez-Rey, JJ, Honscheid, K, Kolda, C, Mangano, ML, Manley, DM, Manohar, AV, March-Russell, J, Masoni, A, Miquel, R, Monig, K, Murayama, H, Navas, S, Olive, KA, Pape, L, Patrignani, C, Piepke, A, Roos, M, Terning, J, Tornqvist, NA, Trippe, TG, Vogel, P, Wohl, CG, Workman, RL, Yao, WM, Armstrong, B, Gee, PS, Lugovsky, KS, Lugovsky, SB, Lugovsky, VS, Artuso, M, Asner, D, Babu, KS, Barberio, E, Battaglia, M, Bichsel, H, Biebel, O, Bloch, P, Cahn, RN, Cattai, A, Chivukula, RS, Cousins, RD, Cowan, G, Damour, T, Desler, K, Donahue, RJ, Edwards, DA, Elvira, VD, Erler, J, Ezhela, VV, Fasso, A, Fetscher, W, Fields, BD, Foster, B, Froidevaux, D, Fukugita, M, Gaisser, TK, Garren, L, Gerber, HJ, Gilman, FJ, Haber, HE, Hagmann, C, Hewett, J, Hinchliffe, I, Hogan, CJ, Hohler, G, Igo-Kemenes, P, Jackson, JD, Johnson, KF, Karlen, D, Kayser, B, Klein, SR, Kleinknecht, K, Knowles, IG, Kreitz, P, Kuyanov, YV, Landua, R, Langacker, P, Littenberg, L, Martin, AD, Nakada, T, Narain, M, Nason, P, Peacock, JA, Quinn, HR, Raby, S, Raffelt, G, Razuvaev, EA, Renk, B, Rolandi, L, Ronan, MT, Rosenberg, LJ, Sachrajda, CT, Sanda, AI, Sarkar, S, Schmitt, M, Schneider, O, Scott, D, Seligman, WG, Shaevitz, MH, Sjostrand, T, Smoot, GF, Spanier, S, Spieler, H, Spooner, NJC, Srednicki, M, Stahl, A, Stanev, T, Suzuki, M, Tkachenko, NP, Valencia, G, van Bibber, K, Vincter, MG, Ward, DP, Webber, BR, Whalley, M, Wolfenstein, L, Womersley, J, Woody, CL, Zenin, OV, and Grp, PD
- Subjects
High Energy Physics::Phenomenology ,High Energy Physics::Experiment - Abstract
This biennial Review summarizes much of Particle Physics. Using data from previous editions, plus 2205 new measurements from 667 papers, we list, evaluate, and average measured properties of gauge bosons, leptons, quarks, mesons, and baryons. We also summarize searches for hypothetical particles such as Higgs bosons, heavy neutrinos, and supersymmetric particles. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as the Standard Model, particle detectors, probability, and statistics. This edition features expanded coverage of CP violation in B mesons and of neutrino oscillations. For the first time we cover searches for evidence of extra dimensions (both in the particle listings and in a new review). Another new review is on Grand Unified Theories. A booklet is available containing the Summary Tables and abbreviated versions of some of the other sections of this full Review. All tables, listings, and reviews (and errata) are also available on the Particle Data Group website: http://pdg.lbl.gov.
- Published
- 2002
3. Der Verschluss der Nasenhaupthöhle modifiziert nach Young zur Behandlung der Epistaxis bei der hereditären hämorrhagischen Teleangiektasie - eine multizentrische Auswertung
- Author
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Geisthoff, U, Richer, SL, Livada, N, Ward, DP, Johnson, L, Mainka, A, White Jr., RI, Maune, S, Ross, DA, Geisthoff, U, Richer, SL, Livada, N, Ward, DP, Johnson, L, Mainka, A, White Jr., RI, Maune, S, and Ross, DA
