Publications
134 results found
Veazey RS, Siddiqui A, Klein K, et al., 2015, Evaluation of mucosal adjuvants and immunization routes for the induction of systemic and mucosal humoral immune responses in macaques, Human Vaccines & Immunotherapeutics, Vol: 11, Pages: 2913-2922, ISSN: 2164-5515
Delivering vaccine antigens to mucosal surfaces is potentially very attractive, especially as protection from mucosal infections may be mediated by local immune responses. However, to date mucosal immunization has had limited successes, with issues of both safety and poor immunogenicity. One approach to improve immunogenicity is to develop adjuvants that are effective and safe at mucosal surfaces. Differences in immune responses between mice and men have overstated the value of some experimental adjuvants which have subsequently performed poorly in the clinic. Due to their closer similarity, non-human primates can provide a more accurate picture of adjuvant performance. In this study we immunised rhesus macaques (Macaca mulatta) using a unique matrix experimental design that maximised the number of adjuvants screened while reducing the animal usage. Macaques were immunised by the intranasal, sublingual and intrarectal routes with the model protein antigens keyhole limpet haemocyanin (KLH), β-galactosidase (β-Gal) and ovalbumin (OVA) in combination with the experimental adjuvants Poly(I:C), Pam3CSK4, chitosan, Thymic Stromal Lymphopoietin (TSLP), MPLA and R848 (Resiquimod). Of the routes used, only intranasal immunization with KLH and R848 induced a detectable antibody response. When compared to intramuscular immunization, intranasal administration gave slightly lower levels of antigen specific antibody in the plasma, but enhanced local responses. Following intranasal delivery of R848, we observed a mildly inflammatory response, but no difference to the control. From this we conclude that R848 is able to boost antibody responses to mucosally delivered antigen, without causing excess local inflammation.
Badamchi-Zadeh A, McKay PF, Holland MJ, et al., 2015, Intramuscular Immunisation with Chlamydial Proteins Induces <i>Chlamydia trachomatis</i> Specific Ocular Antibodies, PLOS ONE, Vol: 10, ISSN: 1932-6203
- Author Web Link
- Open Access Link
- Cite
- Citations: 18
Siggins MK, Gill SK, Langford PR, et al., 2015, PHiD-CV induces anti-Protein D antibodies but does not augment pulmonary clearance of nontypeable Haemophilus influenzae in mice, Vaccine, Vol: 33, Pages: 4954-4961, ISSN: 1873-2518
BackgroundA recently-licensed 10-valent pneumococcal conjugate vaccine (PHiD-CV; Synflorix, GSK) uses Protein D from Haemophilus influenzae as a carrier protein. PHiD-CV therefore has the potential to provide additional protection against nontypeable H. influenzae (NTHi). NTHi frequently causes respiratory tract infections and is associated with significant morbidity and mortality worldwide and there is currently no vaccine.MethodsWe developed mouse models of NTHi infection and influenza/NTHi superinfection. Mice were immunized with PHiD-CV, heat-killed NTHi, or a 13-valent pneumococcal conjugate vaccine that did not contain Protein D (PCV13; Prevenar, Pfizer) and then infected intranasally with NTHi.ResultsInfection with NTHi resulted in weight loss, inflammation and airway neutrophilia. In a superinfection model, prior infection with pandemic H1N1 influenza virus (strain A/England/195/2009) augmented NTHi infection severity, even with a lower bacterial challenge dose. Immunization with PHiD-CV produced high levels of antibodies that were specific against Protein D, but not heat-killed NTHi. Immunization with PHiD-CV led to a slight reduction in bacterial load, but no change in disease outcome.ConclusionsPHiD-CV induced high levels of Protein D-specific antibodies, but did not augment pulmonary clearance of NTHi. We found no evidence to suggest that PHiD-CV will offer added benefit by preventing NTHi lung infection.
