Symmetric Instantons and Skyrme Fields

By explicit construction of the ADHM data, we prove the existence of a charge seven instanton with icosahedral symmetry. By computing the holonomy of this instanton we obtain a Skyrme field which approximates the minimal energy charge seven Skyrmion. We also present a one parameter family of tetrahedrally symmetric instantons whose holonomy gives a family of Skyrme fields which models a Skyrmion scattering process, where seven well-separated Skyrmions collide to form the icosahedrally symmetric Skyrmion.Comment: 22 pages plus 1 figure in GIF forma

An Overview of Rift Valley Fever Vaccine Development Strategies.

Rift Valley fever (RVF) is a mosquito-borne viral zoonosis that causes high fetal and neonatal mortality in ruminants and a mild to fatal hemorrhagic fever in humans. There are no licensed RVF vaccines for human use while for livestock, commercially available vaccines are all either live attenuated or inactivated and have undesirable characteristics. The live attenuated RVF vaccines are associated with teratogenicity and residual virulence in ruminants while the inactivated ones require multiple immunisations to induce and maintain protective immunity. Additionally, nearly all licensed RVF vaccines lack the differentiating infected from vaccinated animals (DIVA) property making them inappropriate for use in RVF nonendemic countries. To address these limitations, novel DIVA-compatible RVF vaccines with better safety and efficacy than the licensed ones are being developed, aided fundamentally by a better understanding of the molecular biology of the RVF virus and advancements in recombinant DNA technology. For some of these candidate RVF vaccines, sterilizing immunity has been demonstrated in the discovery/feasibility phase with minimal adverse effects. This review highlights the progress made to date in RVF vaccine research and development and discusses the outstanding research gaps

A Multi-Component Prime-Boost Vaccination Regimen with a Consensus MOMP Antigen Enhances Chlamydia trachomatis Clearance

The Supplementary Material for this article can be found online at http://journal.frontiersin.org/article/10.3389/fimmu.2016.00162BACKGROUND: A vaccine for Chlamydia trachomatis is of urgent medical need. We explored bioinformatic approaches to generate an immunogen against C. trachomatis that would induce cross-serovar T-cell responses as (i) CD4(+) T cells have been shown in animal models and human studies to be important in chlamydial protection and (ii) antibody responses may be restrictive and serovar specific. METHODS: A consensus antigen based on over 1,500 major outer membrane protein (MOMP) sequences provided high epitope coverage against the most prevalent C. trachomatis strains in silico. Having designed the T-cell immunogen, we assessed it for immunogenicity in prime-boost regimens. This consensus MOMP transgene was delivered using plasmid DNA, Human Adenovirus 5 (HuAd5) or modified vaccinia Ankara (MVA) vectors with or without MF59(®) adjuvanted recombinant MOMP protein. RESULTS: Different regimens induced distinct immune profiles. The DNA-HuAd5-MVA-Protein vaccine regimen induced a cellular response with a Th1-biased serum antibody response, alongside high serum and vaginal MOMP-specific antibodies. This regimen significantly enhanced clearance against intravaginal C. trachomatis serovar D infection in both BALB/c and B6C3F1 mouse strains. This enhanced clearance was shown to be CD4(+) T-cell dependent. Future studies will need to confirm the specificity and precise mechanisms of protection. CONCLUSION: A C. trachomatis vaccine needs to induce a robust cellular response with broad cross-serovar coverage and a heterologous prime-boost regimen may be an approach to achieve this.AB was funded by the Wellcome Trust. RS was supported by the European Community’s European 7th Framework Program ADITEC (HEALTH-F4-2011-18 280873).info:eu-repo/semantics/publishedVersio

Log-periodic route to fractal functions

Log-periodic oscillations have been found to decorate the usual power law behavior found to describe the approach to a critical point, when the continuous scale-invariance symmetry is partially broken into a discrete-scale invariance (DSI) symmetry. We classify the `Weierstrass-type'' solutions of the renormalization group equation F(x)= g(x)+(1/m)F(g x) into two classes characterized by the amplitudes A(n) of the power law series expansion. These two classes are separated by a novel ``critical'' point. Growth processes (DLA), rupture, earthquake and financial crashes seem to be characterized by oscillatory or bounded regular microscopic functions g(x) that lead to a slow power law decay of A(n), giving strong log-periodic amplitudes. In contrast, the regular function g(x) of statistical physics models with ``ferromagnetic''-type interactions at equibrium involves unbound logarithms of polynomials of the control variable that lead to a fast exponential decay of A(n) giving weak log-periodic amplitudes and smoothed observables. These two classes of behavior can be traced back to the existence or abscence of ``antiferromagnetic'' or ``dipolar''-type interactions which, when present, make the Green functions non-monotonous oscillatory and favor spatial modulated patterns.Comment: Latex document of 29 pages + 20 ps figures, addition of a new demonstration of the source of strong log-periodicity and of a justification of the general offered classification, update of reference lis

Mucosal Application of gp140 Encoding DNA Polyplexes to Different Tissues Results in Altered Immunological Outcomes in Mice

