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151. The EuroChimerism concept for a standardized approach to chimerism analysis after allogeneic stem cell transplantation

Author

Lion, T., Watzinger, F., Preuner, S., Kreyenberg, H., Tilanus, M., de Weger, R., van Loon, J., de Vries, L., Cave, H., Acquaviva, C., Lawler, M., Crampe, M., Serra, A., Saglio, B., Colnaghi, F., Biondi, A., van Dongen, J. J. M., van der Burg, M., Gonzalez, M., Alcoceba, M., Barbany, G., Hermanson, Monica, Roosnek, E., Steward, C., Harvey, J., Frommlet, F., Bader, P., Lion, T., Watzinger, F., Preuner, S., Kreyenberg, H., Tilanus, M., de Weger, R., van Loon, J., de Vries, L., Cave, H., Acquaviva, C., Lawler, M., Crampe, M., Serra, A., Saglio, B., Colnaghi, F., Biondi, A., van Dongen, J. J. M., van der Burg, M., Gonzalez, M., Alcoceba, M., Barbany, G., Hermanson, Monica, Roosnek, E., Steward, C., Harvey, J., Frommlet, F., and Bader, P.

Abstract

Hematopoietic stem cell transplantation is becoming an increasingly important approach to treatment of different malignant and non-malignant disorders. There is thus growing demand for diagnostic assays permitting the surveillance of donor/recipient chimerism posttransplant. Current techniques are heterogeneous, rendering uniform evaluation and comparison of diagnostic results between centers difficult. Leading laboratories from 10 European countries have therefore performed a collaborative study supported by a European grant, the EuroChimerism Concerted Action, with the aim to develop a standardized diagnostic methodology for the detection and monitoring of chimerism in patients undergoing allogeneic stem cell transplantation. Following extensive analysis of a large set of microsatellite/short tandem repeat (STR) loci, the EuroChimerism (EUC) panel comprising 13 STR markers was established with the aim to optimally meet the specific requirements of quantitative chimerism analysis. Based on highly stringent selection criteria, the EUC panel provides multiple informative markers in any transplant setting. The standardized STR-PCR tests permit detection of donor-or recipient-derived cells at a sensitivity ranging between 0.8 and 1.6%. Moreover, the EUC assay facilitates accurate and reproducible quantification of donor and recipient hematopoietic cells. Wide use of the European-harmonized protocol for chimerism analysis presented will provide a basis for optimal diagnostic support and timely treatment decisions.

Published
2012
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152. Cyclosporin A and short-term methotrexate versus cyclosporin A as graft versus host disease prophylaxis in patients with severe aplastic anemia given allogeneic bone marrow transplantation from an HLA-identical sibling: results of a GITMO/EBMT randomized trial

Author

Locatelli, F., Bruno, B., Zecca, M., Van-Lint, M. T., Mccann, S., Arcese, W., Dallorso, S., Di Bartolomeo, P., FRANCA FAGIOLI, Locasciulli, A., Lawler, M., and Bacigalupo, A.

Subjects
Homologous, Graft Rejection, Adult, Male, Time Factors, Adolescent, Graft vs Host Disease, Nuclear Family, Cyclosporine, Humans, Child, Transplantation, Homologous, Immunosuppressive Agents, Child, Preschool, Drug Therapy, Combination, Histocompatibility Testing, Treatment Outcome, Anemia, Aplastic, Methotrexate, Middle Aged, Follow-Up Studies, Bone Marrow Transplantation, Female, Survival Analysis, Drug Therapy, Preschool, Transplantation, Aplastic, Anemia, Combination, Settore MED/15 - Malattie del Sangue
Abstract