- Published
- 2012
4. Evaluating the risk of data loss due to particle radiation damage in a DNA data storage system.
- Author
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Takahashi CN, Ward DP, Cazzaniga C, Frost C, Rech P, Ganguly K, Blanchard S, Wender S, Nguyen BH, and Smith JA
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- Neutrons adverse effects, DNA Damage radiation effects, Information Storage and Retrieval methods, Radiation, Ionizing, Kinetics, DNA radiation effects
- Abstract
DNA data storage is a potential alternative to magnetic tape for archival storage purposes, promising substantial gains in information density. Critical to the success of DNA as a storage media is an understanding of the role of environmental factors on the longevity of the stored information. In this paper, we evaluate the effect of exposure to ionizing particle radiation, a cause of data loss in traditional magnetic media, on the longevity of data in DNA data storage pools. We develop a mass action kinetics model to estimate the rate of damage accumulation in DNA strands due to neutron interactions with both nucleotides and residual water molecules, then utilize the model to evaluate the effect several design parameters of a typical DNA data storage scheme have on expected data longevity. Finally, we experimentally validate our model by exposing dried DNA samples to different levels of neutron irradiation and analyzing the resulting error profile. Our results show that particle radiation is not a significant contributor to data loss in DNA data storage pools under typical storage conditions., (© 2024. The Author(s).)
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- 2024
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5. Scaling DNA data storage with nanoscale electrode wells.
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Nguyen BH, Takahashi CN, Gupta G, Smith JA, Rouse R, Berndt P, Yekhanin S, Ward DP, Ang SD, Garvan P, Parker HY, Carlson R, Carmean D, Ceze L, and Strauss K
- Abstract
Synthetic DNA is an attractive medium for long-term data storage because of its density, ease of copying, sustainability, and longevity. Recent advances have focused on the development of new encoding algorithms, automation, preservation, and sequencing technologies. Despite progress in these areas, the most challenging hurdle in deployment of DNA data storage remains the write throughput, which limits data storage capacity. We have developed the first nanoscale DNA storage writer, which we expect to scale DNA write density to 25 × 10
6 sequences per square centimeter, three orders of magnitude improvement over existing DNA synthesis arrays. We show confinement of DNA synthesis to an area under 1 square micrometer, parallelized over millions of nanoelectrode wells and then successfully write and decode a message in DNA. DNA synthesis on this scale will enable write throughputs to reach megabytes per second and is a key enabler to a practical DNA data storage system.- Published
- 2021
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6. An integrated biorefinery concept for conversion of sugar beet pulp into value-added chemicals and pharmaceutical intermediates.
- Author
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Cárdenas-Fernández M, Bawn M, Hamley-Bennett C, Bharat PKV, Subrizi F, Suhaili N, Ward DP, Bourdin S, Dalby PA, Hailes HC, Hewitson P, Ignatova S, Kontoravdi C, Leak DJ, Shah N, Sheppard TD, Ward JM, and Lye GJ
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- Beta vulgaris chemistry, Carbohydrates chemistry, Pharmaceutical Preparations chemistry, Beta vulgaris metabolism, Carbohydrates biosynthesis, Pharmaceutical Preparations metabolism
- Abstract
Over 8 million tonnes of sugar beet are grown annually in the UK. Sugar beet pulp (SBP) is the main by-product of sugar beet processing which is currently dried and sold as a low value animal feed. SBP is a rich source of carbohydrates, mainly in the form of cellulose and pectin, including d-glucose (Glu), l-arabinose (Ara) and d-galacturonic acid (GalAc). This work describes the technical feasibility of an integrated biorefinery concept for the fractionation of SBP and conversion of these monosaccharides into value-added products. SBP fractionation is initially carried out by steam explosion under mild conditions to yield soluble pectin and insoluble cellulose fractions. The cellulose is readily hydrolysed by cellulases to release Glu that can then be fermented by a commercial yeast strain to produce bioethanol at a high yield. The pectin fraction can be either fully hydrolysed, using physico-chemical methods, or selectively hydrolysed, using cloned arabinases and galacturonases, to yield Ara-rich and GalAc-rich streams. These monomers can be separated using either Centrifugal Partition Chromatography (CPC) or ultrafiltration into streams suitable for subsequent enzymatic upgrading. Building on our previous experience with transketolase (TK) and transaminase (TAm) enzymes, the conversion of Ara and GalAc into higher value products was explored. In particular the conversion of Ara into l-gluco-heptulose (GluHep), that has potential therapeutic applications in hypoglycaemia and cancer, using a mutant TK is described. Preliminary studies with TAm also suggest GluHep can be selectively aminated to the corresponding chiral aminopolyol. The current work is addressing the upgrading of the remaining SBP monomer, GalAc, and the modelling of the biorefinery concept to enable economic and Life Cycle Analysis (LCA).
