Follow-ups and interpreter-mediated discourse

The edited volume documents the proceedings of the ESF workshop "Follow-ups across discourse domains: a cross-cultural exploration of their forms and functions". It examines the forms and functions of the dialogue act of a follow-up, viz. accepting or challenging a prior communicative act, in political discourse across spoken and written dialogic genres. Specifically, it considers (1) the discourse domains of political interviews, editorials, op-eds and discussion forums, (2) their sequential organization as regards the status of initial (or 1st order) follow-up, a follow-up of a prior follow-up (2nd order follow-up), or nth-order follow-up, and (3) their discursive realization as regards degrees of indirectness and responsiveness which are conceptualized as a continuum along the lines of degrees of explicitness and degrees of responsiveness. The chapters come from the fields of linguistics, discourse analysis, socio-pragmatics, communication, political science and psychology, examining the heterogeneous field of political discourse and its manifestation in diverse discourse genres with respect to evasiveness, indirectness and redundancy in mediated political discourse, professional discourse, discourse identity and doing politics, to name but the most prominent questions.

The integration of ProxiMAX randomisation with CIS display for the high-throughput production of novel peptides

Saturation mutagenesis is a powerful tool in modern protein engineering. This can allow the analysis of potential new properties thus allowing key residues within a protein to be targeted and randomised. However, the creation of large libraries using conventional saturation mutagenesis with degenerate codons (NNN or NNK) has inherent redundancy and disparities in residue representation. In this we describe the combination of ProxiMAX randomisation and CIS display for the use of generating novel peptides. Unlike other methods ProxiMAX randomisation does not require any intricate chemistry but simply utilises synthetic DNA and molecular biology techniques. Designed ‘MAX’ oligonucleotides were ligated, amplified and digested in an iterative cycle. Results show that randomised ‘MAX’ codons can be added sequentially to the base sequence creating a series of randomised non-degenerate codons that can subsequently be inserted into a gene. CIS display (Isogencia, UK) is an in vitro DNA based screening method that creates a genotype to phenotype link between a peptide and the nucleic acid that encodes it. The use of straight forward in vitro transcription/translation and other molecular biology techniques permits ease of use along with flexibility making it a potent screening technique. Using ProxiMAX randomisation in combination with CIS display, the aim is to produce randomised anti-nerve growth factor (NGF) and calcitonin gene-related (CGRP) peptides to demonstrate the high-throughput nature of this combination.

Approximate axial symmetries from continuous time quantum walks

The analysis of complex networks is usually based on key properties such as small-worldness and vertex degree distribution. The presence of symmetric motifs on the other hand has been related to redundancy and thus robustness of the networks. In this paper we propose a method for detecting approximate axial symmetries in networks. For each pair of nodes, we define a continuous-time quantum walk which is evolved through time. By measuring the probability that the quantum walker to visits each node of the network in this time frame, we are able to determine whether the two vertices are symmetrical with respect to any axis of the graph. Moreover, we show that we are able to successfully detect approximate axial symmetries too. We show the efficacy of our approach by analysing both synthetic and real-world data. © 2012 Springer-Verlag Berlin Heidelberg.

Health and population effects of rare gene knockouts in adult humans with related parents

Examining complete gene knockouts within a viable organism can inform on gene function. We sequenced the exomes of 3222 British Pakistani-heritage adults with high parental relatedness, discovering 1111 rare-variant homozygous genotypes with predicted loss of gene function (knockouts) in 781 genes. We observed 13.7% fewer than expected homozygous knockout genotypes, implying an average load of 1.6 recessive-lethal-equivalent LOF variants per adult. Linking genetic data to lifelong health records, knockouts were not associated with clinical consultation or prescription rate. In this dataset we identified a healthy PRDM9 knockout mother, and performed phased genome sequencing on her, her child and controls, which showed meiotic recombination sites localized away from PRDM9-dependent hotspots. Thus, natural LOF variants inform upon essential genetic loci, and demonstrate PRDM9 redundancy in humans.