A randomized trial was carried out comparing cyclosporin A (CsA) and short-term methotrexate (MTX) versus CsA alone for graft versus host disease (GVHD) prophylaxis in patients with severe aplastic anemia (SAA) undergoing allogeneic bone marrow transplantation (BMT) from a compatible sibling. Seventy-one patients (median age, 19 years; range, 4-46 years) were randomized to receive either CsA and MTX or CsA alone for the first 3 weeks after BMT. Subsequently, both groups received CsA orally, with gradual drug reduction until discontinuation 8 to 12 months after BMT. Patients randomized in both arms had comparable characteristics and received the same preparative regimen (ie, cyclophosphamide 200 mg/kg over 4 days). The median time for neutrophil engraftment was 17 days (range, 11-31 days) and 12 days (range, 4-45 days) for patients in the CsA/MTX group and the CsA alone group, respectively (P =.01). No significant difference was observed in the probability of either grade 2, grade 3, or grade 4 acute GVHD or chronic GVHD developing in the 2 groups. The Kaplan-Meier estimates of 1-year transplantation-related mortality rates for patients given either CsA/MTX or CsA alone were 3% and 15%, respectively (P =.07). With a median follow-up of 48 months from BMT, the 5-year survival probability is 94% for patients in the CsA/MTX group and 78% for those in the CsA alone group (P =. 05). These data indicate that the use of CsA with MTX is associated with improved survival in patients with SAA who receive transplants from compatible siblings. (Blood. 2000;96:1690-1697)

Published
2000

156. A chemical ionization mass spectrometer for continuous underway shipboard analysis of dimethylsulfide in near-surface seawater

Author

Saltzman, E. S., de Bruyn, W. J., Lawler, M. J., Marandino, Christa, McCormick, C. A., Saltzman, E. S., de Bruyn, W. J., Lawler, M. J., Marandino, Christa, and McCormick, C. A.

Abstract

A compact, low-cost atmospheric pressure, chemical ionization mass spectrometer ("mini-CIMS") has been developed for continuous underway shipboard measurements of dimethylsulfide (DMS) in seawater. The instrument was used to analyze DMS in air equilibrated with flowing seawater across a porous Teflon membrane equilibrator. The equilibrated gas stream was diluted with air containing an isotopically-labeled internal standard. DMS is ionized at atmospheric pressure via proton transfer from water vapor, then declustered, mass filtered via quadrupole mass spectrometry, and detected with an electron multiplier. The instrument described here is based on a low-cost residual gas analyzer (Stanford Research Systems), which has been modified for use as a chemical ionization mass spectrometer. The mini-CIMS has a gas phase detection limit of 220 ppt DMS for a 1 min averaging time, which is roughly equivalent to a seawater DMS concentration of 0.1 nM DMS at 20°C. The mini-CIMS has the sensitivity, selectivity, and time response required for underway measurements of surface ocean DMS over the full range of oceanographic conditions. The simple, robust design and relatively low cost of the instrument are intended to facilitate use in process studies and surveys, with potential for long-term deployment on research vessels, ships of opportunity, and large buoys.

Published
2009
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158. High frequency of donor chimerism after allogeneic transplantation of CD34+-selected peripheral blood cells

Author

Briones J, Urbano-Ispizua A, Lawler M, Rozman C, Gardiner N, Marín P, Salgado C, Féliz P, McCann S, and Montserrat E

Subjects
Adult, Male, Transplantation Chimera, Time Factors, Incidence, Hematopoietic Stem Cell Transplantation, Graft vs Host Disease, Antigens, CD34, Middle Aged, Hematopoietic Stem Cells, Cytapheresis, Humans, Transplantation, Homologous, Female, Prospective Studies, Bone Marrow Transplantation
Abstract

Ex vivo T cell depletion of allogeneic grafts is associated with a high (up to 80%) rate of mixed chimerism (MC) posttransplantation. The number of transplanted progenitor cells is an important factor in achieving complete donor chimerism in the T cell depletion setting. Use of granulocyte colony-stimulating factor (G-CSF) peripheral blood allografts allows the administration of large numbers of CD34+ cells. We studied the chimeric status of 13 patients who received allogeneic CD34+-selected peripheral blood progenitor cell transplants (allo-PBPCTs/CD34+) from HLA-identical sibling donors. Patients were conditioned with cyclophosphamide (120 mg/kg) and total-body irradiation (13 Gy in four fractions). Apheresis products were T cell-depleted by the immunoadsorption avidin-biotin method. The median number of CD34+ and CD3+ cells infused was 2.8x10(6)/kg (range 1.9-8.6x10(6)/kg) and 0.4x10(6)/kg (range 0.3-1x10(6)/kg), respectively. Molecular analysis of the engraftment was performed using polymerase chain reaction (PCR) amplification of highly polymorphic short tandem repeat (PCR-STR) sequences in peripheral blood samples. MC was detected in two (15%) of 13 patients. These two patients relapsed at 8 and 10 months after transplant, respectively. The remaining 11 patients showed complete donor chimerism and were in clinical remission after a maximum follow-up period of 24 months (range 6-24 months). These results were compared with those obtained in 10 patients who were treated with T cell-depleted bone marrow transplantation by means of elutriation and who received the same conditioning treatment and similar amounts of CD3+ cells (median 0.45x10(6)/kg; not significant) but a lower number of CD34+ cells (median 0.8x10(6)/kg; p = 0.001). MC was documented in six of 10 patients (60%), which was significantly higher than in the allo-PBPCT/CD34+ group (p = 0.04). We conclude that a high frequency of complete donor chimerism is achieved in patients receiving allo-PBPCT/CD34+ and that this is most likely due to the high number of progenitor cells administered.

