An investigation into formal and functional characteristics of qualifications in legislative writing and its application to English for academic legal purposes.

The present investigation is based on a linguistic analysis of the 'Housing Act 1980' and attempts to examine the role of qualifications in the structuring of the legislative statement. The introductory chapter isolates legislative writing as a "sub-variety “of legal language and provides an overview of the controversies surrounding the way it is written and the problems it poses to its readers. Chapter two emphasizes the limitations of the available work on the description of language-varieties for the analysis of legislative writing and outlines the approach adopted for the present analysis. This chapter also gives some idea of the information-structuring of legislative provisions and establishes qualification as a key element in their textualisation. The next three chapters offer a detailed account of the ten major qualification-types identified in the corpus, concentrating on the surface form they take, the features of legislative statements they textualize and the syntactic positions to which they are generally assigned in the statement of legislative provisions. The emerging hypotheses in these chapters have often been verified through a specialist reaction from a Parliamentary Counsel, largely responsible for the writing of the ‘Housing Act 1980’• The findings suggest useful correlations between a number of qualificational initiators and the various aspects of the legislative statement. They also reveal that many of these qualifications typically occur in those clause-medial syntactic positions which are sparingly used in other specialist discourse, thus creating syntactic discontinuity in the legislative sentence. Such syntactic discontinuities, on the evidence from psycholinguistic experiments reported in chapter six, create special problems in the processing and comprehension of legislative statements. The final chapter converts the main linguistic findings into a series of pedagogical generalizations, offers indications of how this may be applied in EALP situations and concludes with other considerations of possible applications.

Studies on the luminance-related characteristics of the transient pattern reversal electroretinogram

The electroretinogram evoked by reversal pattern stimulation (rPERG) is known to contain both pattern contrast and luminance related components. The retinal mechanisms of the transient rPERGs subserving these functional characteristics are the main concern in the present studies. Considerable attention has been paid to the luminance-related characteristics of the response. The transient PERGs were found to consist of two subsequent processes using low frequency attenuation analysis. The processes overlapped and the individual difference in each process timings formed the major cause for the variations of the negative potential waveform of the transient rPERGs. Attention has been paid to those having ‘notch’ type of variation. Under different contrast levels, the amplitudes of the positive and negative potentials were linearly increased with higher contrast level and the negative potential showed a higher sensitivity to contrast changes and higher contrast gain. Under lower contrast levels, the decreased amplitudes made the difference in the timing course of the positive and negative processes evident, interpreting the appearance of the notch in some cases. Visual adaptation conditions for recording the transient rPERG were discussed. Another effort was to study the large variation of the transient rPERGs (especially the positive potential, P50) in the elderly who’s distant and near visual acuity were normal. It was found that reduction of retinal illumination contributed mostly to the P50 amplitude loss and contrast loss mostly to the negative potential (N95) amplitude loss. Senile miosis was thought to have little effect on the reduction of the retinal illumination, while the changes in the optics of the eye was probably the major cause for it, which interpreted the larger individual variation of the P50 amplitude of the elderly PERGs. Convex defocus affected the transient rPERGs more effectively than concave lenses, especially the N95 amplitude in the elderly. The disability of accommodation and the type and the degree of subjects’ ametropia should be taken into consideration when the elderly rPERGs were analysed.

The second intracellular loop of the calcitonin gene-related peptide receptor provides molecular determinants for signal transduction and cell surface expression

