Fundamental Bounds and Approaches to Sequence Reconstruction from Nanopore Sequencers

Nanopore sequencers are emerging as promising new platforms for high-throughput sequencing. As with other technologies, sequencer errors pose a major challenge for their effective use. In this paper, we present a novel information theoretic analysis of the impact of insertion-deletion (indel) errors in nanopore sequencers. In particular, we consider the following problems: (i) for given indel error characteristics and rate, what is the probability of accurate reconstruction as a function of sequence length; (ii) what is the number of `typical' sequences within the distortion bound induced by indel errors; (iii) using replicated extrusion (the process of passing a DNA strand through the nanopore), what is the number of replicas needed to reduce the distortion bound so that only one typical sequence exists within the distortion bound. Our results provide a number of important insights: (i) the maximum length of a sequence that can be accurately reconstructed in the presence of indel and substitution errors is relatively small; (ii) the number of typical sequences within the distortion bound is large; and (iii) replicated extrusion is an effective technique for unique reconstruction. In particular, we show that the number of replicas is a slow function (logarithmic) of sequence length -- implying that through replicated extrusion, we can sequence large reads using nanopore sequencers. Our model considers indel and substitution errors separately. In this sense, it can be viewed as providing (tight) bounds on reconstruction lengths and repetitions for accurate reconstruction when the two error modes are considered in a single model.Comment: 12 pages, 5 figure

How to Knit Your Own Markov Blanket

Hohwy (Hohwy 2016, Hohwy 2017) argues there is a tension between the free energy principle and leading depictions of mind as embodied, enactive, and extended (so-called ‘EEE1 cognition’). The tension is traced to the importance, in free energy formulations, of a conception of mind and agency that depends upon the presence of a ‘Markov blanket’ demarcating the agent from the surrounding world. In what follows I show that the Markov blanket considerations do not, in fact, lead to the kinds of tension that Hohwy depicts. On the contrary, they actively favour the EEE story. This is because the Markov property, as exemplified in biological agents, picks out neither a unique nor a stationary boundary. It is this multiplicity and mutability– rather than the absence of agent-environment boundaries as such - that EEE cognition celebrates

Reframing the L2 learning experience as narrative reconstructions of classroom learning

In this study we investigate the situated and dynamic nature of the L2 learning experience through a newly-purposed instrument called the Language Learning Story Interview, adapted from McAdams’ life story interview (2007). Using critical case sampling, data were collected from an equal number of learners of various L2s (e.g., Arabic, English, Mandarin, Spanish) and analyzed using qualitative comparative analysis (Rihoux & Ragin, 2009). Through our data analysis, we demonstrate how language learners construct overarching narratives of the L2 learning experience and what the characteristic features and components that make up these narratives are. Our results provide evidence for prototypical nuclear scenes (McAdams et al., 2004) as well as core specifications and parameters of learners’ narrative accounts of the L2 learning experience. We discuss how these shape motivation and language learning behavior

Scalable, Time-Responsive, Digital, Energy-Efficient Molecular Circuits using DNA Strand Displacement

We propose a novel theoretical biomolecular design to implement any Boolean circuit using the mechanism of DNA strand displacement. The design is scalable: all species of DNA strands can in principle be mixed and prepared in a single test tube, rather than requiring separate purification of each species, which is a barrier to large-scale synthesis. The design is time-responsive: the concentration of output species changes in response to the concentration of input species, so that time-varying inputs may be continuously processed. The design is digital: Boolean values of wires in the circuit are represented as high or low concentrations of certain species, and we show how to construct a single-input, single-output signal restoration gate that amplifies the difference between high and low, which can be distributed to each wire in the circuit to overcome signal degradation. This means we can achieve a digital abstraction of the analog values of concentrations. Finally, the design is energy-efficient: if input species are specified ideally (meaning absolutely 0 concentration of unwanted species), then output species converge to their ideal concentrations at steady-state, and the system at steady-state is in (dynamic) equilibrium, meaning that no energy is consumed by irreversible reactions until the input again changes. Drawbacks of our design include the following. If input is provided non-ideally (small positive concentration of unwanted species), then energy must be continually expended to maintain correct output concentrations even at steady-state. In addition, our fuel species - those species that are permanently consumed in irreversible reactions - are not "generic"; each gate in the circuit is powered by its own specific type of fuel species. Hence different circuits must be powered by different types of fuel. Finally, we require input to be given according to the dual-rail convention, so that an input of 0 is specified not only by the absence of a certain species, but by the presence of another. That is, we do not construct a "true NOT gate" that sets its output to high concentration if and only if its input's concentration is low. It remains an open problem to design scalable, time-responsive, digital, energy-efficient molecular circuits that additionally solve one of these problems, or to prove that some subset of their resolutions are mutually incompatible.Comment: version 2: the paper itself is unchanged from version 1, but the arXiv software stripped some asterisk characters out of the abstract whose purpose was to highlight words. These characters have been replaced with underscores in version 2. The arXiv software also removed the second paragraph of the abstract, which has been (attempted to be) re-inserted. Also, although the secondary subject is "Soft Condensed Matter", this classification was chosen by the arXiv moderators after submission, not chosen by the authors. The authors consider this submission to be a theoretical computer science paper

Crossing the river by feeling for stones: a new approach to exporting creative content to China?

We have all heard the statistics about China\u27s stellar growth and the large market for UK creative industries. But the trade numbers paint a different picture, suggesting that the UK is punching below its weight. This is not altogether surprising. Doing business in emerging markets like China is fraught with risk and uncertainty which can overwhelm even the most canny operations.  This paper examines what more can be done and highlights the novel role that digital social networks could play in overcoming these obstacles and helping UK creative businesses unlock export opportunities to China. ------------------- We have all heard the statistics. About how China is forecast to overtake the US to be the largest economy in the world by 2027.1 How China already has 277 million mobile web users, of which 45 per cent use their handsets to access music and 21 per cent video games.2 How more than 300 million Chinese are studying English.3 How Chinese e–commerce is predicted to triple by 2015, when sales could hit $420 billion – 20 per cent higher than the projection for the US market.4 And how, at 67,300, China sends more students to UK universities than any other country in the world.5 These dizzying numbers should mean there is a particularly large market for the UK’s creative industries, right? The trade statistics suggest not. According to UNCTAD, in 2010 the UK’s share of creative goods exports to China was just 1.4 per cent, compared with a 4.8 per cent share in world creative goods exports.6 UK exports of creative goods to China totalled$140 million, lower than not only Japan ($900 million), the US ($800 million) and Singapore ($520 million), but also France ($224 million), Germany ($325 million) and Italy ($474 million).7 With the exception of Japan and Germany, the value of UK exports of creative goods grew at a slower rate than in all these countries between 2002 and 2010. These trade statistics are not without their problems – they exclude all creative services, for example – nonetheless they indicate that the UK’s creative industries are punchingbelow their weight in Chinese markets.   &nbsp