Published
1998

160. Formation of heavy d-electron quasiparticles in Sr3Ru2O7

Author

Allan, M P, primary, Tamai, A, additional, Rozbicki, E, additional, Fischer, M H, additional, Voss, J, additional, King, P D C, additional, Meevasana, W, additional, Thirupathaiah, S, additional, Rienks, E, additional, Fink, J, additional, Tennant, D A, additional, Perry, R S, additional, Mercure, J F, additional, Wang, M A, additional, Lee, Jinho, additional, Fennie, C J, additional, Kim, E-A, additional, Lawler, M J, additional, Shen, K M, additional, Mackenzie, A P, additional, Shen, Z-X, additional, and Baumberger, F, additional

Published
2013
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163. Hygroscopicity of nanoparticles produced from homogeneous nucleation in the CLOUD experiments.

Author

J. Kim, Ahlm, L., Yli-Juuti, T., Lawler, M., Keskinen, H., Tröstl, J., Schobesberger, S., Duplissy, J., Amorim, A., Bianchi, F., Donahue, N. M., Flagan, R. C., Hakala, J., Heinritzi, M., Jokinen, T., Kürten, A., Laaksonen, A., Lehtipalo, K., Miettinen, P., and Petäjä, T.

Abstract

Sulfuric acid, amines and oxidized organics have been found to be important compounds in the nucleation and initial growth of atmospheric particles. Because of the challenges involved in determining the chemical composition of objects with very small mass, however, the properties of the freshly nucleated particles and the detailed pathways of their formation processes are still not clear. In this study, we focus on a challenging size range, i.e., particles that have grown to diameters of 10 and 15 nm following nucleation, and measure their water uptake. Water uptake is useful information for indirectly obtaining chemical composition of aerosol particles. We use a nanometer-hygroscopicity tandem differential mobility analyzer (nano-HTDMA) at subsaturated conditions (ca. 90% relative humidity at 293 K) to measure the hygroscopicity of particles during the seventh Cosmics Leaving OUtdoor Droplets (CLOUD7) campaign performed at CERN in 2012. In CLOUD7, the hygroscopicity of nucleated nanoparticles was measured in the presence of sulfuric acid, sulfuric acid-dimethylamine, and sulfuric acid-organics derived from pinene oxidation. The hygroscopicity parameter κ decreased with increasing particle size, indicating decreasing acidity of particles. No clear effect of the sulfuric acid concentration on the hygroscopicity of 10 nm particles produced from sulfuric acid and dimethylamine was observed, whereas the hygroscopicity of 15 nm particles sharply decreased with decreasing sulfuric acid concentrations. In particular, when the concentration of sulfuric acid was 5:1×106 molecules cm-3 in the gas phase, and the dimethylamine mixing ratio was 11.8 ppt, the measured of 15 nm particles was 0.31±0.01: close to the value reported for dimethylaminium sulfate (DMAS) (κDMAS ∼ 0:28). Furthermore, the difference in κ between sulfuric acid and sulfuric acid-dimethylamine experiments increased with increasing particle size. The κ values of particles in the presence of sulfuric acid and organics were much smaller than those of particles in the presence of sulfuric acid and dimethylamine. This suggests that the organics produced from α-pinene ozonolysis play a significant role in particle growth even at 10 nm sizes. [ABSTRACT FROM AUTHOR]

Published
2016
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166. Campath-1G in vivo confers a low incidence of graft-versus-host disease associated with a high incidence of mixed chimaerism after bone marrow transplantation for severe aplastic anaemia using HLA-identical sibling donors