Kinnear E, Caproni LJ, Tregoning JS, 2015, A Comparison of Red Fluorescent Proteins to Model DNA Vaccine Expression by Whole Animal In Vivo Imaging, PLOS One, Vol: 10, ISSN: 1932-6203
DNA vaccines can be manufactured cheaply, easily and rapidly and have performed well inpre-clinical animal studies. However, clinical trials have so far been disappointing, failing toevoke a strong immune response, possibly due to poor antigen expression. To improveantigen expression, improved technology to monitor DNA vaccine transfection efficiency isrequired. In the current study, we compared plasmid encoded tdTomato, mCherry,Katushka, tdKatushka2 and luciferase as reporter proteins for whole animal in vivo imaging.The intramuscular, subcutaneous and tattooing routes were compared and electroporationwas used to enhance expression. We observed that overall, fluorescent proteins were not agood tool to assess expression from DNA plasmids, with a highly heterogeneous responsebetween animals. Of the proteins used, intramuscular delivery of DNA encoding either tdTomatoor luciferase gave the clearest signal, with some Katushka and tdKatushka2 signalobserved. Subcutaneous delivery was weakly visible and nothing was observed followingDNA tattooing. DNA encoding haemagglutinin was used to determine whether immuneresponses mirrored visible expression levels. A protective immune response against H1N1influenza was induced by all routes, even after a single dose of DNA, though qualitative differenceswere observed, with tattooing leading to high antibody responses and subcutaneousDNA leading to high CD8 responses. We conclude that of the reporter proteins used,expression from DNA plasmids can best be assessed using tdTomato or luciferase. But, thedisconnect between visible expression level and immunogenicity suggests that in vivowhole animal imaging of fluorescent proteins has limited utility for predicting DNA vaccineefficacy.
Russell RF, McDonald JU, Ivanova M, et al., 2015, Partialattenuation of respiratory syncytial virus with a deletion of a small hydrophobic gene Is associated with elevated interleukin-1β responses, Journal of Virology, Vol: 89, Pages: 8974-8981, ISSN: 1098-5514
The small hydrophobic (SH) gene of respiratory syncytial virus (RSV), a major cause of infant hospitalization, encodes a viroporin of unknown function. SH gene knockout virus (RSV ΔSH) is partially attenuated in vivo, but not in vitro, suggesting that the SH protein may have an immunomodulatory role. RSV ΔSH has been tested as a live attenuated vaccine in humans and cattle, and here we demonstrate that it protected against viral rechallenge in mice. We compared the immune response to infection with RSV wild type and RSV ΔSH in vivo using BALB/c mice and in vitro using epithelial cells, neutrophils, and macrophages. Strikingly, the interleukin-1β (IL-1β) response to RSV ΔSH infection was greater than to wild-type RSV, in spite of a decreased viral load, and when IL-1β was blocked in vivo, the viral load returned to wild-type levels. A significantly greater IL-1β response to RSV ΔSH was also detected in vitro, with higher-magnitude responses in neutrophils and macrophages than in epithelial cells. Depleting macrophages (with clodronate liposome) and neutrophils (with anti-Ly6G/1A8) demonstrated the contribution of these cells to the IL-1β response in vivo, the first demonstration of neutrophilic IL-1β production in response to viral lung infection. In this study, we describe an increased IL-1β response to RSV ΔSH, which may explain the attenuation in vivo and supports targeting the SH gene in live attenuated vaccines.
Tregoning JS, Kinnear E, 2015, Using Plasmids as DNA Vaccines for Infectious Diseases, Plasmids: Biology and Impact in Biotechnology and Discovery, Pages: 651-668, ISBN: 9781555818975
- Cite
- Citations: 6
Mastelic Gavillet B, Eberhardt CS, Auderset F, et al., 2015, MF59 Mediates Its B Cell Adjuvanticity by Promoting T Follicular Helper Cells and Thus Germinal Center Responses in Adult and Early Life., Journal of Immunology, Vol: 194, Pages: 4836-4845, ISSN: 0022-1767
The early life influenza disease burden calls for more effective vaccines to protect this vulnerable population. Influenza vaccines including the MF59 oil-in-water adjuvant induce higher, broader, and more persistent Ab responses in adults and particularly in young, through yet undefined mechanisms. In this study, we show that MF59 enhances adult murine IgG responses to influenza hemagglutinin (HA) by promoting a potent T follicular helper cells (TFH) response, which directly controls the magnitude of the germinal center (GC) B cell response. Remarkably, this enhancement of TFH and GC B cells is already fully functional in 3-wk-old infant mice, which were fully protected by HA/MF59 but not HA/PBS immunization against intranasal challenge with the homologous H1N1 (A/California/7/2009) strain. In 1-wk-old neonatal mice, MF59 recruits and activates APCs, efficiently induces CD4(+) effector T cells and primes for enhanced infant responses but induces few fully functional TFH cells, which are mostly follicular regulatory T cells, and poor GC and anti-HA responses. The B cell adjuvanticity of MF59 appears to be mediated by the potent induction of TFH cells which directly controls GC responses both in adult and early life, calling for studies assessing its capacity to enhance the efficacy of influenza immunization in young infants.
