SSF Guidelines: the beauty of the small

An examination of the role of the Voluntary Guidelines for Securing Sustainable Small-scale Fisheries in the Context of Food Security and Poverty Eradication in the context of the small-sale fishery of Kerala, India.

Excision of Sleeping Beauty transposons: parameters and applications to gene therapy

A major problem in gene therapy is the determination of the rates at which gene transfer has occurred. Our work has focused on applications of the Sleeping Beauty (SB) transposon system as a non-viral vector for gene therapy. Excision of a transposon from a donor molecule and its integration into a cellular chromosome are catalyzed by SB transposase. In this study, we used a plasmid-based excision assay to study the excision step of transposition. We used the excision assay to evaluate the importance of various sequences that border the sites of excision inside and outside the transposon in order to determine the most active sequences for transposition from a donor plasmid. These findings together with our previous results in transposase binding to the terminal repeats suggest that the sequences in the transposon-junction of SB are involved in steps subsequent to DNA binding but before excision, and that they may have a role in transposase-transposon interaction. We found that SB transposons leave characteristically different footprints at excision sites in different cell types, suggesting that alternative repair machineries operate in concert with transposition. Most importantly, we found that the rates of excision correlate with the rates of transposition. We used this finding to assess transposition in livers of mice that were injected with the SB transposon and transposase. The excision assay appears to be a relatively quick and easy method to optimize protocols for delivery of genes in SB transposons to mammalian chromosomes in living animals. Copyright (C) 2004 John Wiley Sons, Ltd.

Gene transfer into genomes of human cells by the sleeping beauty transposon system

The Sleeping Beauty (SB) transposon system, derived from teleost fish sequences, is extremely effective at delivering DNA to vertebrate genomes, including those of humans. We have examined several parameters of the SB system to improve it as a potential, nonviral vector for gene therapy. Our investigation centered on three features: the carrying capacity of the transposon for efficient integration into chromosomes of HeLa cells, the effects of overexpression of the SB transposase gene on transposition rates, and improvements in the activity of SB transposase to increase insertion rates of transgenes into cellular chromosomes. We found that SB transposons of about 6 kb retained 50% of the maximal efficiency of transposition, which is sufficient to deliver 70-80% of identified human cDNAs with appropriate transcriptional regulatory sequences. Overexpression inhibition studies revealed that there are optimal ratios of SB transposase to transposon for maximal rates of transposition, suggesting that conditions of delivery of the two-part transposon system are important for the best gene-transfer efficiencies. We further refined the SB transposase to incorporate several amino acid substitutions, the result of which led to an improved transposase called SB11. With SB11 we are able to achieve transposition rates that are about 100-fold above those achieved with plasmids that insert into chromosomes by random recombination. With the recently described improvements to the transposon itself, the SB system appears to be a potential gene-transfer tool for human gene therapy.

Structure-function analysis of the inverted terminal repeats of the Sleeping Beauty transposon

Translocation of Sleeping Beauty (SB) transposon requires specific binding of SB transposase to inverted terminal repeats (ITRs) of about 230 bp at each end of the transposon, which is followed by a cut-and-paste transfer of the transposon into a target DNA sequence. The ITRs contain two imperfect direct repeats (DRs) of about 32 bp. The outer DRs are at the extreme ends of the transposon whereas the inner DRs are located inside the transposon, 165-166 bp from the outer DRs. Here we investigated the roles of the DR elements in transposition. Although there is a core transposase-binding sequence common to all of the DRs, additional adjacent sequences are required for transposition and these sequences vary in the different DRs. As a result, SB transposase binds less tightly to the outer DRs than to the inner DRs. Two DRs are required in each ITR for transposition but they are not interchangeable for efficient transposition. Each DR appears to have a distinctive role in transposition. The spacing and sequence between the DR elements in an ITR affect transposition rates, suggesting a constrained geometry is involved in the interactions of SB transposase molecules in order to achieve precise mobilization. Transposons are flanked by TA dinucleotide base-pairs that are important for excision; elimination of the TA motif on one side of the transposon significantly reduces transposition while loss of TAs on both flanks of the transposon abolishes transposition. These findings have led to the construction of a more advanced transposon that should be useful in gene transfer and insertional mutagenesis in vertebrates. (C) 2002 Elsevier Science Ltd. All rights reserved.