- Published
- 2017
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7. Centrifugal partition chromatography in a biorefinery context: Optimisation and scale-up of monosaccharide fractionation from hydrolysed sugar beet pulp.
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Ward DP, Hewitson P, Cárdenas-Fernández M, Hamley-Bennett C, Díaz-Rodríguez A, Douillet N, Adams JP, Leak DJ, Ignatova S, and Lye GJ
- Subjects
- Centrifugation, Hexuronic Acids isolation & purification, Hydrolysis, Pectins chemistry, Reproducibility of Results, Beta vulgaris chemistry, Chemical Fractionation methods, Chromatography, Liquid methods, Monosaccharides isolation & purification
- Abstract
The isolation of component sugars from biomass represents an important step in the bioprocessing of sustainable feedstocks such as sugar beet pulp. Centrifugal partition chromatography (CPC) is used here, as an alternative to multiple resin chromatography steps, to fractionate component monosaccharides from crude hydrolysed sugar beet pulp pectin. CPC separation of samples, prepared in the stationary phase, was carried out using an ethanol: ammonium sulphate (300gL
-1 ) phase system (0.8:1.8v:v) in ascending mode. This enabled removal of crude feedstream impurities and separation of monosaccharides into three fractions (l-rhamnose, l-arabinose and d-galactose, and d-galacturonic acid) in a single step. Throughput was improved three-fold by increasing sample injection volume, from 4 to 16% of column volume, with similar separation performance maintained in all cases. Extrusion of the final galacturonic acid fraction increased the eluted solute concentration, reduced the total separation time by 24% and removed the need for further column regeneration. Reproducibility of the separation after extrusion was validated by using multiple stacked injections. Scale-up was performed linearly from a semi-preparative 250mL column to a preparative 950mL column with a scale-up ratio of 3.8 applied to mobile phase flow rate and sample injection volume. Throughputs of 9.4gL-1 h-1 of total dissolved solids were achieved at the preparative scale with a throughput of 1.9gL-1 h-1 of component monosaccharides. These results demonstrate the potential of CPC for both impurity removal and target fractionation within biorefinery separations., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)- Published
- 2017
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8. Body size drives allochthony in food webs of tropical rivers.
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Jardine TD, Rayner TS, Pettit NE, Valdez D, Ward DP, Lindner G, Douglas MM, and Bunn SE
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- Animals, Body Size, Ecosystem, Fishes, Food Chain, Rivers
- Abstract
Food web subsidies from external sources ("allochthony") can support rich biological diversity and high secondary and tertiary production in aquatic systems, even those with low rates of primary production. However, animals vary in their degree of dependence on these subsidies. We examined dietary sources for aquatic animals restricted to refugial habitats (waterholes) during the dry season in Australia's wet-dry tropics, and show that allochthony is strongly size dependent. While small-bodied fishes and invertebrates derived a large proportion of their diet from autochthonous sources within the waterhole (phytoplankton, periphyton, or macrophytes), larger animals, including predatory fishes and crocodiles, demonstrated allochthony from seasonally inundated floodplains, coastal zones or the surrounding savanna. Autochthony declined roughly 10% for each order of magnitude increase in body size. The largest animals in the food web, estuarine crocodiles (Crocodylus porosus), derived ~80% of their diet from allochthonous sources. Allochthony enables crocodiles and large predatory fish to achieve high biomass, countering empirically derived expectations for negative density vs. body size relationships. These results highlight the strong degree of connectivity that exists between rivers and their floodplains in systems largely unaffected by river regulation or dams and levees, and how large iconic predators could be disproportionately affected by these human activities.
- Published
- 2017
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9. Centrifugal partition chromatography in a biorefinery context: Separation of monosaccharides from hydrolysed sugar beet pulp.