The calcitonin gene-related peptide (CGRP) receptor is a heterodimer of a family B G-protein-coupled receptor, calcitonin receptor-like receptor (CLR), and the accessory protein receptor activity modifying protein 1. It couples to Gs, but it is not known which intracellular loops mediate this. We have identified the boundaries of this loop based on the relative position and length of the juxtamembrane transmembrane regions 3 and 4. The loop has been analyzed by systematic mutagenesis of all residues to alanine, measuring cAMP accumulation, CGRP affinity, and receptor expression. Unlike rhodopsin, ICL2 of the CGRP receptor plays a part in the conformational switch after agonist interaction. His-216 and Lys-227 were essential for a functional CGRP-induced cAMP response. The effect of (H216A)CLR is due to a disruption to the cell surface transport or surface stability of the mutant receptor. In contrast, (K227A)CLR had wild-type expression and agonist affinity, suggesting a direct disruption to the downstream signal transduction mechanism of the CGRP receptor. Modeling suggests that the loop undergoes a significant shift in position during receptor activation, exposing a potential G-protein binding pocket. Lys-227 changes position to point into the pocket, potentially allowing it to interact with bound G-proteins. His-216 occupies a position similar to that of Tyr-136 in bovine rhodopsin, part of the DRY motif of the latter receptor. This is the first comprehensive analysis of an entire intracellular loop within the calcitonin family of G-protein-coupled receptor. These data help to define the structural and functional characteristics of the CGRP-receptor and of family B G-protein-coupled receptors in general. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.

Contrast- and illumination-invariant object recognition from active sensation

It has been suggested that the deleterious effect of contrast reversal on visual recognition is unique to faces, not objects. Here we show from priming, supervised category learning, and generalization that there is no such thing as general invariance of recognition of non-face objects against contrast reversal and, likewise, changes in direction of illumination. However, when recognition varies with rendering conditions, invariance may be restored, and effects of continuous learning may be reduced, by providing prior object knowledge from active sensation. Our findings suggest that the degree of contrast invariance achieved reflects functional characteristics of object representations learned in a task-dependent fashion.

Stimuli of varying spatial scale induce gamma activity with distinct temporal characteristics in human visual cortex

Gamma activity to stationary grating stimuli was studied non-invasively using MEG recordings in humans. Using a spatial filtering technique, we localized gamma activity to primary visual cortex. We tested the hypothesis that spatial frequency properties of visual stimuli may be related to the temporal frequency characteristics of the associated cortical responses. We devised a method to assess temporal frequency differences between stimulus-related responses that typically exhibit complex spectral shapes. We applied this methodology to either single-trial (induced) or time-averaged (evoked) responses in four frequency ranges (0-40, 20-60, 40-80 and 60-100 Hz) and two time windows (either the entire duration of stimulus presentation or the first second following stimulus onset). Our results suggest that stimuli of varying spatial frequency induce responses that exhibit significantly different temporal frequency characteristics. These effects were particularly accentuated for induced responses in the classical gamma frequency band (20-60 Hz) analyzed over the entire duration of stimulus presentation. Strikingly, examining the first second of the responses following stimulus onset resulted in significant loss in stimulus specificity, suggesting that late signal components contain functionally relevant information. These findings advocate a functional role of gamma activity in sensory representation. We suggest that stimulus specific frequency characteristics of MEG signals can be mapped to processes of neuronal synchronization within the framework of coupled dynamical systems.

Dissociating the spatio-temporal characteristics of cortical neuronal activity associated with human volitional swallowing in the healthy adult brain

Human swallowing represents a complex highly coordinated sensorimotor function whose functional neuroanatomy remains incompletely understood. Specifically, previous studies have failed to delineate the temporo-spatial sequence of those cerebral loci active during the differing phases of swallowing. We therefore sought to define the temporal characteristics of cortical activity associated with human swallowing behaviour using a novel application of magnetoencephalography (MEG). In healthy volunteers (n = 8, aged 28-45), 151-channel whole cortex MEG was recorded during the conditions of oral water infusion, volitional wet swallowing (5 ml bolus), tongue thrust or rest. Each condition lasted for 5 s and was repeated 20 times. Synthetic aperture magnetometry (SAM) analysis was performed on each active epoch and compared to rest. Temporal sequencing of brain activations utilised time-frequency wavelet plots of regions selected using virtual electrodes. Following SAM analysis, water infusion preferentially activated the caudolateral sensorimotor cortex, whereas during volitional swallowing and tongue movement, the superior sensorimotor cortex was more strongly active. Time-frequency wavelet analysis indicated that sensory input from the tongue simultaneously activated caudolateral sensorimotor and primary gustatory cortex, which appeared to prime the superior sensory and motor cortical areas, involved in the volitional phase of swallowing. Our data support the existence of a temporal synchrony across the whole cortical swallowing network, with sensory input from the tongue being critical. Thus, the ability to non-invasively image this network, with intra-individual and high temporal resolution, provides new insights into the brain processing of human swallowing. © 2004 Elsevier Inc. All rights reserved.

