Optimization of Weighted Finite State Transducer for Speech Recognition

There is considerable interest in creating embedded, speech recognition hardware using the weighted finite state transducer (WFST) technique but there are performance and memory usage challenges. Two system optimization techniques are presented to address this; one approach improves token propagation by removing the WFST epsilon input arcs; another one-pass, adaptive pruning algorithm gives a dramatic reduction in active nodes to be computed. Results for memory and bandwidth are given for a 5,000 word vocabulary giving a better practical performance than conventional WFST; this is then exploited in an adaptive pruning algorithm that reduces the active nodes from 30,000 down to 4,000 with only a 2 percent sacrifice in speech recognition accuracy; these optimizations lead to a more simplified design with deterministic performance.

Conformation-specific crosslinking of mitochondrial complex I

Complex I is the only component of the eukaryotic respiratory chain of which no high-resolution structure is yet available. A notable feature of mitochondrial complex I is the so-called active/de-active conformational transition of the idle enzyme from the active (A) to the de-active, (D) form. Using an amine- and sulfhydryl-reactive crosslinker of 6.8 Å length (SPDP) we found that in the D-form of complex I the ND3 subunit crosslinked to the 39 kDa (NDUFA9) subunit. These proteins could not be crosslinked in the A-form. Most likely, both subunits are closely located in the critical junction region connecting the peripheral hydrophilic domain to the membrane arm of the enzyme where the entrance path for substrate ubiquinone is and where energy transduction takes place.

Early pain experience, child and family factors, as precursors of somatization:a prospective study of extremely premature and fullterm children

In a prospective study of 36 children who were extremely low birthweight (ELBW: <1000 g) preterm infants and 36 matched full-term controls, differences were found in somatization at age 4 1/2 years. Only children who had been extremely premature, and thereby experienced prolonged hospitalization and repeated medical intervention in infancy, had clinically high somatization scores on the Personality Inventory for Children. The combination of family relations at age 4 1/2 years, neonatal intensive care experience, poor maternal sensitivity to child cues in mother-child interaction observed at age 3 years, and child avoidance of touch or holding at age 3, predicted somatization scores, prior to school entry. Due to the known higher incidence of actual medical problems among children with a history of extreme prematurity, the high somatization ELBW children were compared with the normal somatization ELBW children. There were no differences in prevalence of actual medical problems between the 2 ELBW groups, and the importance of maternal factors in relation to somatization was confirmed. Child temperament at age 3, but not personality at 4 1/2, was related to somatization. The etiology of recurrent physical complaints of no known medical cause appears to be a multi-dimensional problem. Non-optimal parenting may contribute to the development of inappropriate strategies for coping with common pains of childhood, or of chronic pain patterns, in some children who have experienced prolonged or repeated pain as neonates.

Misfolding of galactose 1-phosphate uridylyltransferase can result in type I galactosemia

Type I galactosemia is a genetic disorder that is caused by the impairment of galactose-1-phosphate uridylyltransferase (GALT; EC 2.7.7.12). Although a large number of mutations have been detected through genetic screening of the human GALT (hGALT) locus, for many it is not known how they cause their effects. The majority of these mutations are missense, with predicted substitutions scattered throughout the enzyme structure and thus causing impairment by other means rather than direct alterations to the active site. To clarify the fundamental, molecular basis of hGALT impairment we studied five disease-associated variants p.D28Y, p.L74P, p.F171S, p.F194L and p.R333G using both a yeast model and purified, recombinant proteins. In a yeast expression system there was a correlation between lysate activity and the ability to rescue growth in the presence of galactose, except for p.R333G. Kinetic analysis of the purified proteins quantified each variant's level of enzymatic impairment and demonstrated that this was largely due to altered substrate binding. Increased surface hydrophobicity, altered thermal stability and changes in proteolytic sensitivity were also detected. Our results demonstrate that hGALT requires a level of flexibility to function optimally and that altered folding is the underlying reason of impairment in all the variants tested here. This indicates that misfolding is a common, molecular basis of hGALT deficiency and suggests the potential of pharmacological chaperones and proteostasis regulators as novel therapeutic approaches for type I galactosemia.