- Author
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Ward DP, Cárdenas-Fernández M, Hewitson P, Ignatova S, and Lye GJ
- Subjects
- Arabinose isolation & purification, Galactose isolation & purification, Hydrolysis, Pectins isolation & purification, Beta vulgaris chemistry, Countercurrent Distribution methods, Monosaccharides isolation & purification
- Abstract
A critical step in the bioprocessing of sustainable biomass feedstocks, such as sugar beet pulp (SBP), is the isolation of the component sugars from the hydrolysed polysaccharides. This facilitates their subsequent conversion into higher value chemicals and pharmaceutical intermediates. Separation methodologies such as centrifugal partition chromatography (CPC) offer an alternative to traditional resin-based chromatographic techniques for multicomponent sugar separations. Highly polar two-phase systems containing ethanol and aqueous ammonium sulphate are examined here for the separation of monosaccharides present in hydrolysed SBP pectin: l-rhamnose, l-arabinose, d-galactose and d-galacturonic acid. Dimethyl sulfoxide (DMSO) was selected as an effective phase system modifier improving monosaccharide separation. The best phase system identified was ethanol:DMSO:aqueous ammonium sulphate (300gL(-1)) (0.8:0.1:1.8, v:v:v) which enabled separation of the SBP monosaccharides by CPC (200mL column) in ascending mode (upper phase as mobile phase) with a mobile phase flow rate of 8mLmin(-1). A mixture containing all four monosaccharides (1.08g total sugars) in the proportions found in hydrolysed SBP was separated into three main fractions; a pure l-rhamnose fraction (>90%), a mixed l-arabinose/d-galactose fraction and a pure d-galacturonic acid fraction (>90%). The separation took less than 2h demonstrating that CPC is a promising technique for the separation of these sugars with potential for application within an integrated, whole crop biorefinery., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2015
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10. Does flood rhythm drive ecosystem responses in tropical riverscapes?
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Jardine TD, Bond NR, Burford MA, Kennard MJ, Ward DP, Bayliss P, Davies PM, Douglas MM, Hamilton SK, Melack JM, Naiman RJ, Pettit NE, Pusey BJ, Warfe DM, and Bunn SE
- Subjects
- Animals, Australia, Climate Change, Mexico, Rivers, South America, Biodiversity, Birds physiology, Ecosystem, Fishes physiology, Floods, Forests
- Abstract
Biotic communities are shaped by adaptations from generations of exposure to selective pressures by recurrent and often infrequent events. In large rivers, floods can act as significant agents of change, causing considerable physical and biotic disturbance while often enhancing productivity and diversity. We show that the relative balance between these seemingly divergent outcomes can be explained by the rhythmicity, or predictability of the timing and magnitude, of flood events. By analyzing biological data for large rivers that span a gradient of rhythmicity in the Neotropics and tropical Australia, we find that systems with rhythmic annual floods have higher-fish species richness, more stable avian populations, and elevated rates of riparian forest production compared with those with arrhythmic flood pulses. Intensification of the hydrological cycle driven by climate change, coupled with reductions in runoff due to water extractions for human use and altered discharge from impoundments, is expected to alter the hydrologic rhythmicity of floodplain rivers with significant consequences for both biodiversity and productivity.
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- 2015
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11. Vitamin E levels in soybean (Glycine max (L.) Merr.) expressing a p-hydroxyphenylpyruvate gene from oat (Avena sativa L.).
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Kramer CM, Launis KL, Traber MG, and Ward DP
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- 4-Hydroxyphenylpyruvate Dioxygenase metabolism, Avena genetics, Gene Expression, Nutritive Value, Plant Proteins metabolism, Plants, Genetically Modified genetics, Plants, Genetically Modified metabolism, Seeds chemistry, Seeds genetics, Seeds metabolism, Glycine max chemistry, Glycine max genetics, Vitamin E biosynthesis, 4-Hydroxyphenylpyruvate Dioxygenase genetics, Avena enzymology, Plant Proteins genetics, Plants, Genetically Modified chemistry, Glycine max metabolism, Vitamin E analysis
- Abstract
The enzyme p-hydroxyphenylpyruvate dioxygenase (HPPD) is ubiquitous in plants and functions in the tyrosine catabolic pathway, resulting in the formation of homogentisate. Homogentisate is the aromatic precursor of all plastoquinones and tocochromanols, including tocopherols and tocotrienols. Soybean (Glycine max (L.) Merr.) has been genetically modified to express the gene avhppd-03 that encodes the protein AvHPPD-03 derived from oat (Avena sativa L.). The AvHPPD-03 isozyme has an inherent reduced binding affinity for mesotrione, a herbicide that inhibits the wild-type soybean HPPD enzyme. Expression of avhppd-03 in soybean plants confers a mesotrione-tolerant phenotype. Seeds from three different avhppd-03-expressing soybean events were quantitatively assessed for content of eight vitamin E isoforms. Although increased levels of two tocopherol isoforms were identified for each of the three soybean events, they were within, or not substantially different from, the ranges of these isoforms found in nontransgenic soybean varieties. The increases of these tocopherols in the avhppd-03-expressing soybean events may have a slight benefit with regard to vitamin E nutrition but, given the commercial processing of soybeans, are unlikely to have a material impact on human nutrition with regard to vitamin E concentrations in soybean oil.