Tregoning JS, Kinnear E, 2014, Using Plasmids as DNA Vaccines for Infectious Diseases., Plasmids: Biology and Impact in Biotechnology and Discovery, Publisher: ASMscience, ISBN: 9781555818975
DNA plasmids can be used to induce a protective (or therapeutic) immune response by delivering genes encoding vaccine antigens. That naked DNA (without the refinement of coat proteins or host evasion systems) can cross from outside the cell into the nucleus and be expressed is particularly remarkable given the sophistication of the immune system in preventing infection by pathogens. As a result of the ease, low cost, and speed of custom gene synthesis, DNA vaccines dangle a tantalizing prospect of the next wave of vaccine technology, promising individual designer vaccines for cancer or mass vaccines with a rapid response time to emerging pandemics. There is considerable enthusiasm for the use of DNA vaccination as an approach, but this enthusiasm should be tempered by the successive failures in clinical trials to induce a potent immune response. The technology is evolving with the development of improved delivery systems that increase expression levels, particularly electroporation and the incorporation of genetically encoded adjuvants. This review will introduce some key concepts in the use of DNA plasmids as vaccines, including how the DNA enters the cell and is expressed, how it induces an immune response, and a summary of clinical trials with DNA vaccines. The review also explores the advances being made in vector design, delivery, formulation, and adjuvants to try to realize the promise of this technology for new vaccines. If the immunogenicity and expression barriers can be cracked, then DNA vaccines may offer a step change in mass vaccination.
Walters AA, Kinnear E, Shattock RJ, et al., 2014, Comparative analysis of enzymatically produced novel linear DNA constructs with plasmids for use as DNA vaccines, Gene Therapy, Vol: 21, Pages: 645-652, ISSN: 1476-5462
Harker JA, Yamaguchi Y, Culley FJ, et al., 2014, Delayed sequelae of neonatal RSV infection are dependent on cells of the innate immune system, Journal of Virology, ISSN: 0022-538X
Infection with respiratory syncytial virus (RSV) in neonatal mice leads to exacerbated disease if mice are re-infected with the same virus as adults. Both T cells and host MHC genotype contribute to this phenomenon, but the part played by innate immunity has not been defined. Since macrophages and natural killer (NK) cells play key roles in regulating inflammation during RSV infection of adult mice, we studied the role of these cells in exacerbated inflammation following neonatal RSV sensitization/adult re-infection. Compared to those undergoing primary adult infection, neonatally sensitized mice showed enhanced airway fluid levels of interleukin-6 (IL-6), interferon alpha (IFNα), CXCL1 (KC) and tumor necrosis factor alpha (TNFα) at 12-24h, and IL-4, IL-5, IFNγ and CCL11 (eotaxin) at day 4 after re-infection. Weight loss during re-infection was accompanied by an initial influx of NK cells and granulocytes into the airways and lungs, followed by T cells. NK depletion during re-infection attenuated weight loss, but did not alter T cell responses. Depleting alveolar macrophages with inhaled clodronate liposomes reduced both NK and T cell numbers and attenuated weight loss. These findings indicate a hitherto unappreciated role for the innate immune response in governing the pathogenic recall responses to RSV infection.