Simulations of Biased Agonists in the β2 Adrenergic Receptor with Accelerated Molecular Dynamics

The biased agonism of the G protein-coupled receptors (GPCRs), where in addition to a traditional G protein-signalling pathway a GPCR promotes intracellular signals though ß-arrestin, is a novel paradigm in pharmacology. Biochemical and biophysical studies have suggested that a GPCR forms a distinct ensemble of conformations signalling through the G protein and ß-arrestin. Here we report on the dynamics of the ß2 adrenergic receptor bound to the ß-arrestin and G protein biased agonists and the empty receptor to further characterize the receptor conformational changes caused by biased agonists. We use conventional and accelerated molecular dynamics (aMD) simulations to explore the conformational transitions of the GPCR from the active state to the inactive state. We found that aMD simulations enable monitoring the transition within the nanosecond timescale while capturing the known microscopic characteristics of the inactive states, such as the ionic lock, the inward position of F6.44, and water clusters. Distinct conformational states are shown to be stabilized by each biased agonist. In particular, in simulations of the receptor with the ß-arrestin biased agonist, N-cyclopentylbutanepherine we observe a different pattern of motions in helix 7 when compared to simulations with the G protein biased agonist, Salbutamol that involves perturbations of the network of interactions within the NPxxY motif. Understanding the network of interactions induced by biased ligands and the subsequent receptor conformational shifts will lead to development of more efficient drugs. © 2013 American Chemical Society

Physical activity and the rejuvenation of Connswater (PARC study): protocol for a natural experiment investigating the impact of urban regeneration on public health

Background: There is a dearth of evidence regarding the impact of urban regeneration projects on public health, particularly the nature and degree to which urban regeneration impacts upon health-related behaviour change. Natural experiment methodology enables comprehensive large-scale evaluations of such interventions. The Connswater Community Greenway in Belfast is a major urban regeneration project involving the development of a 9 km linear park, including the provision of new cycle paths and walkways. In addition to the environmental improvements, this complex intervention involves a number of programmes to promote physical activity in the regenerated area. The project affords a unique opportunity to investigate the public health impact of urban regeneration.

Methods/Design: The evaluation framework was informed by the socio-ecological model and guided by the RE-AIM Framework. Key components include: (1) a quasi-experimental before-and-after survey of the Greenway population (repeated cross-sectional design), in tandem with data from a parallel Northern Ireland-wide survey for comparison; (2) an assessment of changes in the local built environment and of walkability using geographic information systems; (3) semi-structured interviews with a purposive sample of survey respondents, and a range of community stakeholders, before and after the regeneration project; and (4) a cost-effectiveness analysis. The primary outcome is change in proportion of individuals identified as being regularly physically active, according to the current UK recommendations. The RE-AIM Framework will be used to make an overall assessment of the impact of the Greenway on the physical activity behaviour of local residents.

Discussion: The Connswater Community Greenway provides a significant opportunity to achieve long-term, population level behaviour change. We argue that urban regeneration may be conceptualised meaningfully as a complex intervention comprising multiple components with the potential, individually and interactively, to affect the behaviour of a diverse population. The development and implementation of our comprehensive evaluation framework reflects this complexity and illuminates an approach to the empirical, rigorous evaluation of urban regeneration. More specifically, this study will add to the much needed evidence-base about the impact of urban regeneration on public health as well as having important implications for the development of natural experiment methodology.

Electrochemical sensor for catechol and dopamine based on a catalytic molecularly imprinted polymer-conducting polymer hybrid recognition element

One of the difficulties with using molecularly imprinted polymers (MIPs) and other electrically insulating materials as the recognition element in electrochemical sensors is the lack of a direct path for the conduction of electrons from the active sites to the electrode. We have sought to address this problem through the preparation and characterization of novel hybrid materials combining a catalytic MIP, capable of oxidizing the template, catechol, with an electrically conducting polymer. In this way a network of "molecular wires" assists in the conduction of electrons from the active sites within the MIP to the electrode surface. This was made possible by the design of a new monomer that combines orthogonal polymerizable functionality; comprising an aniline group and a methacrylamide. Conducting films were prepared on the surface of electrodes (Au on glass) by electropolymerization of the aniline moiety. A layer of MIP was photochemically grafted over the polyaniline, via N,N'-diethyldithiocarbamic acid benzyl ester (iniferter) activation of the methacrylamide groups. Detection of catechol by the hybrid-MIP sensor was found to be specific, and catechol oxidation was detected by cyclic voltammetry at the optimized operating conditions: potential range -0.6 V to +0.8 V (vs Ag/AgCl), scan rate 50 mV/s, PBS pH 7.4. The calibration curve for catechol was found to be linear to 144 µM, with a limit of detection of 228 nM. Catechol and dopamine were detected by the sensor, whereas analogues and potentially interfering compounds, including phenol, resorcinol, hydroquinone, serotonin, and ascorbic acid, had minimal effect (=3%) on the detection of either analyte. Nonimprinted hybrid electrodes and bare gold electrodes failed to give any response to catechol at concentrations below 0.5 mM. Finally, the catalytic properties of the sensor were characterized by chronoamperometry and were found to be consistent with Michaelis-Menten kinetics. © 2009 American Chemical Society.