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- 2014
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12. Assessment of genetically modified soybean in relation to natural variation in the soybean seed metabolome.
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Clarke JD, Alexander DC, Ward DP, Ryals JA, Mitchell MW, Wulff JE, and Guo L
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- Cluster Analysis, Computational Biology, Plants, Genetically Modified, Metabolome, Metabolomics, Seeds genetics, Seeds metabolism, Glycine max genetics, Glycine max metabolism
- Abstract
Genetically modified (GM) crops currently constitute a significant and growing part of agriculture.An important aspect of GM crop adoption is to demonstrate safety; identifying differences in end points with respect to conventional crops is a part of the safety assessment process [corrected]. Untargeted metabolomics has the ability to profile diverse classes of metabolites and thus could be an adjunct for identification of differences between the GM crop and its conventional counterpart [corrected].To account for environmental effects and introgression of GM traits into diverse genetic backgrounds, we propose that the assessment for GM crop metabolic composition should be understood within the context of the natural variation for the crop. Using a non-targeted metabolomics platform, we profiled 169 metabolites and established their dynamic ranges from the seeds of 49 conventional soybean lines representing the current commercial genetic diversity. We further demonstrated that the metabolome of a GM line had no significant deviation from natural variation within the soybean metabolome, with the exception of changes in the targeted engineered pathway.
- Published
- 2013
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13. Consumer-resource coupling in wet-dry tropical rivers.
- Author
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Jardine TD, Pettit NE, Warfe DM, Pusey BJ, Ward DP, Douglas MM, Davies PM, and Bunn SE
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- Animals, Biofilms, Carbon chemistry, Carbon metabolism, Carbon Isotopes analysis, Diet, Gastrointestinal Contents chemistry, Invertebrates chemistry, Northern Territory, Queensland, Regression Analysis, Seasons, Species Specificity, Tropical Climate, Water Movements, Western Australia, Fishes, Food Chain, Rivers
- Abstract
1. Despite implications for top-down and bottom-up control and the stability of food webs, understanding the links between consumers and their diets remains difficult, particularly in remote tropical locations where food resources are usually abundant and variable and seasonal hydrology produces alternating patterns of connectivity and isolation. 2. We used a large scale survey of freshwater biota from 67 sites in three catchments (Daly River, Northern Territory; Fitzroy River, Western Australia; and the Mitchell River, Queensland) in Australia's wet-dry tropics and analysed stable isotopes of carbon (δ(13) C) to search for broad patterns in resource use by consumers in conjunction with known and measured indices of connectivity, the duration of floodplain inundation, and dietary choices (i.e. stomach contents of fish). 3. Regression analysis of biofilm δ(13) C against consumer δ(13) C, as an indicator of reliance on local food sources (periphyton and detritus), varied depending on taxa and catchment. 4. The carbon isotope ratios of benthic invertebrates were tightly coupled to those of biofilm in all three catchments, suggesting assimilation of local resources by these largely nonmobile taxa. 5. Stable C isotope ratios of fish, however, were less well-linked to those of biofilm and varied by catchment according to hydrological connectivity; the perennially flowing Daly River with a long duration of floodplain inundation showed the least degree of coupling, the seasonally flowing Fitzroy River with an extremely short flood period showed the strongest coupling, and the Mitchell River was intermediate in connectivity, flood duration and consumer-resource coupling. 6. These findings highlight the high mobility of the fish community in these rivers, and how hydrological connectivity between habitats drives patterns of consumer-resource coupling., (© 2011 The Authors. Journal of Animal Ecology © 2011 British Ecological Society.)
