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o Howie S, Voss L, Baker M, Calder L, Grimwood K, Byrnes C. Tuberculosis in New Tnaland, 1992-200I: a resurgence. Archives of Disease in Childhood 2005; 90: II57- 1161. r Gillies J, Brown J, Byrnes C, Farell A, Graham D. PHARMAC and ventolin in New Tlaland. New Zealand Medical Journal August 2005; Ll8:122O. o Twiss J, Metcalfe R, Edwards E, Byrnes C. New Zealand national incidence of bronchiectasis "too high" for a developed country. Archives of Disease in Childhood 2005;90(7): 737-740. o Twiss J, Byrnes CA, Johnson R, Holland D. Nebulised gentamicin - suitable for childhood bronchiectasis. International Journal of Pharmaceutics 2OO5;295: ll3-119 o Edwards EA, Douglas C, Broome S, Kolbe J, Jensen CG, Dewar A, Bush A, Byrnes CA. Nitric oxide levels and ciliary beat frequency in indigenous New Zealand children. Pediatric Pulmonolo gy 2005; 39: 238-246. r Edwards EA, Metcalfe R, Milne DG, Thompson J, Byrnes CA. Retrospective review of children presenting with non cystic fibrosis bronchiectasis: HRCT features and clinical rel ationships. Pedi atric Pulmonolo gy 20O3 ; 36: 87 -93. o Edwards EA, Asher MI, Byrnes CA. Paediatric bronchiectasis in the 2l't century: experience of a tertiary childrens hospital in New T.rualand. Journal of Paediatric and Child Health 2003; 39: 1 I L-117 . o Vogel A, knnon D, Broadbent R, Byrnes CA, Grimwood K, Mildenhall L, Richardson V, Rowley S. Palvimuzab prophylaxis of respiratory syncytial virus infection in high risk infants. Journal of Paediatric and Child Health 2OO2;38: 550-554. o Edwards EA, Butler SA, Byrnes CA. Paediatric non cystic fibrosis bronchiectasis - recognition and management. New Ethicals Journal 2OO2; November: 58-65 (invited article). o Massie J, Poplawski N, Wilcken B, Goldblatt J, Byrnes C, Robertson C. Intron-8 polythymidine sequence in Australasian individuals with CF mutations RllTH and Rll7C. European Respiratory Journal 2001 L7 1195-1200. o Byrnes CA, Shrewsbury S, Barnes PJ, Bush A. Salmeterol in Paediatric Asthma. Thorax 2000; 55:780-784. o Edwards E, Byrnes CA. Humidification difficulties in two tracheostomised children, Journal of Anaesthetic and Intensive Care 1999; 27:656-658. 267
o Cass Byrnes & Nicky Holt. "Drugs used in Cystic Fibrosis". Medicines for Children. British Paediatric Formulatory I't Edition, published by the Royal College of Paediatrics and Child Health 1999. Other presentations and published abstracts: International Meetings: o Byrnes CA. Pearls: Non-Cystic Fibrosis Bronchiectasis - 7fr International Congress on Pediatric Pulmonology, Montreal, Canada July 2006 - invited presentation. o Byrnes CA. Lung function accreditation guidelines - Australasian Paediatric Respiratory Group Annual Scientific Meeting 2004 - invited presentation. o Byrnes CA. Lung function and lung function accreditation guidelines - Australasian Paediatric Respiratory Group Annual Scientific Meeting 2W3 - invited presentation. o Bynes CA. Bronchiectasis - Australasian Paediatric Respiratory Group Annual Scientific Meeting 2OO2 - invited presentation. . Byrnes CA, Barnes PJ, Bush A. Salmeterol trial in asthmatic children - American Thoracic Society Annual Scientific Meeting 1999. National Meetings: o Byrnes CA. Australia and New 7*,aland Cystic Fibrosis Bronchoalveolar Lavage - National Respiratory Meeting 2W7 - invited presentation. o Byrnes CA. Paediatric workshop - Standards of Care in Cystic Fibrosis in New 7*aland - National Respiratory Meeting 2007- invited presentation. o Byrnes CA. Paediatric cases workshop - National Respiratory Meeting L999-2W6 - invited presentation. o Cheney JL, Carlin J, Cooper P, Byrnes C, Grimwood K, Armstrong D, Martin J, Dakin C, Robertson C, Whitehead B, Francis P, Vidmar S, Wainwright CE. Adverse events associated with flexible bronchoscopy and bronchoalveolar lavage in young children with cystic fibrosis. North American Cystic Fibrosis Conference 2006. r Wainwright CE, Carlin J, Cooper P, Byrnes C, Martin J, Grimwood K,, Armstrong D, Francis P, Dakin C, Whitehead B, Carter R, Vidmar S, Cheney J, Tiddens H, Fink M, Robertson C. Australasian Cystic Fibrosis BAL study analysis. North American Cystic Fibrosis Conference 200,6. o Byrnes CA. Pseudomonas aeruginosa - management of ltt infection in children with cystic fibrosis - National Respiratory Meeting 2003 - invited presentation. 268
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UNIVERSITV OF AUCKI'AND Abstract -
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There was no significant difference
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This is Dedicated: Dedication To th
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New Zealand The Paediatric Departme
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Contents Abstract ........tr Dedica
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6.5.4 The subjects............... .