Representations and evolutionary operators for the scheduling of pump operations in water distribution networks.

Reducing the energy consumption of water distribution networks has never had more significance. The greatest energy savings can be obtained by carefully scheduling the operations of pumps. Schedules can be defined either implicitly, in terms of other elements of the network such as tank levels, or explicitly by specifying the time during which each pump is on/off. The traditional representation of explicit schedules is a string of binary values with each bit representing pump on/off status during a particular time interval. In this paper, we formally define and analyze two new explicit representations based on time-controlled triggers, where the maximum number of pump switches is established beforehand and the schedule may contain less switches than the maximum. In these representations, a pump schedule is divided into a series of integers with each integer representing the number of hours for which a pump is active/inactive. This reduces the number of potential schedules compared to the binary representation, and allows the algorithm to operate on the feasible region of the search space. We propose evolutionary operators for these two new representations. The new representations and their corresponding operations are compared with the two most-used representations in pump scheduling, namely, binary representation and level-controlled triggers. A detailed statistical analysis of the results indicates which parameters have the greatest effect on the performance of evolutionary algorithms. The empirical results show that an evolutionary algorithm using the proposed representations improves over the results obtained by a recent state-of-the-art Hybrid Genetic Algorithm for pump scheduling using level-controlled triggers.

Augmenting an artificial immune network using ordering, self-recognition and histo-compatibility operators.

Timmis J Neal M J and Hunt J. Augmenting an artificial immune network using ordering, self-recognition and histo-compatibility operators. In Proceedings of IEEE international conference of systems, man and cybernetics, pages 3821-3826, San Diego, 1998. IEEE.

The Dirichlet problem in convex bounded domains for operators with L^\infty-coefficients

M.Hieber, I.Wood: The Dirichlet problem in convex bounded domains for operators with L^\infty-coefficients, Diff. Int. Eq., 20, 7 (2007),721-734.

A Framework for the Scoring of Operators on the Search Space of Equivalence Classes of Bayesian Network Structures

R. Daly and Q. Shen. A Framework for the Scoring of Operators on the Search Space of Equivalence Classes of Bayesian Network Structures. Proceedings of the 2005 UK Workshop on Computational Intelligence, pages 67-74.

Boundary triplets and M-functions for non-selfadjoint operators, with applications to elliptic PDEs and block operator matrices

B.M. Brown, M. Marletta, S. Naboko, I. Wood: Boundary triplets and M-functions for non-selfadjoint operators, with applications to elliptic PDEs and block operator matrices, J. London Math. Soc., June 2008; 77: 700-718. The full text of this article will be made available in this repository in June 2009 Sponsorship: EPSRC,INTAS

The Dirichlet problem in convex bounded domains for operators with L8-coefficients

Wood, Ian; Hieber, M., (2007) 'The Dirichlet problem in convex bounded domains for operators with L8-coefficients', Differential and Integral Equations 20 pp.721-734 RAE2008

Birkhoff normal forms for Fourier integral operators II

Iantchenko, A.; Sj?strand, J., (2001) 'Birkhoff normal forms for Fourier integral operators II', American Journal of Mathematics 124(4) pp.817-850 RAE2008

Society, theatre and Social Work: beauty will save us

Three different worlds, sometimes concentric and often intersecting —society, theatre and the art of performance— and social work. Diverse worlds that live, reflect and self-reflect and interact, and can also afford an opportunity for meeting, misunderstanding and confrontation, and above all offer the possibility of profound change.This article considers the experience of a theatre company that has spent more than three years moving at the limits of these three universes. To these three worlds can be added an infinite number of words that fill them with meaning and significance: territory, meeting, diversity and search. An artistic experience that has chosen to focus on creating scenarios for debate and to examine the difficulties, the human contradictions and the constant and inexhaustible confrontation with human experience. At the heart of this theatrical activity is all of this, seeking the balance between narration, meeting, investigation and the artistic dimension. This meeting between society, theatre and social work also contains the search for sustainability of this cultural business, in an Italy that has been destroyed by a crisis that is not merely economic, but also of values and, above all, of role models. The guiding theme, though not always made explicit, is always present and essential: the search for beauty.