- Published
- 2012
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14. Partial factor IXa inhibition with TTP889 for prevention of venous thromboembolism: an exploratory study.
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Eriksson BI, Dahl OE, Lassen MR, Ward DP, Rothlein R, Davis G, and Turpie AG
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- Adult, Aged, Aged, 80 and over, Double-Blind Method, Female, Fibrinolytic Agents pharmacology, Hemorrhage, Humans, Male, Middle Aged, Phlebography methods, Treatment Outcome, Factor IXa antagonists & inhibitors, Venous Thromboembolism prevention & control, Venous Thrombosis metabolism, Venous Thrombosis prevention & control
- Abstract
Background: Inhibitors of factor (F) IXa show potent antithrombotic activity with a low risk of bleeding in preclinical models. We investigated the anticoagulant potential of oral TTP889, a small molecule that inhibits up to 90% of FIXa activity at therapeutic doses, using a clinical model of extended prophylaxis in hip fracture surgery (HFS)., Methods: In this multicenter, randomized, double-blind study, 261 patients received oral TTP889 (300 mg once daily) or placebo starting 6-10 days after HFS, and standard thromboprophylaxis for 5-9 days. Treatment was continued for 3 weeks and all patients then underwent mandatory bilateral venography. The primary efficacy outcome was venous thromboembolism (VTE; venographic or symptomatic deep vein thrombosis or pulmonary embolism) during treatment, and it was evaluated centrally by an independent adjudication panel. The main safety outcome was bleeding (major, clinically relevant non-major, and minor events)., Results: Two hundred and twelve patients with an evaluable venogram were included in the efficacy analysis. The primary efficacy outcome occurred in 32.1% (35/109) of patients who had been allocated TTP889, and 28.2% (29/103) of patients on placebo (P = 0.58). There were no major bleeding events, and only two clinically relevant non-major bleeding events with TTP889., Conclusion: Partial FIXa inhibition with TTP889 300 mg daily was not effective for extended prevention of VTE after standard prophylaxis for up to 9 days. Coupled with the low incidence of bleeding episodes, this suggests a lack of antithrombotic potential. Further investigation of TTP889 in different clinical settings is needed. (Clinical trial registration information URL: http://www.clinicaltrials.gov. Unique identifier: NCT00119457).
- Published
- 2008
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15. Molecular analysis of enterococcal loci involved in novel catabolic pathways.
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Claiborne A, Buckley E, Parsonage D, Ross RP, and Ward DP
- Subjects
- Amino Acid Sequence, Bacterial Outer Membrane Proteins genetics, Bacterial Outer Membrane Proteins metabolism, Energy Metabolism, Genes, Bacterial, Genetic Linkage, Glycerol metabolism, Glycerol Kinase genetics, Glycerol Kinase metabolism, Glycerolphosphate Dehydrogenase genetics, Glycerolphosphate Dehydrogenase metabolism, Molecular Sequence Data, Oxidation-Reduction, Aquaporins, Enterococcus genetics, Enterococcus metabolism, Escherichia coli Proteins
- Published
- 1995
16. Chronic phencyclidine induced changes in rat central cholinergic receptor regulation.
- Author
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Ward DP and Trevor AJ
- Subjects
- Animals, Corpus Striatum metabolism, Hippocampus metabolism, Male, Rats, Time Factors, Brain drug effects, Phencyclidine pharmacology, Receptors, Cholinergic drug effects