Functional characterization of GABAergic pallidopallidal and striatopallidal synapses in the rat globus pallidus in vitro

As a central integrator of basal ganglia function, the external segment of the globus pallidus (GP) plays a critical role in the control of voluntary movement. Driven by intrinsic mechanisms and excitatory glutamatergic inputs from the subthalamic nucleus, GP neurons receive GABAergic inhibitory input from the striatum (Str-GP) and from local collaterals of neighbouring pallidal neurons (GP-GP). Here we provide electrophysiological evidence for functional differences between these two inhibitory inputs. The basic synaptic characteristics of GP-GP and Str-GP GABAergic synapses were studied using whole-cell recordings with paired-pulse and train stimulation protocols and variance-mean (VM) analysis. We found (i) IPSC kinetics are consistent with local collaterals innervating the soma and proximal dendrites of GP neurons whereas striatal inputs innervate more distal regions. (ii) Compared to GP-GP synapses Str-GP synapses have a greater paired-pulse ratio, indicative of a lower probability of release. This was confirmed using VM analysis. (iii) In response to 20 and 50 Hz train stimulation, GP-GP synapses are weakly facilitatory in 1 mm external calcium and depressant in 2.4 mm calcium. This is in contrast to Str-GP synapses which display facilitation under both conditions. This is the first quantitative study comparing the properties of GP-GP and Str-GP synapses. The results are consistent with the differential location of these inhibitory synapses and subtle differences in their release probability which underpin stable GP-GP responses and robust short-term facilitation of Str-GP responses. These fundamental differences may provide the physiological basis for functional specialization.

Neuromagnetic investigations of functional organisation within human visual cortex

This thesis describes a series of experimental investigations into the functional organisation of human visual cortex using neuromagnetometry.This technique combines good spatial and temporal resolution enabling identification of the location and temporal response characteristics of cortical neurones within alert humans. To activate different neuronal populations and cortical areas a range of stimuli were used, the parameters of which were selected to match the known physiological properties of primate cortical neurones. In one series of experiments the evoked magnetic response was recorded to isoluminant red/green gratings. Co-registration of signal and magnetic resonance image data indicated a contribution to the response from visual areas V1, V2 and V4. To investigate the spatio-temporal characteristics of neurones within area V1 the evoked response was recorded for a range of stimulus spatial and temporal frequencies. The response to isoluminant red/green gratings was dominated by a major component which was found to have bandpass spatial frequency tuning with a peak at 1-2 cycles/degree, falling to the level of the noise at 6-8 cycles/degree. The temporal frequency tuning characteristics of the response showed bimodal sensitivity with peaks at 0-1Hz and 4Hz. In a further series of experiments the luminance evoked response was recorded to red/black, yellow/black and achromatic gratings and in all cases was found to be more complex than the isoluminant chromatic response, comprising up to three distinct components. The major response peak showed bandpass spatial frequency tuning characteristics, peaking at 6-8 cycles/degree, falling to the level of the noise at 12-16 cycles/degree. The results provide evidence to suggest that within area V1 the same neuronal population encodes both chromatic and luminance information and has spatial frequency tuning properties consistent with single-opponent cells. Furthermore, the results indicate that cells within area V1 encode chromatic motion information over a wide range of temporal frequencies with temporal response characteristics suggestive of the existence of a sub-population of cells sensitive to high temporal frequencies.