Preaggregated Ag Nanoparticles in Dry Swellable Gel Films for Off-the-Shelf Surface-Enhanced Raman Spectroscopy

Large, thin (50 mu m) dry polymer sheets containing numerous surface-enhanced Raman spectroscopy (SERS) active Ag nanopartide aggregates have been prepared by drying aqueous mixtures of hydroxyethylcelloulose (HEC) and preaggregated Ag colloid in 10 x 10 cm molds. In these dry films, the particle aggregates are protected from the environment during storage and are easy to handle; for example, they can be cut to size with scissors. When in use, the highly swellable HEC polymer allowed the films to rapidly absorb aqueous analyte solutions while simultaneously releasing the Ag nanoparticle aggregates to interact with the analyte and generate large SERS signals. Either the films could be immersed in the analyte solution or 5 mu L droplets were applied to the surface; in the latter method, the local swelling caused the active area to dome upward, but the swollen film remained physically robust and could be handled as required. Importantly, encapsulation and release did not significantly compromise the SERS performance of the colloid; the signals given by the swollen films were similar to the very high signals obtained from the parent citrate-reduced colloid and were an order of magnitude larger than a commercially available nanoparticle substrate. These "Poly-SERS" films retained 70% of their SERS activity after being stored for 1 year in air. The films were sufficiently homogeneous to give a standard deviation of 3.2% in the absolute signal levels obtained from a test analyte, primarily due to the films' ability to suppress "coffee ring" drying marks, which meant that quantitative analysis without an internal standard was possible. The majority of the work used aqueous thiophenol as the test analyte; however, preliminary studies showed that the Poly-SERS films could also be used with nonaqueous solvents and for a range of other analytes including theophylline, a therapeutic drug, at a concentration as low as 1.0 x 10(-5) mol dm(-3) (1.8 mg/dm(3)), well below the sensitivity required for theophylline monitoring where the target range is 10-20 mg/dm(3).

Turning Indium Oxide into a Superior Electrocatalyst:Deterministic Heteroatoms

The efficient electrocatalysts for many heterogeneous catalytic processes in energy conversion and storage systems must possess necessary surface active sites. Here we identify, from X-ray photoelectron spectroscopy and density functional theory calculations, that controlling charge density redistribution via the atomic-scale incorporation of heteroatoms is paramount to import surface active sites. We engineer the deterministic nitrogen atoms inserting the bulk material to preferentially expose active sites to turn the inactive material into a sufficient electrocatalyst. The excellent electrocatalytic activity of N-In2O3 nanocrystals leads to higher performance of dye-sensitized solar cells (DSCs) than the DSCs fabricated with Pt. The successful strategy provides the rational design of transforming abundant materials into high-efficient electrocatalysts. More importantly, the exciting discovery of turning the commonly used transparent conductive oxide (TCO) in DSCs into counter electrode material means that except for decreasing the cost, the device structure and processing techniques of DSCs can be simplified in future.

Effect of monovalent cations on the kinetics of hypoxic conformational change of mitochondrial complex i

Mitochondrial complex I is a large, membrane-bound enzyme central to energy metabolism, and its dysfunction is implicated in cardiovascular and neurodegenerative diseases. An interesting feature of mammalian complex I is the so-called A/D transition, when the idle enzyme spontaneously converts from the active (A) to the de-active, dormant (D) form. The A/D transition plays an important role in tissue response to ischemia and rate of the conversion can be a crucial factor determining outcome of ischemia/reperfusion. Here, we describe the effects of alkali cations on the rate of the D-to-A transition to define whether A/D conversion may be regulated by sodium.At neutral pH (7–7.5) sodium resulted in a clear increase of rates of activation (D-to-A conversion) while other cations had minor effects. The stimulating effect of sodium in this pH range was not caused by an increase in ionic strength. EIPA, an inhibitor of Na+/H+antiporters, decreased the rate of D-to-A conversion and sodium partially eliminated this effect of EIPA. At higher pH (> 8.0), acceleration of the D-to-A conversion by sodium was abolished, and all tested cations decreased the rate of activation, probably due to the effect of ionic strength.The implications of this finding for the mechanism of complex I energy transduction and possible physiological importance of sodium stimulation of the D-to-A conversion at pathophysiological conditions in vivo are discussed.

Architecture as Pedagogy: Alive and Kicking

This workshop draws on an emerging collaborative body of research by Lovett, Morrow and McClean that aims to understand architecture and its processes as a form of pedagogical practice: a civic pedagogy.