Everitt AR, Clare S, McDonald JU, et al., 2013, Defining the Range of Pathogens Susceptible to Ifitm3 Restriction Using a Knockout Mouse Model, PLOS ONE, Vol: 8, ISSN: 1932-6203
- Author Web Link
- Open Access Link
- Cite
- Citations: 54
Tregoning JS, Buffa V, Oszmiana A, et al., 2013, A "Prime-Pull" Vaccine Strategy Has a Modest Effect on Local and Systemic Antibody Responses to HIV gp140 in Mice, PLOS One, Vol: 8, ISSN: 1932-6203
One potential strategy for the prevention of HIV infection is to induce virus specific mucosal antibody that can act as animmune barrier to prevent transmission. The mucosal application of chemokines after immunisation, termed ‘‘prime-pull’’,has been shown to recruit T cells to mucosal sites. We wished to determine whether this strategy could be used to increaseB cells and antibody in the vaginal mucosa following immunisation with an HIV antigen. BALB/c mice were immunisedintranasally with trimeric gp140 prior to vaginal application of the chemokine CCL28 or the synthetic TLR4 ligand MPLA,without antigen six days later. There was no increase in vaginal IgA, IgG or B cells following the application of CCL28,however vaginal application of MPLA led to a significant boost in antigen specific vaginal IgA. Follow up studies toinvestigate the effect of the timing of the ‘‘pull’’ stimulation demonstrated that when given 14 days after the initialimmunisation MPLA significantly increased systemic antibody responses. We speculate that this may be due to residualinflammation prior to re-immunisation. Overall we conclude that in contrast to the previously observed effect on T cells, theuse of ‘‘prime-pull’’ has only a modest effect on B cells and antibody.
Garnett JP, Baker EH, Naik S, et al., 2013, Metformin reduces airway glucose permeability and hyperglycaemia-induced Staphylococcus aureus load independently of effects on blood glucose, Thorax, Vol: 68, Pages: 835-845, ISSN: 0040-6376
Background Diabetes is a risk factor for respiratoryinfection, and hyperglycaemia is associated withincreased glucose in airway surface liquid and risk ofStaphylococcus aureus infection.Objectives To investigate whether elevation ofbasolateral/blood glucose concentration promotes airwayStaphylococcus aureus growth and whether pretreatmentwith the antidiabetic drug metformin affects thisrelationship.Methods Human airway epithelial cells grown atair–liquid interface (±18 h pre-treatment, 30 μM–1 mMmetformin) were inoculated with 5×105 colony-formingunits (CFU)/cm2 S aureus 8325-4 or JE2 orPseudomonas aeruginosa PA01 on the apical surfaceand incubated for 7 h. Wild-type C57BL/6 or db/db(leptin receptor-deficient) mice, 6–10 weeks old, weretreated with intraperitoneal phosphate-buffered saline or40 mg/kg metformin for 2 days before intranasalinoculation with 1×107 CFU S aureus. Mice were culled24 h after infection and bronchoalveolar lavage fluidcollected.Results Apical S aureus growth increased withbasolateral glucose concentration in an in vitro airwayepithelia–bacteria co-culture model. S aureus reducedtransepithelial electrical resistance (RT) and increasedparacellular glucose flux. Metformin inhibited theglucose-induced growth of S aureus, increased RT anddecreased glucose flux. Diabetic (db/db) mice infectedwith S aureus exhibited a higher bacterial load in theirairways than control mice after 2 days and metformintreatment reversed this effect. Metformin did notdecrease blood glucose but reduced paracellular fluxacross ex vivo murine tracheas.Conclusions Hyperglycaemia promotes respiratoryS aureus infection, and metformin modifies glucose fluxacross the airway epithelium to limit hyperglycaemiainducedbacterial growth. Metformin might, therefore, beof additional benefit in the prevention and treatment ofrespiratory infection.