Increasing evidence suggests that mucosally targeted vaccines will enhance local humoral and cellular responses whilst still eliciting systemic immunity. We therefore investigated the capacity of nasal, sublingual or vaginal delivery of DNA-PEI polyplexes to prime immune responses prior to mucosal protein boost vaccination. Using a plasmid expressing the model antigen HIV CN54gp140 we show that each of these mucosal surfaces were permissive for DNA priming and production of antigen-specific antibody responses. The elicitation of systemic immune responses using nasally delivered polyplexed DNA followed by recombinant protein boost vaccination was equivalent to a systemic prime-boost regimen, but the mucosally applied modality had the advantage in that significant levels of antigen-specific IgA were detected in vaginal mucosal secretions. Moreover, mucosal vaccination elicited both local and systemic antigen-specific IgG(+) and IgA(+) antibody secreting cells. Finally, using an Influenza challenge model we found that a nasal or sublingual, but not vaginal, DNA prime/protein boost regimen protected against infectious challenge. These data demonstrate that mucosally applied plasmid DNA complexed to PEI followed by a mucosal protein boost generates sufficient antigen-specific humoral antibody production to protect from mucosal viral challenge

Increasing human monoclonal antibody cloning efficiency with a whole-cell modified immunoglobulin-capture assay (mICA)

Expression cloning of fully human monoclonal antibodies (hmAbs) is seeing powerful utility in the field of vaccinology, especially for elucidating vaccine-induced B-cell responses and novel vaccine candidate antigen discovery. Precision of the hmAb cloning process relies on efficient isolation of hmAb-producing plasmablasts of interest. Previously, a novel immunoglobulin-capture assay (ICA) was developed, using single protein vaccine antigens, to enhance the pathogen-specific hmAb cloning output. Here, we report a novel modification of this single-antigen ICA using formalin-treated, fluorescently stained whole cell suspensions of the human bacterial invasive pathogens, Streptococcus pneumoniae and Neisseria meningitidis. Sequestration of IgG secreted by individual vaccine antigen-specific plasmablasts was achieved by the formation of an anti-CD45-streptavidin and biotin anti-IgG scaffold. Suspensions containing heterologous pneumococcal and meningococcal strains were then used to enrich for polysaccharide- and protein antigen-specific plasmablasts, respectively, during single cell sorting. Following application of the modified whole-cell ICA (mICA), ~61% (19/31) of anti-pneumococcal polysaccharide hmAbs were cloned compared to 14% (8/59) obtained using standard (non-mICA) methods – representing a ~4.4-fold increase in hmAb cloning precision. A more modest ~1.7-fold difference was obtained for anti-meningococcal vaccine hmAb cloning; ~88% of hmAbs cloned via mICA versus ~53% cloned via the standard method were specific for a meningococcal surface protein. VDJ sequencing revealed that cloned hmAbs reflected an anamnestic response to both pneumococcal and meningococcal vaccines; diversification within hmAb clones occurred by positive selection for replacement mutations. Thus, we have shown successful utilization of whole bacterial cells in the ICA protocol enabling isolation of hmAbs targeting multiple disparate epitopes, thereby increasing the power of approaches such as reverse vaccinology 2.0 (RV 2.0) for bacterial vaccine antigen discovery

Evidence for Reionization at z ~ 6: Detection of a Gunn-Peterson Trough in a z=6.28 Quasar

We present moderate resolution Keck spectroscopy of quasars at z=5.82, 5.99 and 6.28, discovered by the Sloan Digital Sky Survey (SDSS). We find that the Ly Alpha absorption in the spectra of these quasars evolves strongly with redshift. To z~5.7, the Ly Alpha absorption evolves as expected from an extrapolation from lower redshifts. However, in the highest redshift object, SDSSp J103027.10+052455.0 (z=6.28), the average transmitted flux is 0.0038+-0.0026 times that of the continuum level over 8450 A < lambda < 8710 A (5.95<z(abs)<6.16), consistent with zero flux. Thus the flux level drops by a factor of >150, and is consistent with zero flux in the Ly Alpha forest region immediately blueward of the Ly Alpha emission line, compared with a drop by a factor of ~10 at z(abs)~5.3. A similar break is seen at Ly Beta; because of the decreased oscillator strength of this transition, this allows us to put a considerably stronger limit, tau(eff) > 20, on the optical depth to Ly Alpha absorption at z=6. This is a clear detection of a complete Gunn-Peterson trough, caused by neutral hydrogen in the intergalactic medium. Even a small neutral hydrogen fraction in the intergalactic medium would result in an undetectable flux in the Ly Alpha forest region. Therefore, the existence of the Gunn-Peterson trough by itself does not indicate that the quasar is observed prior to the reionization epoch. However, the fast evolution of the mean absorption in these high-redshift quasars suggests that the mean ionizing background along the line of sight to this quasar has declined significantly from z~5 to 6, and the universe is approaching the reionization epoch at z~6.Comment: Revised version (2001 Sep 4) accepted by the Astronomical Journal (minor changes

Developing general cultural awareness in a monocultural English as a foreign language context in a Mexican university: a wiki-based critical incident approach

© 2013 Association for Language Learning. This article explores what the ‘intercultural turn’ might mean in the case of teaching English to speakers of other languages (TESOL). The discussion is contextualised in what has been termed the ‘expanding circle’ of English and focuses on an English as a foreign language (EFL) class in a Mexican university, a context where the full implications of a shift from EFL to English as a lingua franca (ELF) have yet to be addressed. We consider how the intercultural turn might be understood in this Mexican context and then present the rationale for, and design of, a technology-based (wiki) extra-curricular pilot project which adopted less of an EFL/cultural and more of an ELF/intercultural approach. We evaluate the evidence from this small-scale project in terms of students\u27 developing general cultural awareness and suggest that this type of project, an example of the intercultural turn, might be more widely applicable in similar ‘expanding circle’ EFL contexts