Architectural education can be valued not only as a process that delivers architecture-specific skills and knowledges, but also as a process that transforms people into critically active contributors to society. We are keen to examine how and where those skills are developed in architectural education and trace their existence and/or application within practice. We intend to examine whether some architectural and spatial practices are intrinsically pedagogical in their nature and how the level of involvement of clients, users and communities can mimic the project-based learning of architectural education – in particularly in the context of ‘live project learning’

1. This workshop begins with a brief discussion paper from Morrow that sets out the arguments behind why and how architecture can be understood as pedagogy. It will do so by presenting firstly the relationship between architectural practice and pedagogy, drawing out both contemporary and historical examples of architecture and architects acting pedagogically. It will also consider some other forms of creative practice that explicitly frame themselves pedagogically, and focus on participatory approaches in architectural practice that overlap with inclusive and live pedagogies, concluding with a draft and tentative abstracted pedagogical framework for architectural practice.

2. Lovett will examine practices of architectural operation that have a pedagogical approach, or which recognise within themselves an educational subtext/current. He is most interested in a 'liveness' beyond the 'Architectural Education' of university institutions. The presentation will question the scope for both spatial empowerment / agency and a greater understanding and awareness of the value of good design when operating as architects with participant-clients younger than 18, older than 25 or across varied parts of society. Positing that the learning might be greatest when there are no prescribed 'Learning Outcomes' and that such work might depend on risk-taking and playfulness, the presentation will be a curated showcase drawing on his own ongoing work.

Both brief presentations will inform the basis of the workshop’s discussion which hopes to draw on participants views and expereinces to enrich the research process. The intention is that the overall workshop will lead to a call for contributors and respondents to a forthcoming publication on ‘Architecture as Pedagogy’.

Responsibility and Well-Being: Resource Integration Under Responsibilization in Expert Services

Responsibilization, or the shift of functions and risks from providers and producers to consumers, has become an increasingly common policy in service systems and marketplaces (e.g., financial, health, governmental). As responsibilization is often considered synonymous with consumer agency and well-being, the authors take a transformative service research perspective and draw on resource integration literature to investigate whether responsibilization is truly associated with well-being. The authors focus on expert services, for which responsibilization concerns are particularly salient, and question whether this expanding policy is in the public interest. In the process, they develop a conceptualization of resource integration under responsibilization that includes three levels of actors (consumer, provider, and service system), the identification of structural tensions to resource integration, and three categories of resource integration practices (access, appropriation, and management) necessary to negotiate responsibilization. The findings have important implications for health care providers, public and institutional policy makers, and other service systems, all of which must pay more active attention to the challenges consumers face in negotiating responsibilization and the resulting well-being outcomes.

Responsibility and Well-being: Resource Integration under Responsibilization in Expert Services

Responsibilization, or the shift in functions and risks from providers and producers to the consumer, has become an increasingly common policy in service systems and marketplaces (e.g., financial, health, governmental). Responsibilization is often presented as synonymous with consumer agency and well-being. We take a transformative service research perspective and utilize the resource integration framework to investigate whether responsibilization is truly associated with well-being. We focus on expert services, where responsibilization concerns are particularly salient, and question whether this expanding policy is in the public interest. In the process, we develop a conceptualization of resource integration under responsibilization that includes three levels of actors (consumer, provider and service system), the identification of structural tensions to resource integration and three categories of resource integration practices (access, appropriation and management) necessary to negotiate responsibilization. Our findings have important implications for health care providers, public policy makers, and other service systems, all of which must pay more active attention to the challenges consumers face in negotiating responsibilization and the resulting well-being outcomes.

Evaluation of creative problem solving abilities in undergraduate structural engineers through interdisciplinary problem based learning

For a structural engineer, effective communication and interaction with architects cannot be underestimated as a key skill to success throughout their professional career. Structural engineers and architects have to share a common language and understanding of each other in order to achieve the most desirable architectural and structural designs. This interaction and engagement develops during their professional career but needs to be nurtured during their undergraduate studies. The objective of this paper is to present the strategies employed to engage higher order thinking in structural engineering students in order to help them solve complex problem-based learning (PBL) design scenarios presented by architecture students. The strategies employed were applied in the experimental setting of an undergraduate module in structural engineering at Queen’s University Belfast in the UK. The strategies employed were active learning to engage with content knowledge, the use of physical conceptual structural models to reinforce key concepts and finally, reinforcing the need for hand sketching of ideas to promote higher order problem-solving. The strategies employed were evaluated through student survey, student feedback and module facilitator (this author) reflection. The strategies were qualitatively perceived by the tutor and quantitatively evaluated by students in a cross-sectional study to help interaction with the architecture students, aid interdisciplinary learning and help students creatively solve problems (through higher order thinking). The students clearly enjoyed this module and in particular interacting with structural engineering tutors and students from another discipline