Recent developments in Quantum Monte-Carlo simulations with applications for cold gases

This is a review of recent developments in Monte Carlo methods in the field of ultra cold gases. For bosonic atoms in an optical lattice we discuss path integral Monte Carlo simulations with worm updates and show the excellent agreement with cold atom experiments. We also review recent progress in simulating bosonic systems with long-range interactions, disordered bosons, mixtures of bosons, and spinful bosonic systems. For repulsive fermionic systems determinantal methods at half filling are sign free, but in general no sign-free method exists. We review the developments in diagrammatic Monte Carlo for the Fermi polaron problem and the Hubbard model, and show the connection with dynamical mean-field theory. We end the review with diffusion Monte Carlo for the Stoner problem in cold gases.Comment: 68 pages, 22 figures, review article; replaced with published versio

Induction of changes in antigen expression at the surface membrane of adult male Schistosoma mansoni

Summary available: p.xxii

Induction of protective immune responses against schistosomiasis using functionally active cysteine peptidases

Each year schistosomiasis afflicts up to 600 million people in 74 tropical and sub-tropical countries, predominantly in the developing world. Yet we depend on a single drug, praziquantel, for its treatment and control. There is no vaccine available but one is urgently needed especially since praziquantel-resistant parasites are likely to emerge at some time in the future. The disease is caused by several worm species of the genus Schistosoma. These express several classes of papain-like cysteine peptidases, cathepsins B and L, in various tissues but particularly in their gastrodermis where they employ them as digestive enzymes. We have shown that sub-cutaneous injection of recombinant and functionally active Schistosoma mansoni cathepsin B1 (SmCB1), or a cathepsin L from a related parasite Fasciola hepatica (FhCL1), elicits highly significant protection (up to 73%) against an experimental challenge worm infection in murine models of schistosomiasis. The immune modulating properties of this subcutaneous injection can boost protection levels (up to 83%) when combined with other S. mansoni vaccine candidates, glyceraldehyde 3-phosphate dehydrogenase (SG3PDH) and peroxiredoxin (PRX-MAP). Here, we discuss these data in the context of the parasite's biology and development, and provide putative mechanism by which the native-like cysteine peptidase induce protective immune responses. © 2014 El Ridi, Tallima, Dalton and Donnelly

Molecular and immunological characterisation of two vaccine dominant antigens of Schistosoma mansoni.

Exposure to radiation attenuated cercariae of Schistosoma mansoni induces immunologically mediated protection against a challenge infection. One approach towards the selection of putative vaccine candidate molecules has therefore been the identification of ’vaccine dominant' antigens. Such molecules can be defined as those which are recognised by sera from animals vaccinated with irradiated parasites but not by sera raised in non-immune animals harbouring a single sex infection. This thesis describes the immunological and molecular characterisation of a 16 kDa vaccine dominant schistosomula surface antigen of S.mansoni and a 15 kDa antigen found on all stages of the parasite which also meets this criteria. The 16 kDa antigen extracted from mechanically transformed schistosomula and subsequently purified by immunoaffinity chromatography was shown to be a glycoprotein which incorporates both protein and carbohydrate epitopes. The latter, which include the target of a passively protective monoclonal antibody (Bickle et at., 1986), bind the lectins peanut and ricin agglutinin and are believed to incorporate the monosaccharide N- acetylgalactosamine O-linked to the peptide core. Attempts to determine the amino acid sequence of the antigen by gas phase NH2-terminal amino acid sequencing have also suggested that the protein moiety of the 16 kDa antigen is N-terminally blocked. The immunoaffinity purified 16 kDa antigen was subsequently used to immunise groups of mice in conjunction with a number of different adjuvants. Significant, albeit low, levels of resistance were achieved following immunisation with the 16 kDa molecule plus the nova some adjuvant formulation. Clones encoding the 15 kDa antigen were identified during the screening of a cDNA sporocyst library with sera specific for low molecular weight antigens. Sequence obtained for the antigen showed that it had some homology to members of a calcium binding protein superfamily, although the 15 kDa antigen itself was unable to bind calcium. The cDNA encoding this antigen was subsequently subcloned into a vector suitable for expression and the resulting fusion protein was used to immunise mice. Sera raised in these mice recognised the native 15 kDa antigen by Western blotting. However, the mice were not protected against a challenge infection

Schistosoma mansoni extracellular vesicles: immunobiology and vaccine efficacy

Desalegn Kifle characterized the molecular composition of extracellular vesicles secreted by Schistosoma mansoni parasites. He demonstrated their role in host-parasite communication via host cell gene regulation, as well as their vaccine potential. His findings could have potential impact on our understanding of schistosome biology and the wider field of molecular parasitology