Exploring types and functions of questions in police interviews

There is a proliferation of categorization schemes in the scientific literature that have mostly been developed from psychologists’ understanding of the nature of linguistic interactions. This has a led to problems in defining question types used by interviewers. Based on the principle that the overarching purpose of an interview is to elicit information and that questions can function both as actions in their own right and as vehicles for other actions, a Conversational Analysis approach was used to analyse a small number of police interviews. The analysis produced a different categorization of question types and, in particular, the conversational turns fell into two functional types: (i) Topic Initiation Questions and (ii) Topic Facilitation Questions. We argue that forensic interviewing requires a switch of focus from the ‘words’ used by interviewers in question types to the ‘function’ of conversational turns within interviews.

Investigation of the coordinated functional activities of cytochrome P450 3A4 and P-glycoprotein in limiting the absorption of xenobiotics in Caco-2 cells

The coordination of the functional activities of intestinal CYP3A4 and P-gp in limiting the absorption of xenobiotics in Caco-2 cells was investigated. Growing Caco-2 cells were exposed to increasing concentrations of doxorubicin (1-2 μM) in plastic flasks to encourage a subpopulation of cells, that displayed an intrinsically higher multidrug resistance (mdr) phenotype than the parent cells, to survive and grow. Doxorubicin-exposed (hereinafter referred to as type I cells) and nonexposed Caco-2 cells (parent cells) on collagen-coated inserts were also treated with either 0 (control) or 0.25 μM 1α,25-dihydroxyvitamin D3 to promote cellular CYP3A4 expression. Increased P-gp protein expression, as detected by Western blotting, was noted in type I cells (213±54.35%) compared to that of parent cells (100±6.05%). Furthermore, they retained significantly less [3H]vincristine sulphate (p<0.05), a P-gp substrate, after efflux (272.89±11.86 fmol/mg protein) than the parent cells (381.39±61.82 fmol/mg protein). The expression of CYP3A4 in parental cells after 1α,25-dihydroxyvitamin D3 treatment was quantified to be 76.2±7.6 pmol/mg protein and comparable with that found in human jejunal enterocytes (70.0±20.0 pmol/mg protein). Type I cells, however, expressed a very low quantity of CYP3A4 both before and after the treatment that was beyond the minimum detection limit of Western blotting. Functionally, the rates of 1-hydroxylation of midazolam by CYP3A for both cell types ranged from 257.0±20.0 to 1057.0±46.0 pmol/min/mg protein. Type I cells, although having a higher P-gp expression and activity comparatively, metabolized midazolam less extensively than the parent cells. The results suggested that there were noncoordinated functional activities of intestinal CYP3A4 and P-gp in Caco-2 cells, although they both functioned independently to minimize intestinal epithelial absorption of xenobiotics. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association.

Functional presynaptic HCN channels in the rat globus pallidus

Hyperpolarization-activated, cyclic nucleotide-gated cation (HCN) channels are expressed postsynaptically in the rodent globus pallidus (GP), where they play several important roles in controlling GP neuronal activity. To further elucidate the role of HCN channels in the GP, immunocytochemical and electrophysiological approaches were used to test the hypothesis that HCN channels are also expressed presynaptically on the local axon collaterals of GP neurons. At the electron microscopic level, immunoperoxidase labelling for HCN1 and HCN2 was localized in GP somata and dendritic processes, myelinated and unmyelinated axons, and axon terminals. One population of labelled terminals formed symmetric synapses with somata and proximal dendrites and were immunoreactive for parvalbumin, consistent with the axon collaterals of GABAergic GP projection neurons. In addition, labelling for HCN2 and, to a lesser degree, HCN1 was observed in axon terminals that formed asymmetric synapses and were immunoreactive for the vesicular glutamate transporter 2. Immunogold labelling demonstrated that HCN1 and HCN2 were located predominantly at extrasynaptic sites along the plasma membrane of both types of terminal. To determine the function of presynaptic HCN channels in the GP, we performed whole-cell recordings from GP neurons in vitro. Bath application of the HCN channel blocker ZD7288 resulted in an increase in the frequency of mIPSCs but had no effect on their amplitude, implying that HCN channels tonically regulate the release of GABA. Their presence, and predicted role in modulating transmitter release, represents a hitherto unidentified mechanism whereby HCN channels influence the activity of GP neurons. © The Authors (2007).