- Published
- 1981
17. Metabolism of phencyclidine. The role of iminium ion formation in covalent binding to rabbit microsomal protein.
- Author
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Ward DP, Trevor AJ, Kalir A, Adams JD, Baillie TA, and Castagnoli N Jr
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- Animals, Binding Sites drug effects, Chromatography, High Pressure Liquid, Gas Chromatography-Mass Spectrometry, In Vitro Techniques, Male, Rabbits, Sodium Cyanide pharmacology, Imines metabolism, Microsomes, Liver metabolism, Phencyclidine metabolism, Protein Binding
- Abstract
Incubation of phencyclidine (PCP) with rabbit liver microsomes and Na14CN resulted in the metabolically dependent formation of a 14C-labeled cyano adduct of the drug. After isolation by HPLC, this compound was identified as the alpha-aminonitrile [1-(1-phenylcyclohexyl)-2-cyanopiperidine] derivative of PCP by use of chemical-ionization and gas-chromatographic coupled electron-impact mass spectrometry. Synthetic alpha-aminonitrile exhibited identical chemical properties and comigrated in HPLC and GLC with the metabolism derived cyano adduct. Molecular identification of the adduct formed by cyanide trapping provided evidence for the formation of an iminium ion during PCP metabolism. Quantitative estimation by HPLC demonstrated that the alpha-aminonitrile accounted for over 50% of the PCP metabolized in 30 min by hepatic microsomes in vitro. Metabolism-dependent covalent binding of [3H]PCP to rabbit liver microsomal proteins was inhibited by cyanide ion in a concentration-dependent manner with an IC50 value of 57 microM. The concentrations of cyanide ion used in these experiments did not significantly inhibit the metabolism of PCP. These results support our suggestions that iminium ion formation may represent an important intermediary step in the metabolism of PCP and that such a reactive electrophilic species may be capable of covalent interactions with nucleophilic groupings on microsomal macromolecules.
- Published
- 1982
18. Radioimmunoassay for phencyclidine: application to kinetic analysis in the rat.
- Author
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Ward DP and Trevor AJ
- Subjects
- Animals, Brain metabolism, Chromatography, Gas, Kinetics, Male, Phencyclidine immunology, Radioimmunoassay methods, Rats, Phencyclidine analysis
- Published
- 1980
- Full Text
- View/download PDF
19. Evaluation of the systemic toxicity of coal liquefaction-derived materials following repeated dermal exposure in the rabbit.
- Author
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McKee RH, Kapp RW Jr, and Ward DP
- Subjects
- Administration, Topical, Animals, Blood Proteins metabolism, Body Weight drug effects, Cholesterol blood, Enzymes blood, Female, Hydrocarbons toxicity, Irritants, Male, Oils toxicity, Organ Size drug effects, Rabbits, Solvents, Coal toxicity
- Abstract
The subchronic toxicity of two materials produced by the EDS direct coal liquefaction process was investigated using adult New Zealand white rabbits as the test species. Recycle solvent (RS: 204-427 degrees C) and fuel oil (FO: 204-538 degrees C) were applied to the intact dorsal surface of rabbits, 5 days per week for 4 weeks. Materials were applied as suspensions (2.5 and 10.0 g 100 ml-1) in white oil. White oil alone was administered to concurrent control groups. Both RS and FO elicited gross signs of toxicity including severe dermal irritation, loss of body weight (16-25%) and mortality (4/20 in the high-dose group treated with RS). Systemic effects included liver enlargement as evidenced by histologic findings of diffuse hepatocytomegaly, cytoplasmic degeneration and hepatocellular vacuolation as well as elevated serum cholesterol. There was also evidence of testicular, seminal vesicle and thymic atrophy. More pronounced effects were apparent in the high-dose groups. Testes and epididymides from four of the five FO-treated male rabbits were unremarkable at the microscopic level. The testes, epididymides and seminal vesicles of the fifth animal were atrophic. Three of ten RS treated rabbits showed testicular atrophy associated with hypospermatogenesis in the testes, aspermia in the epididymides and vesiculitis in the seminal vesicles. Four additional animals showed evidence of seminal vesicle atrophy. The liver enlargement was probably due to compensatory metabolism; however, exposure to similar materials at higher levels has resulted in liver toxicity. Thymic and testicular atrophy may have been a secondary response to dermal irritation, stress or body weight loss.
- Published
- 1985
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20. Testicular hypoplasia and XXY sex chromosome complement in two rams: the ovine counterpart of Klinefelter's syndrome in man.
- Author
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Bruere AN, Marshall RB, and Ward DP
- Subjects
- Animals, Karyotyping, Male, Sex Chromatin, Sheep, Spermatozoa, Testis pathology, Klinefelter Syndrome veterinary, Sheep Diseases genetics, Testicular Diseases veterinary
- Published
- 1969
- Full Text
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21. Therapeutic utilization of the physiological reserves.
- Author
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WARD DP
- Subjects
- Humans, Physiology
- Published
- 1949
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