Mann JFS, Mckay PF, Arokiasamy S, et al., 2013, Mucosal Application of gp140 Encoding DNA Polyplexes to Different Tissues Results in Altered Immunological Outcomes in Mice, PLOS ONE, Vol: 8, ISSN: 1932-6203
- Author Web Link
- Open Access Link
- Cite
- Citations: 14
Tregoning JS, Wang BL, McDonald JU, et al., 2013, Neonatal antibody responses are attenuated by interferon-γ produced by NK and T cells during RSV infection, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 110, Pages: 5576-5581, ISSN: 0027-8424
- Author Web Link
- Open Access Link
- Cite
- Citations: 32
Garnett JP, Baker EH, Tregoning JS, et al., 2013, Metformin Inhibits Hyperglycemia-Induced Airway Bacterial Growth And Is Associated With Reduced Transepithelial Glucose Permeability, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 187, ISSN: 1073-449X
Yamaguchi Y, Harker JA, Wang B, et al., 2012, Preexposure to CpG Protects against the Delayed Effects of Neonatal Respiratory Syncytial Virus Infection, JOURNAL OF VIROLOGY, Vol: 86, Pages: 10456-10461, ISSN: 0022-538X
- Author Web Link
- Open Access Link
- Cite
- Citations: 27
Arias MA, Van Roey GA, Tregoning JS, et al., 2012, Glucopyranosyl Lipid Adjuvant (GLA), a Synthetic TLR4 Agonist, Promotes Potent Systemic and Mucosal Responses to Intranasal Immunization with HIVgp140, PLOS One, Vol: 7, ISSN: 1932-6203
Successful vaccine development against HIV will likely require the induction of strong, long-lasting humoral and cellularimmune responses in both the systemic and mucosal compartments. Based on the known immunological linkage betweenthe upper-respiratory and urogenital tracts, we explored the potential of nasal adjuvants to boost immunization for theinduction of vaginal and systemic immune responses to gp140. Mice were immunized intranasally with HIV gp140 togetherwith micellar and emulsion formulations of a synthetic TLR4 agonist, Glucopyranosyl Lipid Adjuvant (GLA) and responseswere compared to R848, a TLR7/8 agonist, or chitosan, a non TLR adjuvant. GLA and chitosan but not R848 greatlyenhanced serum immunoglobulin levels when compared to antigen alone. Both GLA and chitosan induced high IgG andIgA titers in nasal and vaginal lavage and feces. The high IgA and IgG titers in vaginal lavage were associated with highnumbers of gp140-specific antibody secreting cells in the genital tract. Whilst both GLA and chitosan induced T cellresponses to immunization, GLA induced a stronger Th17 response and chitosan induced a more Th2 skewed response. Ourresults show that GLA is a highly potent intranasal adjuvant greatly enhancing humoral and cellular immune responses,both systemically and mucosally.
Van Roey GA, Arias MA, Tregoning JS, et al., 2012, Thymic stromal lymphopoietin (TSLP) acts as a potent mucosal adjuvant for HIV-1 gp140 vaccination in mice, European Journal of Immunology, Vol: 42, Pages: 353-363, ISSN: 1521-4141
The development of a successful vaccine against HIV is likely to require the induction of strong and long-lasting humoral immune responses at the mucosal portal of virus entry. Hence, the design of a vaccine strategy able to induce mucosal antibodies and in particular specific IgA, may be crucial to providing immune protection. Nasal immunisation is known to induce specific IgG and IgA responses in the cervicovaginal mucosa; however, there is an urgent need for the development of safe, effective and accessible mucosal adjuvants for nasal application in humans. To reduce the potential for adverse events associated with some nasal adjuvants, we have assessed whether the B-cell-activating cytokines APRIL, BAFF and TSLP enhance humoral immune responses to HIV-1 gp140. Following intranasal immunisation, TSLP but not APRIL or BAFF induced strong humoral responses both in serum and mucosa. The adjuvant effect of TSLP on humoral responses was similar to that of cholera toxin (CT). The use of TSLP as an adjuvant skewed both the cellular and humoral immune responses towards Th2 cells. This is the first time that TSLP has been demonstrated to have a positive effect as a mucosal adjuvant, and specifically to promote mucosal and systemic responses to HIV gp140.