Optimization of chemical plant simulation using double collocation

A method has been constructed for the solution of a wide range of chemical plant simulation models including differential equations and optimization. Double orthogonal collocation on finite elements is applied to convert the model into an NLP problem that is solved either by the VF 13AD package based on successive quadratic programming, or by the GRG2 package, based on the generalized reduced gradient method. This approach is termed simultaneous optimization and solution strategy. The objective functional can contain integral terms. The state and control variables can have time delays. Equalities and inequalities containing state and control variables can be included into the model as well as algebraic equations and inequalities. The maximum number of independent variables is 2. Problems containing 3 independent variables can be transformed into problems having 2 independent variables using finite differencing. The maximum number of NLP variables and constraints is 1500. The method is also suitable for solving ordinary and partial differential equations. The state functions are approximated by a linear combination of Lagrange interpolation polynomials. The control function can either be approximated by a linear combination of Lagrange interpolation polynomials or by a piecewise constant function over finite elements. The number of internal collocation points can vary by finite elements. The residual error is evaluated at arbitrarily chosen equidistant grid-points, thus enabling the user to check the accuracy of the solution between collocation points, where the solution is exact. The solution functions can be tabulated. There is an option to use control vector parameterization to solve optimization problems containing initial value ordinary differential equations. When there are many differential equations or the upper integration limit should be selected optimally then this approach should be used. The portability of the package has been addressed converting the package from V AX FORTRAN 77 into IBM PC FORTRAN 77 and into SUN SPARC 2000 FORTRAN 77. Computer runs have shown that the method can reproduce optimization problems published in the literature. The GRG2 and the VF I 3AD packages, integrated into the optimization package, proved to be robust and reliable. The package contains an executive module, a module performing control vector parameterization and 2 nonlinear problem solver modules, GRG2 and VF I 3AD. There is a stand-alone module that converts the differential-algebraic optimization problem into a nonlinear programming problem.

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.

Development of a conceptual model of the soil-moisture-plant sub-system of the hydrological cycle

The soil-plant-moisture subsystem is an important component of the hydrological cycle. Over the last 20 or so years a number of computer models of varying complexity have represented this subsystem with differing degrees of success. The aim of this present work has been to improve and extend an existing model. The new model is less site specific thus allowing for the simulation of a wide range of soil types and profiles. Several processes, not included in the original model, are simulated by the inclusion of new algorithms, including: macropore flow; hysteresis and plant growth. Changes have also been made to the infiltration, water uptake and water flow algorithms. Using field data from various sources, regression equations have been derived which relate parameters in the suction-conductivity-moisture content relationships to easily measured soil properties such as particle-size distribution data. Independent tests have been performed on laboratory data produced by Hedges (1989). The parameters found by regression for the suction relationships were then used in equations describing the infiltration and macropore processes. An extensive literature review produced a new model for calculating plant growth from actual transpiration, which was itself partly determined by the root densities and leaf area indices derived by the plant growth model. The new infiltration model uses intensity/duration curves to disaggregate daily rainfall inputs into hourly amounts. The final model has been calibrated and tested against field data, and its performance compared to that of the original model. Simulations have also been carried out to investigate the effects of various parameters on infiltration, macropore flow, actual transpiration and plant growth. Qualitatively comparisons have been made between these results and data given in the literature.

The functional organisation of the fronto-temporal language system:evidence from syntactic and semantic ambiguity

Spoken language comprehension is known to involve a large left-dominant network of fronto-temporal brain regions, but there is still little consensus about how the syntactic and semantic aspects of language are processed within this network. In an fMRI study, volunteers heard spoken sentences that contained either syntactic or semantic ambiguities as well as carefully matched low-ambiguity sentences. Results showed ambiguity-related responses in the posterior left inferior frontal gyrus (pLIFG) and posterior left middle temporal regions. The pLIFG activations were present for both syntactic and semantic ambiguities suggesting that this region is not specialised for processing either semantic or syntactic information, but instead performs cognitive operations that are required to resolve different types of ambiguity irrespective of their linguistic nature, for example by selecting between possible interpretations or reinterpreting misparsed sentences. Syntactic ambiguities also produced activation in the posterior middle temporal gyrus. These data confirm the functional relationship between these two brain regions and their importance in constructing grammatical representations of spoken language.