Author

Michael R Hamblin, Marsh, Jcw, Lawler, M., Mccann, Sr, Wickham, N., Dunlop, L., Ball, S., Davies, Eg, Hale, G., Waldmann, H., and Gordonsmith, Ec

Subjects
Adult, Graft Rejection, Male, Adolescent, Antibodies, Neoplasm, Pneumonia, Viral, Graft vs Host Disease, Antibodies, Monoclonal, Humanized, Polymerase Chain Reaction, HLA Antigens, Living Donors, Humans, Family, Child, Alemtuzumab, Bone Marrow Transplantation, Chimera, Graft Survival, Anemia, Aplastic, Antibodies, Monoclonal, Middle Aged, surgical procedures, operative, Child, Preschool, Cytomegalovirus Infections, Female, Immunosuppressive Agents
Abstract

We have evaluated the effect of in vivo Campath-1G on engraftment and GVHD in 23 patients with severe aplastic anaemia transplanted from HLA-identical sibling donors. In 14 patients Campath 1g was given pre-transplant for up to 9 days in an attempt to overcome graft rejection (group 1). In nine patients Campath-1G was given pre-transplant, but also continued post-transplant until day +5 to reduce GVHD (group 2). There were three patients with late graft failure in group I following initial neutrophil engraftment, and four cases of grade II+ GVHD. In group II, two patients had early graft failure (no take), and there were no cases of acute GVHD out of seven evaluable patients. One patient in group I developed chronic GVHD of the liver, and two patients (one in each group) had transient localised chronic GVHD. PCR of short tandem repeats was used to evaluate chimaeric status in 13 patients. Of 11 patients with initial neutrophil engraftment, only one had 100% donor haemopoiesis at all times. The remaining patients had either transient mixed chimaerism or persistence of recipient (< 20%) cells. We conclude that in vivo Campath-1G is associated with a high incidence of mixed chimaerism which tips the balance away from GVHD but towards graft rejection.

Published
1996

167. International women stage directors

Author

Lawler, M.

Subjects
International Women Stage Directors (Nonfiction work) -- Fliotsos, Anne -- Vierow, Wendy -- Book reviews, Books -- Book reviews, Library and information science, Literature/writing
Abstract

International women stage directors, ed. by Anne Fliotsos and Wendy Vierow. Illinois, 2013. 327p bibl index afp ISBN 9780252037818, 560.00 51-4178 PN 1590 2013-9259 CIP Unlike the authors' earlier American [...]

Published
2014

174. HOCl and Cl2 observations in marine air

Author

Lawler, M. J., primary, Sander, R., additional, Carpenter, L. J., additional, Lee, J. D., additional, von Glasow, R., additional, Sommariva, R., additional, and Saltzman, E. S., additional

Published
2011
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177. PBOX-15, a novel microtubule targeting agent, induces apoptosis, upregulates death receptors, and potentiates TRAIL-mediated apoptosis in multiple myeloma cells

Author

Maginn, E N, primary, Browne, P V, additional, Hayden, P, additional, Vandenberghe, E, additional, MacDonagh, B, additional, Evans, P, additional, Goodyer, M, additional, Tewari, P, additional, Campiani, G, additional, Butini, S, additional, Williams, D C, additional, Zisterer, D M, additional, Lawler, M P, additional, and McElligott, A M, additional

Published
2010
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179. Novel pyrrolo-1,5-benzoxazepine compounds display significant activity against resistant chronic myeloid leukaemia cells in vitro, in ex vivo patient samples and in vivo

Author

Bright, S A, primary, McElligott, A M, additional, O'Connell, J W, additional, O'Connor, L, additional, Carroll, P, additional, Campiani, G, additional, Deininger, M W, additional, Conneally, E, additional, Lawler, M, additional, Williams, D C, additional, and Zisterer, D M, additional

Published
2010
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181. Reactive Halogens in the Marine Boundary Layer (RHaMBLe): the tropical North Atlantic experiments