Disciplinary talk:a systemic functional exploration of university seminar discussions

Despite the growth of spoken academic corpora in recent years, relatively little is known about the language of seminar discussions in higher education. This thesis compares seminar discussions across three disciplinary areas. The aim of this thesis is to uncover the functions and patterns of talk used in different disciplinary discussions and to highlight language on a macro and micro level that would be useful for materials design and teaching purposes. A framework for identifying and analysing genres in spoken language based on Hallidayan Systemic Functional Linguistics (SFL) is used. Stretches of talk sharing a similar purpose and predictable functional staging, termed Discussion Macro Genres (DMGs) are identified. Language is compared across DMGs and across disciplines through use of corpus techniques in conjunction with SFL genre theory. Data for the study comprises just over 180,000 tokens and is drawn from the British Academic Spoken English corpus (BASE), recorded at two universities in the UK. The discipline areas investigated are Arts and Humanities, Social Sciences and Physical Sciences. Findings from this study make theoretical, empirical and methodological contributions to the field of spoken EAP. The empirical findings are firstly, that the majority of the seminar discussion can be assigned to one of the three main DMG in the corpus: Responding, Debating and Problem Solving. Secondly, it characterises each discipline area according to two DMGs. Thirdly, the majority of the discussion is non-oppositional in nature, suggesting that ‘debate’ is not the only form of discussion that students need to be prepared for. Finally, while some characteristics of the discussion are tied to the DMG and common across disciplines, others are discipline specific. On a theoretical level, this study shows that an SFL genre model for investigating spoken discourse can be successfully extended to investigate longer stretches of discourse than have previously been identified. The methodological contribution is to demonstrate how corpus techniques can be combined with SFL genre theory to investigate extended stretches of spoken discussion. The thesis will be of value to those working in the field of teaching spoken EAP/ ESAP as well as to materials developers.

Reactive processing of polymers:effect of bifunctional and tri-functional comonomers on melt grafting of glycidyl methacrylate onto polypropylene

Two reactive comonomers, divinyl benzene (DVB) and trimethylolpropane triacrylate (TRIS), were evaluated for their role in effecting the melt free radical grafting reaction of the monomer glycidyl methacrylate (GMA) onto polypropylene (PP). The characteristics of the GMA-grafting systems in the presence and absence of DVB or TRIS were examined and compared in terms of the yield of the grafting reaction and the extent of the main side reactions, namely homopolymerisation of GMA (poly-GMA) and polymer degradation, using different chemical compositions of the reactive systems and processing conditions. In the absence of the comonomers, i.e. in a conventional system, high initiator concentrations of peroxides were typically required to achieve the highest possible GMA grafting levels which were found to be generally low. Concomitantly, both poly-GMA and degradation of the polymer by chain scission takes place with increasing initiator amounts. On the other hand, the presence of a small amount of the comonomers, DVB or Tris, in the GMA-grafting system, was shown to bring about a significant increase in the grafting level paralleled by a large reduction in poly-GMA and PP degradation. In the presence of these highly reactive comonomers, the optimum grafting system requires a much lower concentration of the peroxide initiator and, consequently, would lead to the much lower degree of polymer degradation observed in these systems. The differences in the effects of the presence of DVB and that of TRIS in the grafting systems on the rate of the GMA-grafting and homopolymerisation reactions, and the extent of PP degradation (through melt flow changes), were compared and contrasted with a conventional GMA-grafting system.

Physical and functional characterisation of apoptotic cell-derived extracellular vesicles

Damaged, aged or unwanted cells are removed from the body by an active process known as apoptosis. This highly orchestrated programme results in the exposure of 'flags' at the dying cell surface and the release of attractive signals to recruit phagocytes. Together these changes ensure efficient phagocytic removal of dying cells and prevention of inflammatory and autoimmune disorders. Extracellular vesicles (EV) are released from a variety of cells (both viable and apoptotic) and they serve as a novel means of intercellular communication. They range in size: 70-100nm ('exosomes') through 100-1000nm ('microparticles') to large vesicles released from dying cells ('apoptotic bodies'). Release of apoptotic cell-derived extracellular vesicles (acdEV) of less than 1000nm is an important mechanism by which phagocytes are attracted to sites of cell death. Using a variety of approaches we characterize the release, physical characteristics and function of acdEV. Using fluorescence microscopy we demonstrate release of ICAM-3 on acdEV from dying leukocytes and, through the use of resistive pulse technology (qNano, IZON Science), we accurately size and quantitate acdEV release. The function of acdEV is revealed through the use of both horizontal chemotaxis assays (Dunn chambers) and vertical transwell migration assays (Cell-IQ, CM Technologies). These assays reveal potent chemoattractive capacity of acdEV and associated ICAM-3. Additionally we demonstrate an additional novel function of acdEV as anti-inflammatory immune-modulators. These data support an integrated approach to the physical and functional analyses of EV.