Integrative bioinformatics for functional genorne annotation:trawling for G protein-coupled receptors

G protein-coupled receptors (GPCR) are amongst the best studied and most functionally diverse types of cell-surface protein. The importance of GPCRs as mediates or cell function and organismal developmental underlies their involvement in key physiological roles and their prominence as targets for pharmacological therapeutics. In this review, we highlight the requirement for integrated protocols which underline the different perspectives offered by different sequence analysis methods. BLAST and FastA offer broad brush strokes. Motif-based search methods add the fine detail. Structural modelling offers another perspective which allows us to elucidate the physicochemical properties that underlie ligand binding. Together, these different views provide a more informative and a more detailed picture of GPCR structure and function. Many GPCRs remain orphan receptors with no identified ligand, yet as computer-driven functional genomics starts to elaborate their functions, a new understanding of their roles in cell and developmental biology will follow.

The development of functional astrocyte-neuron networks derived from stem cells

There is currently great scientific and medical interest in the potential of tissue grown from stem cells. These cells present opportunities for generating model systems for drug screening and toxicological testing which would be expected to be more relevant to human outcomes than animal based tissue preparations. Newly realised astrocytic roles in the brain have fundamental implications within the context of stem cell derived neuronal networks. If the aim of stem cell neuroscience is to generate functional neuronal networks that behave as networks do in the brain, then it becomes clear that we must include and understand all the cellular components that comprise that network, and which are important to support synaptic integrity and cell to cell signalling. We have shown that stem cell derived neurons exhibit spontaneous and coordinated calcium elevations in clusters and in extended processes, indicating local and long distance signalling (1). Tetrodotoxin sensitive network activity could also be evoked by electrical stimulation. Similarly, astrocytes exhibit morphology and functional properties consistent with this glial cell type. Astrocytes also respond to neuronal activity and to exogenously applied neurotransmitters with calcium elevations, and in contrast to neurons, also exhibited spontaneous rhythmic calcium oscillations. Astroctyes also generate propagating calcium waves that are gap junction and purinergic signalling dependent. Our results show that stem cell derived astrocytes exhibit appropriate functionality and that stem cell neuronal networks interact with astrocytic networks in co-culture. Using mixed cultures of stem cell derived neurons and astrocytes, we have also shown both cell types also modulate their glucose uptake, glycogen turnover and lactate production in response to glutamate as well as increased neuronal activity (2). This finding is consistent with their neuron-astrocyte metabolic coupling thus demonstrating a tractable human model, which will facilitate the study of the metabolic coupling between neurons and astrocytes and its relationship with CNS functional issues ranging from plasticity to neurodegeneration. Indeed, cultures treated with oligomers of amyloid beta 1-42 (Aβ1-42) also display a clear hypometabolism, particularly with regard to utilization of substrates such as glucose (3). Both co-cultures of neurons and astrocytes and purified cultures of astrocytes showed a significant decrease in glucose uptake after treatment with 2 and 0.2 μmol/L Aβ at all time points investigated (p <0.01). In addition, a significant increase in the glycogen content of cells was also measured. Mixed neuron and astrocyte co-cultures as well as pure astrocyte cultures showed an initial decrease in glycogen levels at 6 hours compared with control at 0.2 μmol/L and 2 μmol/L P <0.01. These changes were accompanied by changes in NAD+/NADH (P<0.05), ATP (P<0.05), and glutathione levels (P<0.05), suggesting a disruption in the energy-redox axis within these cultures. The high energy demands associated with neuronal functions such as memory formation and protection from oxidative stress put these cells at particular risk from Aβ-induced hypometabolism. As numerous cell types interact in the brain it is important that any in vitro model developed reflects this arrangement. Our findings indicate that stem cell derived neuron and astrocyte networks can communicate, and so have the potential to interact in a tripartite manner as is seen in vivo. This study therefore lays the foundation for further development of stem cell derived neurons and astrocytes into therapeutic cell replacement and human toxicology/disease models. More recently our data provides evidence for a detrimental effect of Aβ on carbohydrate metabolism in both neurons and astrocytes. As a purely in vitro system, human stem cell models can be readily manipulated and maintained in culture for a period of months without the use of animals. In our laboratory cultures can be maintained in culture for up to 12 months months thus providing the opportunity to study the consequences of these changes over extended periods of time relevant to aspects of the disease progression time frame in vivo. In addition, their human origin provides a more realistic in vitro model as well as informing other human in vitro models such as patient-derived iPSC.