Developing a new SVPWM control strategy for open-winding brushless doubly fed reluctance generators

In this paper, a new open-winding control strategy is proposed for a brushless doubly fed reluctance generator (BDFRG) used for stand-alone wind turbine or ship generators. The BDFRG is characterized with two windings on the stator: a power winding and a control winding. The control winding is fed with dual two-level three-phase converters, and a vector control scheme based on space vector pulsewidth modulation is designed. Compared with traditional three-level inverter systems, the dc-link voltage and the voltage rating of power devices in the proposed system are reduced by 50% while still greatly improving the reliability, redundancy, and fault tolerance of the proposed system by increasing the switching modes. Its performance is evaluated by simulation in MATLAB/Simulink and an experimental study on a 42-kW prototype machine.

Weakly-constrained codes for suppression of patterning effects in digital communications

We propose weakly-constrained stream and block codes with tunable pattern-dependent statistics and demonstrate that the block code capacity at large block sizes is close to the the prediction obtained from a simple Markov model published earlier. We demonstrate the feasibility of the code by presenting original encoding and decoding algorithms with a complexity log-linear in the block size and with modest table memory requirements. We also show that when such codes are used for mitigation of patterning effects in optical fibre communications, a gain of about 0.5dB is possible under realistic conditions, at the expense of small redundancy 10%). © 2006 IEEE.

The integration of ProxiMAX randomisation with CIS display for the production of novel peptides

Saturation mutagenesis is a powerful tool in modern protein engineering, which permits key residues within a protein to be targeted in order to potentially enhance specific functionalities. However, the creation of large libraries using conventional saturation mutagenesis with degenerate codons (NNN or NNK/S) has inherent redundancy and consequent disparities in codon representation. Therefore, both chemical (trinucleotide phosphoramidites) and biological methods (sequential, enzymatic single codon additions) of non-degenerate saturation mutagenesis have been developed in order to combat these issues and so improve library quality. Large libraries with multiple saturated positions can be limited by the method used to screen them. Although the traditional screening method of choice, cell-dependent methods, such as phage display, are limited by the need for transformation. A number of cell-free screening methods, such as CIS display, which link the screened phenotype with the encoded genotype, have the capability of screening libraries with up to 1014 members. This thesis describes the further development of ProxiMAX technology to reduce library codon bias and its integration with CIS display to screen the resulting library. Synthetic MAX oligonucleotides are ligated to an acceptor base sequence, amplified, and digested, subsequently adding a randomised codon to the acceptor, which forms an iterative cycle using the digested product of the previous cycle as the base sequence for the next. Initial use of ProxiMAX highlighted areas of the process where changes could be implemented in order to improve the codon representation in the final library. The refined process was used to construct a monomeric anti-NGF peptide library, based on two proprietary dimeric peptides (Isogenica) that bind NGF. The resulting library showed greatly improved codon representation that equated to a theoretical diversity of ~69%. The library was subsequently screened using CIS display and the discovered peptides assessed for NGF-TrkA inhibition by ELISA. Despite binding to TrkA, these peptides showed lower levels of inhibition of the NGF-TrkA interaction than the parental dimeric peptides, highlighting the importance of dimerization for inhibition of NGF-TrkA binding.

Direct power control with common mode voltage elimination for open-winding brushless doubly-fed wind power generators

In this paper, a new open-winding control strategy is proposed for a brushless doubly-fed reluctance generator (BDFRG) applicable for wind turbines. The BDFRG control winding is fed via a dual two-level three-phase converter using a single dc bus. Direct power control based on maximum power point tracking with common mode voltage elimination is designed, which not only the active and reactive power is decoupled, but the reliability and redundancy are all improved greatly by increasing the switching modes of operation, while DC-link voltage and rating of power devices decreased by 50% comparing to the traditional three-level converter systems. Consequently its effectiveness is evaluated by simulation tests based on a 42-kW prototype generator.

Weakly-constrained codes for suppression of patterning effects in digital communications

We propose weakly-constrained stream and block codes with tunable pattern-dependent statistics and demonstrate that the block code capacity at large block sizes is close to the the prediction obtained from a simple Markov model published earlier. We demonstrate the feasibility of the code by presenting original encoding and decoding algorithms with a complexity log-linear in the block size and with modest table memory requirements. We also show that when such codes are used for mitigation of patterning effects in optical fibre communications, a gain of about 0.5dB is possible under realistic conditions, at the expense of small redundancy (≈10%). © 2010 IEEE