G-protein-coupled receptor solubilization and purification for biophysical analysis and functional studies, in the total absence of detergent

G-protein coupled receptors (GPCRs) constitute the largest class of membrane proteins and are a major drug target. A serious obstacle to studying GPCR structure/function characteristics is the requirement to extract the receptors from their native environment in the plasma membrane, coupled with the inherent instability of GPCRs in the detergents required for their solubilization. In the present study, we report the first solubilization and purification of a functional GPCR [human adenosine A2A receptor (A2AR)], in the total absence of detergent at any stage, by exploiting spontaneous encapsulation by styrene maleic acid (SMA) co-polymer direct from the membrane into a nanoscale SMA lipid particle (SMALP). Furthermore, the A2AR-SMALP, generated from yeast (Pichia pastoris) or mammalian cells, exhibited increased thermostability (∼5°C) compared with detergent [DDM (n-dodecyl-β-D-maltopyranoside)]-solubilized A2AR controls. The A2AR-SMALP was also stable when stored for prolonged periods at 4°C and was resistant to multiple freeze-thaw cycles, in marked contrast with the detergent-solubilized receptor. These properties establish the potential for using GPCR-SMALP in receptor-based drug discovery assays. Moreover, in contrast with nanodiscs stabilized by scaffold proteins, the non-proteinaceous nature of the SMA polymer allowed unobscured biophysical characterization of the embedded receptor. Consequently, CD spectroscopy was used to relate changes in secondary structure to loss of ligand binding ([³H]ZM241385) capability. SMALP-solubilization of GPCRs, retaining the annular lipid environment, will enable a wide range of therapeutic targets to be prepared in native-like state to aid drug discovery and understanding of GPCR molecular mechanisms.

Discovering biomarkers for antidepressant response:protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort

Background: Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers ("biomarkers") of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. Methods: CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10-20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2-10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. Discussion: From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research. Trial registration: ClinicalTrials.gov identifier NCT01655706. Registered July 27, 2012.

Clinical characteristics and benefit of cataract intervention amongst UK domiciliary eye care recipients

Purpose: Given the ageing UK population and the high prevalence of activity-limiting illness and disability in the over 65s, the demand for domiciliary eye care services is set to grow significantly. Over 400,000 NHS domiciliary eye examinations are conducted each year, yet minimal research attention has been directed to this mode of practice or patient needs amongst this group. The study aimed to compare clinical characteristics and benefits of cataract surgery between conventional in-practice patients and domiciliary service users. Methods: Clinical characteristics were compared between patients in North-West England receiving NHS domiciliary eye care services (n = 197; median age 76.5 years), and an age-matched group of conventional in-practice patients (n = 107; median age 74.6 years). Data including reason for visit; logMAR uncorrected and best corrected distance (UDVA and CDVA) and near acuities (UNVA and CNVA); presence of ocular pathology and examination outcome were documented retrospectively. To compare the benefit of cataract surgery in terms of functional capacity between the patient groups, individuals undergoing routine referral for first-eye surgery completed the VF-14 questionnaire pre-operatively, and at 6 weeks post-operatively. Results: UDVA was similar between the two groups (median 0.48 and 0.50 logMAR in the domiciliary and practice groups, P = 0.916); CDVA was significantly worse in the domiciliary group (median 0.18 vs 0.08 logMAR, P<0.001), who were more likely to have clinically-significant cataract. Both groups showed similar improvements in VF-14 scores following cataract surgery (mean gains 24.4 ± 11.7, and 31.5 ± 14.7 points in the in-practice and domiciliary groups, respectively. P = 0.312). Conclusions: Patients receiving domiciliary eye care services are more likely to have poorer corrected vision than in-practice patients of a similar age, partly due to a higher prevalence of significant cataract. Despite limitations in their activities due to illness and disability, domiciliary patients experience similar gains in self-reported functional capacity following cataract surgery