Author

Lee, J. D., primary, McFiggans, G., additional, Allan, J. D., additional, Baker, A. R., additional, Ball, S. M., additional, Benton, A. K., additional, Carpenter, L. J., additional, Commane, R., additional, Finley, B. D., additional, Evans, M., additional, Fuentes, E., additional, Furneaux, K., additional, Goddard, A., additional, Good, N., additional, Hamilton, J. F., additional, Heard, D. E., additional, Herrmann, H., additional, Hollingsworth, A., additional, Hopkins, J. R., additional, Ingham, T., additional, Irwin, M., additional, Jones, C. E., additional, Jones, R. L., additional, Keene, W. C., additional, Lawler, M. J., additional, Lehmann, S., additional, Lewis, A. C., additional, Long, M. S., additional, Mahajan, A., additional, Methven, J., additional, Moller, S. J., additional, Müller, K., additional, Müller, T., additional, Niedermeier, N., additional, O'Doherty, S., additional, Oetjen, H., additional, Plane, J. M. C., additional, Pszenny, A. A. P., additional, Read, K. A., additional, Saiz-Lopez, A., additional, Saltzman, E. S., additional, Sander, R., additional, von Glasow, R., additional, Whalley, L., additional, Wiedensohler, A., additional, and Young, D., additional

Published
2009
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184. The HIF-1α C1772T polymorphism may be associated with susceptibility to clinically localized prostate cancer but not with elevated expression of hypoxic biomarkers

Author

Foley, R, primary, Marignol, L, additional, Thomas, A.Z., additional, Cullen, I.M., additional, Perry, A.S, additional, Tewari, P., additional, O'Grady, A., additional, Kay, E, additional, Dunne, B., additional, Loftus, B., additional, Watson, R.W., additional, Fitzpatrick, J.M., additional, Woodson, K., additional, Lehman, T., additional, Hollywood, D., additional, Lynch, T.H., additional, and Lawler, M., additional

Published
2009
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185. Problems with the Baade-Wesselink method

Author

Bohm-Vitense, E, Garnavich, P, Lawler, M, Mena-Werth, J, and Morgan, S

Subjects
Astrophysics
Abstract

The discrepancy noted in radii obtained by the Baade-Wesselink method when different colors are used to determine the effective temperatures is explored. The discrepancy is found to be due to an inconsistency in the applied temperature-color calibrations. The assumption of the maximum likelihood method that beta (the effective temperature + 0.1 times the bolometric correction) is a linear function of the color is valid for the B-V and V-I colors, but not for the V-R colors. It is suggested that the errors introduced by the nonlinearity in the relation between beta and the V-R colors will produce radii which are too large. The radii derived from the V-B colors appear to be too small.

Published
1989
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190. Cyclosporin A and short-term methotrexate versus cyclosporin A as graft versus host disease prophylaxis in patients with severe aplastic anemia given allogeneic bone marrow transplantation from an HLA-identical sibling: results of a GITMO/EBMT randomized trial

Author

Locatelli, Franco, Bruno, B, Zecca, M, Van-Lint, M T, Mccann, S, Arcese, W, Dallorso, S, Di Bartolomeo, P, Fagioli, F, Locasciulli, A, Lawler, M, Bacigalupo, Andrea, Locatelli, F (ORCID:0000-0002-7976-3654), Bacigalupo, A (ORCID:0000-0002-9119-567X), Locatelli, Franco, Bruno, B, Zecca, M, Van-Lint, M T, Mccann, S, Arcese, W, Dallorso, S, Di Bartolomeo, P, Fagioli, F, Locasciulli, A, Lawler, M, Bacigalupo, Andrea, Locatelli, F (ORCID:0000-0002-7976-3654), and Bacigalupo, A (ORCID:0000-0002-9119-567X)

Abstract

A randomized trial was carried out comparing cyclosporin A (CsA) and short-term methotrexate (MTX) versus CsA alone for graft versus host disease (GVHD) prophylaxis in patients with severe aplastic anemia (SAA) undergoing allogeneic bone marrow transplantation (BMT) from a compatible sibling. Seventy-one patients (median age, 19 years; range, 4-46 years) were randomized to receive either CsA and MTX or CsA alone for the first 3 weeks after BMT. Subsequently, both groups received CsA orally, with gradual drug reduction until discontinuation 8 to 12 months after BMT. Patients randomized in both arms had comparable characteristics and received the same preparative regimen (ie, cyclophosphamide 200 mg/kg over 4 days). The median time for neutrophil engraftment was 17 days (range, 11-31 days) and 12 days (range, 4-45 days) for patients in the CsA/MTX group and the CsA alone group, respectively (P =.01). No significant difference was observed in the probability of either grade 2, grade 3, or grade 4 acute GVHD or chronic GVHD developing in the 2 groups. The Kaplan-Meier estimates of 1-year transplantation-related mortality rates for patients given either CsA/MTX or CsA alone were 3% and 15%, respectively (P =.07). With a median follow-up of 48 months from BMT, the 5-year survival probability is 94% for patients in the CsA/MTX group and 78% for those in the CsA alone group (P =. 05). These data indicate that the use of CsA with MTX is associated with improved survival in patients with SAA who receive transplants from compatible siblings. (Blood. 2000;96:1690-1697)