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XIV
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List of Figures Figure l.l: Top l0
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List of Abbreviations ABPA allergic
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LADA N*N* dimethyl L-arginine LFA1
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t}ryem(eNoS)Typeltrendothelialnifti
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area, some of it has been expanded
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In addition, both of these groups a
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studies conducted throughout the Un
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Video clips of infants with a varie
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the Paediatric Society of New 7*ala
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inhaled anti-cholinergic agents and
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ecommended to monitor asthma at hom
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improvement to 70Vo PEF would have
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Furthermore, investigators have als
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poorer predictor of a diagnosis of
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Bronsky et al. 1998), and a long-te
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SIGN guideline (SIGN 2005) stated "
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In brief, the human airway can be d
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The ability to biopsy has led to st
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small proportion of cells recovered
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methodology of sputum induction and
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et al. 1999; Giannini, Di Franco et
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over a six month treatment prograrn
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There are other studies suggesting
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So is induced sputum in adults and
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asymptomatic patients independent o
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onchial hyper-responsiveness (Reich
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led to research which looked for le
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analyser machines. This thesis pres
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The pollution of the 'great smog of
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adults greater than 65 years (Ostro
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levels compared to those children l
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More recently 'Air Quality Indexes'
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acetylcholine. These were known to
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cyclase does not produce significan
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Garthwaite l99l), and the non adren
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significant complication, this trea
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locus for the enzyme is a susceptib
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NO synthesis and in so doing blocke
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3.1 Chapter 3: The synthesis, react
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BHa = tetrahyrobiopterin, FAD = fla
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(Knowles, McWeeny et al. 1974) and
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more potent at low oxygen tensions
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toxic products such as isoprostanes
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Figure 3.3: The nitric oxide syntha
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providing NO as a neurotransmitter
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The enzyme of this second pathway -
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inappropriate production from comme
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Nicotinamide adenosine dinucleotide
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enzyme and are competitively revers
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4.1 Introduction Chapter 4: Methods
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4.4 Nitrite and nitrate The measure
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insensitive (Braker and Mossman 197
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A group of instruments have been de
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The original group demonstrated tha
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equired it. For example, there was
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helium for 30 minutes to remove Oz.
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(Postlethwait and Bidani 1990; Post
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is set at 5ppm (AIHA 1966) based on
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5.1 Chapter 5: Methodological asses
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wanted to compare the patterns of e
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in different colours that became th
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an advisor for this work and main s
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Delay time: the time between turnin
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led to an increased water content t
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Chapter 6: Methodological studies o
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pulmonary circulation appeared to c
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al found levels of 10.3ppb compared
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Authors and Pap€r Sublect numbers
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only those measured by mouth or low
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6. Check that the pens work. Fill w
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keys but it is currently in the mid
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Calibration pressures: the test por
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T-piece: tO The first figure shows
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the rotameter. Tracings of each par
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Figure 6.6: Mean exhaled NO levels
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NO and COz results from single exha
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6.6.4 (iii) Comparison of exhaled n
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Figure 6.11b: COz levels at peak NO
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I also considered whether the diffe
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the direct to the indirect method l
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need for methodological experiments
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The exhalations were carried out in
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Figure 7.2: Example of the tracing
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7.4.4 Results There was an increase
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Table 7.3: NO, COz and duration of
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The second set of exhalations invol
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Figure 7.6: Photographs of the chan
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Table 7.5: Exhaled NO results with
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the NO concentrations taken pre and
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Figure 7.10: Hyperbolic relationshi
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pressure over the likely range enco
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subjects with respiratory disease,
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8.1 Chapter 8: Exhaled nitric oxide
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standard error of the mean (SEM), s
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T-piece sampling system to analyser
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Figure 8.2a: Comparison of peak exh
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if yes who? if yes who? if yes who?