Van Roey G, Arias M, Tregoning J, et al., 2011, TSLP, a potential new mucosal adjuvant for intranasal immunisation with HIV-1 gp140, AIDS Vaccine Conference, Bangkok, Thailand
Donnelly L, Curran RM, Tregoning JS, et al., 2011, Intravaginal immunization using the recombinant HIV-1 clade-C trimeric envelope glycoprotein CN54gp140 formulated within lyophilized solid dosage forms, Vaccine, Vol: 29, Pages: 4512-4520, ISSN: 1873-2518
Vaccine-mediated prevention of primary HIV-1 infection at the heterosexual mucosal portal of entry may be facilitated by highly optimised formulations or drug delivery devices for intravaginal (i.vag) immunization. Previously we described hydroxyethylcellulose (HEC)-based rheologically structured gel vehicles (RSVs) for vaginal immunization of an HIV-1 vaccine candidate, a soluble recombinant trimeric HIV-1 clade-C envelope glycoprotein designated CN54gp140. Here we investigated the efficacy of lyophilized solid dosage formulations (LSDFs) for prolonging antigen stability and as i.vag delivery modalities. LSDFs were designed and developed that upon i.vag administration they would reconstitute with the imbibing of vaginal fluid to mucoadhesive, site-retentive semi-solids. Mice were immunized with lyophilized equivalents of (i) RSVs, (ii) modified versions of the RSVs more suited to lyophilization (sodium carboxymethyl cellulose (NaCMC)-based gels) and (iii) Carbopol® gel, all containing CN54gp140. NaCMC-based LSDFs provided significantly enhanced antigen stability compared to aqueous-based RSVs. Rheological analysis indicated the NaCMC-based LSDFs would offer enhanced vaginal retention in woman compared to more conventional vaginal gel formulations. All LSDFs were well tolerated in the mouse model. Following i.vag administration, all LSDFs boosted systemic CN54gp140-specific antibody responses in sub-cutaneously primed mice. Induction of CN54gp140-specific antibody responses in the female genital tract was evident. Of all the LSDFs the fastest releasing which was lyophilized Carbopol® gel elicited immune responses comparable to buffer instillation of antigen suggesting that rather than slower sustained release, initial high burst release from the LSDFs may suffice. The boosting of specific immune responses upon i.vag administration indicates that LSDFs are viable mucosal vaccine delivery modalities promoting antigen stability and facilitating intimate exposur
Tregoning JS, Yamaguchi Y, Wang B, et al., 2010, Genetic Susceptibility to the Delayed Sequelae of Neonatal Respiratory Syncytial Virus Infection Is MHC Dependent, JOURNAL OF IMMUNOLOGY, Vol: 185, Pages: 5384-5391, ISSN: 0022-1767
- Author Web Link
- Open Access Link
- Cite
- Citations: 33
Lee DCP, Harker JAE, Tregoning JS, et al., 2010, CD25<SUP>+</SUP> Natural Regulatory T Cells Are Critical in Limiting Innate and Adaptive Immunity and Resolving Disease following Respiratory Syncytial Virus Infection, JOURNAL OF VIROLOGY, Vol: 84, Pages: 8790-8798, ISSN: 0022-538X
- Author Web Link
- Open Access Link
- Cite
- Citations: 115
Harker JA, Lee DCP, Yamaguchi Y, et al., 2010, Delivery of Cytokines by Recombinant Virus in Early Life Alters the Immune Response to Adult Lung Infection, JOURNAL OF VIROLOGY, Vol: 84, Pages: 5294-5302, ISSN: 0022-538X
- Author Web Link
- Open Access Link
- Cite
- Citations: 24
Harker JA, Godlee A, Wahlsten JL, et al., 2010, Interleukin 18 Coexpression during Respiratory Syncytial Virus Infection Results in Enhanced Disease Mediated by Natural Killer Cells, JOURNAL OF VIROLOGY, Vol: 84, Pages: 4073-4082, ISSN: 0022-538X
- Author Web Link
- Cite
- Citations: 44
Tregoning JS, Pribul PK, Pennycook AMJ, et al., 2010, The Chemokine MIP1α/CCL3 Determines Pathology in Primary RSV Infection by Regulating the Balance of T Cell Populations in the Murine Lung, PLOS ONE, Vol: 5, ISSN: 1932-6203
- Author Web Link
- Open Access Link
- Cite
- Citations: 38
Tregoning JS, Schwarze J, 2010, Respiratory Viral Infections in Infants: Causes, Clinical Symptoms, Virology, and Immunology, CLINICAL MICROBIOLOGY REVIEWS, Vol: 23, Pages: 74-+, ISSN: 0893-8512
- Author Web Link
- Cite
- Citations: 481
Buffa V, Klein K, Tregoning J, et al., 2009, P02-03. Screening of potential adjuvants for induction of pro-IgA factors, Retrovirology, Vol: 6
Buffa V, Klein K, Tregoning J, et al., 2009, Screening of potential adjuvants for induction of pro-IgA factors
Pribul PK, Harker J, Wang B, et al., 2008, Alveolar macrophages are a major determinant of early responses to viral lung infection but do not influence subsequent disease development, JOURNAL OF VIROLOGY, Vol: 82, Pages: 4441-4448, ISSN: 0022-538X
- Author Web Link
- Cite
- Citations: 157
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.