Published
2000

191. Variation in DNA repair genes XRCC3, XRCC4, XRCC5 and susceptibility to myeloma

Author

Hayden, P. J., primary, Tewari, P., additional, Morris, D. W., additional, Staines, A., additional, Crowley, D., additional, Nieters, A., additional, Becker, N., additional, de Sanjose, S., additional, Foretova, L., additional, Maynadie, M., additional, Cocco, P. L., additional, Boffetta, P., additional, Brennan, P., additional, Chanock, S. J., additional, Browne, P. V., additional, and Lawler, M., additional

Published
2007
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198. Hygroscopicity of nanoparticles produced from homogeneous nucleation in the CLOUD experiments.

Author

Kim, J., Ahlm, L., Yli-Juuti, T., Lawler, M., Keskinen, H., Tröstl, J., Schobesberger, S., Duplissy, J., Amorim, A., Bianchi, F., Donahue, N. M., Flagan, R. C., Hakala, J., Heinritzi, M., Jokinen, T., Kürten, A., Laaksonen, A., Lehtipalo, K., Miettinen, P., and Petäjä, T.

Abstract

Sulfuric acid, amines and oxidized organics have been found to be important compounds in the nucleation and initial growth of atmospheric particles. Because of the challenges involved in determining the chemical composition of objects with very small mass, however, the properties of the freshly nucleated particles and the detailed pathways of their formation processes are still not clear. In this study, we focus on a challenging size range, i.e. particles that have grown to diameters of 10 and 15nm following nucleation, and measure their water uptake. Water uptake constrains their chemical composition. We use a nanometer-hygroscopicity tandem differential mobility analyzer (nano-HTDMA) at subsaturated conditions (ca. 90% relative humidity at 293 K) to measure the hygroscopicity of particles during the seventh Cosmics Leaving OUtdoor Droplets (CLOUD7) experiments performed at CERN in 2012. In CLOUD7, the hygroscopicity of nucleated nanoparticles was measured in the presence of sulfuric acid, sulfuric acid-dimethylamine, and sulfuric acid-organics derived from α-pinene oxidation. The hygroscopicity parameter K decreased with increasing particle size indicating decreasing acidity of particles. No clear effect of the sulfuric acid monomer concentrations on the hygroscopicities of 10 nm particles produced from sulfuric acid and dimethylamine was observed, whereas the hygroscopicity of 15nm particles sharply decreased with decreasing sulfuric acid monomer concentrations. In particular, when the concentrations of sulfuric acid was 5.1 x 106 molecules cm-3 in the gas phase, and the dimethylamine mixing ratio was 11.8 ppt, the measured K of 15nm particles was 0.31 ±0.01 close to the value reported for dimethylamine sulfate (DMAS) (KDMAS28). Furthermore, the difference in K between sulfuric acid and sulfuric acid-dimethylamine experiments increased with increasing particle size. The K values of particles in the presence of sulfuric acid and organics were much smaller than those of particles in the presence of sulfuric acid and dimethylamine. This suggests that the organics produced from α-pinene ozonolysis play a significant role in particle growth already at 10 nm sizes. [ABSTRACT FROM AUTHOR]

Published
2015
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200. Marrow aplasia developing 13 years after HLA‐identical sibling allogeneic transplantation for chronic myeloid leukaemia: successful treatment with antithymocyte globulin and peripheral blood stem cell infusion from the original donor

Author

O'Donghaile, D, primary, Hayden, P. J., additional, McCarron, S. L., additional, Doyle, E. M., additional, Lawler, M., additional, Browne, P. V., additional, Conneally, E., additional, Vandenberghe, E., additional, and McCann, S. R., additional

Published
2006
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