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There are limitations with regard t
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significantly between research grou
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controls. Kharitinov et al reported
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direct method in asthmatic children
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Figure 8.4a: The eftect of commenci
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had last used her p2 agonist inhale
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higher level of exhaled NO at 4.9pp
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9.1 Introduction Chapter 9: Exhaled
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For the oral measurements options i
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Table 9.1: The recommended standard
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taken from the available literature
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compartment correlated with the ser
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measurement with variable expirator
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to settle. We may have been measuri
Page 239 and 240: 9.5 Off-line measurement NO determi
Page 241 and 242: (Hyde, Geigel et al. 1997; Tsoukias
Page 243 and 244: 9.6 Nasal nitric oxide measurement
Page 245 and 246: measured over two 24 hour periods,
Page 247 and 248: women who coincidently experienced
Page 249 and 250: While these cross-sectional and the
Page 251 and 252: symptoms. Steroid response was sign
Page 253 and 254: 'difficult asthma' also had higher
Page 255 and 256: season and then reduced down to bas
Page 257 and 258: of cross sectional studies with a t
Page 259 and 260: Ciabattoni et al. 2004; Petersen, A
Page 261 and 262: FEV9.5, symptom score and airways r
Page 263 and 264: Indomethacin - This medication alte
Page 265 and 266: 89Vo for PCD, and above that exclud
Page 267 and 268: This low NO occurs despite higher t
Page 269 and 270: patients were followed through one
Page 271 and 272: differences noted based on filter,
Page 273 and 274: 9.L6 Nitric oxide levels in exercis
Page 275 and 276: another study of 111 school childre
Page 277 and 278: Almost all studies used sedation, w
Page 279 and 280: peak exhaled NO production in the f
Page 281 and 282: flow and to minimize nasal contamin
Page 283 and 284: ecruit blood vessels in the lung. S
Page 285 and 286: Chapter 10: Reflections The outcome
Page 287 and 288: and I enrolled 52 asthmatic childre
Page 289: Edwards EA, Douglas C, Broome S, Je
Page 293 and 294: o Byrnes CA. Paediatric fibreoptic
Page 295 and 296: Appendix 2: Questionnaire for enrol
Page 297 and 298: Al-Ali, M. K. and P. H. Howarth (20
Page 299 and 300: Archer, S. L., P. J. Shultz, et al.
Page 301 and 302: Baraldi, E., N. M. Azzolin, et al.
Page 303 and 304: Belda, J., P. Hussack, et al. (2001
Page 305 and 306: Bongers, T. and B. R. ODriscoll (20
Page 307 and 308: Brown, G. C. and C. E. Cooper (1994
Page 309 and 310: Castro-Rodriguez, J. A., C. J. Holb
Page 311 and 312: Cockcroft, D. W., D. N. Killian, et
Page 313 and 314: de Blic, J., V. Marchac, et al. (20
Page 315 and 316: Donaldson, S. H., W. D. Bennett, et
Page 317 and 318: Emi-Miwa, M., A. Okitani, et al. (1
Page 319 and 320: Frey, U., J. Stocks, et al. (2000).
Page 321 and 322: Gershman, N. H., H. Liu, et al. (19
Page 323 and 324: Grasemann, H., E. Michler, et al. (
Page 325 and 326: Hashimoto, T., K. Minoguchi, et al.
Page 327 and 328: Holgate, S. T., D. E. Davies, et al
Page 329 and 330: Iriso, R., P. M. Mudido, et al. (20
Page 331 and 332: Jones, A. W., M. Fransson, et al. (
Page 333 and 334: Kercsmar, C. M. (2006). Wheezing in
Page 335 and 336: Kleinert, H., T. Wallerath, et al.
Page 337 and 338: Lamblin, C., P. Gosset, et al. (199
Page 339 and 340: Li, X. and J. W. Wilson (1997). "In
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Lymar, S. V. and J. K. Hurst (1996)
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Massaro, A. F., S. Mehta, et al. (1
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Miyabara, Y., R. Yanagisawa, et al.
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contribute to impaired endothelium-
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ODell, T. J., R. D. Hawkins, et al.
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Panza, J. A., C. E. Garcia, et al.
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Peters, S. P. (2006). "Safety of in
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Prieto, L., L. Bruno, et al. (2003)
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Ribbons, K. A., X. J. Zhang, et al.
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Sacco, O., R. Sale, et al. (2003).
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Sessa, W. C., K. Pritchard, et al.
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Silvestri, M., F. Sabatini, et al.
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Stamler, J. S. (1994). "Redox signa
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Stuehr, D. J., N. S. Kwon, et al. (
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Tierney, W. M., J. F. Roesner, et a
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Upchurch, G. R., G. N. Welch, et al
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Wadsworth, R., E. Stankevicius, et
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Williams, O., R. Y. Bhat, et al. (2
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Yates, D. H., S. A. Kharitonov, et
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