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o Byrnes CA. Cystic Fibrosis Bronchoalveolar Lavage Study - National Cystic Fibrosis Seminar February 2003 - invited presentation. o Howie S, Voss L, Grimwood K, Byrnes CA. Tuberculosis disease in New 7*aland Children. American Thoracic Meeting & American Journal of Respiratory & Critical Care Medicine 2003;163 (5) :4854. o Twiss J, Byrnes CA. Paediatric bronchiectasis: longitudinal lung function and comparison with cystic fibrosis. New Zealand Paediatric Society Annual Conference 2003. Highly commended award. o Twiss J, Byrnes CA. Longitudinal lung function. Thoracic Society of Australia & New Zealand2003. o Wainwright C, Cooper P, Carlin J, James M, Armstrong D, Robertson I, Cooper D, Whitehead B, Byrnes C, Francis P, Robertson C. Early infection with pseudomonas aeruginosa can be effectively cleared in young children with cystic fibrosis. Australian Cystic Fibrosis Conference 2003. o Byrnes CA. Asthma Medications - New Tnaland Paediatric Update 2002 - invited presentation. r Howie S, Voss L, Grimwood K, Byrnes CA. Tuberculosis disease in New Tr,aland Children. New Zraland Paediatric Society Annual Conference 2002. o Wainwright C, Carlin J, Cooper P, Byrnes C, Whitehead B, Martin J, Cooper D, Armstong D, Robertson C. Early infection with pseudomonas can be cleared in young children with cystic fibrosis - North American Cystic Fibrosis Meeting 2002 Pediatic Pulmonology Supplement 24: 357 . o Vogel AM. Moodabe K, Aish H, Campanella S, Byrnes CA. Implementation of guidelines for the management of cough and wheeze in the I't year of life in general practice. New Zealand Paedi atric Society Annual Meeting 200L. o Jaksic M, Asher MI, Byrnes CA. Streptokinase in the Management of Empyema. American Thoracic Meeting & American Journal of Respiratory & Critical Care Medicine 2001; 163 (5): A854. e Edwards EA, Asher MI, Metcalfe R, Byrnes CA. Non-cystic bronchiectasis - correlation of high resolution CT scan and chest x-ray scores with clinical evaluation. American Thoracic Meeting & American Journal of Respiratory & Critical Care Medicine 2001; 163 (5): A854. o Edwards EA. Byrnes CA. Temperature control is vital for the measurement of cilia beat frequency when establishing a hospital protocol. European Respiratory Meeting & European Respiratory Journal 2001;18: 300s. 269
o Byrnes CA. Paediatric fibreoptic bronchoscopy - New Tnaland Paediatric Society Annual Meeting 2001. o Byrnes CA. Screening for respiratory ciliary dysfunction - New 7*,aland Paediatric Society Annual Meeting 200I. r Edwards EA, Metcalfe R, Asher MI, Byrnes CA. Bronchiectasis - Correlation of high resolution CT scan and chest x-ray scores with clinical evaluation in 52 children. New Tnaland Paedi atri c S oci ety Ann u al Conference 2000. o Edwards EA, Douglas C, Broome S, Jensen C, Byrnes CA. Exhaled nitric oxide (NO) and ciliary beat frequency (CBF) in normal and bronchiectatic children. New Zealand Thoracic Society 2000. o Edwards EA, Metcalfe R, Asher MI, Byrnes CA. Bronchiectasis - Correlation of high resolution CT scan and chest x-ray scores with clinical evaluation in 52 children. New 7*aland Paediatric Society Annual Conference 2000. o Byrnes CA. Home oxygen in children - National Respiratory Meeting 2000 - invited presentation. o Byrnes CA. Infection control in children with cystic fibrosis - National NZ Respiratory Meeting 2000 - invited presentation. o Byrnes CA. Obstructive sleep apnea - New 7*aland Paediatric Update 2000 - invited presentation. o Byrnes CA. Management of pleural effusions - New 7-ealand Paediatric Update 2000 - invited presentation. o Byrnes CA, Barnes PJ, Bush A. Salmeterol trial in asthmatic children - American Thoracic Society Annual Scientific Meeting 1999. Abstracts and poster presentations: o McNamara DG, Byrnes CA, Rutland MD. Development of a technique to measure mucociliary clearance in children with tracheostomies. Thoracic Society of Australia & New Zealand Annual Scientific Meeting, May 2005. o McMorran B, James A, Armstrong D, Cooper P, Carlin J, Martin J, Robertson I, Cooper D, Whitehead B, Byrnes C, Francis P, Robertson C, Wainwright C, Wainwright B. Proteomic comparisons in cystic fibrosis lung lavage fluid using ProteinChip@ technology. North American Annual Cystic Fibrosis Conference, October 2W3. r Butler SA, Twiss J, Byrnes CA. Bronchiectasis outreach - a new initiative in New 7*aland. Fifth National Paediatric Physiotherapy Conference, Australasia, 2003. 270
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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
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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,
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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
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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 and 290: Edwards EA, Douglas C, Broome S, Je
Page 291: o Cass Byrnes & Nicky Holt. "Drugs
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
Page 341 and 342: 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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