Pharmacological studies of 8-OH-DPAT-induced pupillary dilation in anesthetized rats

Serotonin (5-HT) receptor agonists have been reported to produce mydriasis in mice, and miosis in rabbits and humans. However, the underlying mechanisms for this action are unclear. This study was undertaken in an attempt to explore the mechanism by which 5-HT receptors are involved in the modulation of pupillary size in pentobarbital-anesthetized rats. Intravenous administration of the 5-HT receptor agonist, (2R)-(+)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT; 0.003-3 mg/kg), elicited dose-dependent pupillary dilation, which was not affected by section of the preganglionic cervical sympathetic nerve. 8-OH-DPAT-elicited mydriatic responses were attenuated by the selective 5-HT receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2- pyridinylcyclohexanecarboxamide maleate (WAY 100635; 0.3-1 mg/kg, i.v.), as well as by the selective a -adrenoceptor antagonist, (8aR,12aS,13aS)-5,8,8a,9,10,11,12,12a,13,13a-dechydro-3-methoxy-12- (ethylsulfonyl)-6H-isoquino[2,1-g][1,6]naphthyridine hydrochloride (RS 79948; 0.3 mg/kg, i.v.), but not by the selective a -adrenoceptor antagonist, prazosin (0.3 mg/kg, i.v.). Mydriatic responses elicited by the a -adrenoceptor agonist, guanabenz (0.003-0.3 mg/kg, i.v.), were not antagonized by WAY 100635 (0.3-1 mg/kg, i.v.). To determine whether central nervous system (CNS) 5-HT receptors, like a -adrenoceptors, are involved in reflex mydriasis, voltage response curves of pupillary dilation were constructed by stimulation of the sciatic nerve in anesthetized rats. WAY 100635 (1 mg/kg, i.v.) did not antagonize the evoked reflex mydriasis, which, however, was blocked by RS 79948 (0.3 mg/kg, i.v.). Taken together, these results suggest that 8-OH-DPAT produces pupillary dilation in anesthetized rats by stimulating CNS 5-HT receptors, which in turn trigger the release of norepinephrine, presumably from the locus coeruleus. The latter reduces parasympathetic neuronal tone to the iris sphincter muscle by stimulation of postsynaptic a - adrenoceptors within the Edinger-Westphal nucleus. Unlike a - adrenoceptors, 5-HT receptors in the CNS do not mediate reflex mydriasis evoked by sciatic nerve stimulation. © 2004 Elsevier B.V. All rights reserved.

Functional characterization of alpha-adrenoceptors mediating pupillary dilation in rats

Previously, we reported that the alpha(1A)-adrenoceptor, but not the alpha(1D)-adrenoceptor, mediates pupillary dilation elicited by sympathetic nerve stimulation in rats. This study was undertaken to further characterize the alpha-adrenoceptor subtypes mediating pupillary dilation in response to both neural and agonist activation. Pupillary dilator response curves were generated by intravenous injection of norepinephrine in pentobarbital-anesthetized rats. Involvement of alpha(1)-adrenoceptors was established as mydriatic responses were inhibited by systemic administration of nonselective alpha-adrenoceptor antagonists, phentolamine (0.3-3 mg/kg) and phenoxybenzamine (0.03-0.3 mg/kg), as well as by the selective alpha(1)-adrenoceptor antagonist, prazosin (0.3 mg/kg). The alpha(2)-adrenoceptor antagonist, rauwolscine (0.5 mg/kg), was without antagonistic effects. alpha(1A)-Adrenoceptor selective antagonists, 2-([2,6-dimethoxyphenoxyethyl]aminomethyl)-1,4-benzodioxane (WB-4101; 0.1-1 mg/kg) and 5-methylurapidil (0.1-1 mg/kg), the alpha(1B)-adrenoceptor selective antagonist, 4-amino-2-[4-[1-(benzyloxycarbonyl)-2(S)- [[(1,1-dimethylethyl)amino]carbonyl]-piperazinyl]-6,7-dimethoxyquinazoline (L-765314; 0.3-1 mg/kg), as well as the alpha(1D)-adrenoceptor selective antagonist, 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione (BMY-7378; 1 mg/kg), were used to delineate the adrenoceptor subtypes involved. Mydriatic responses to norepinephrine were significantly antagonized by intravenous administration of both WB-4101 and 5-methylurapidil, but neither by L-765314 nor by BMY-7378. L-765314 (0.3-3 mg/kg, i.v.) was also ineffective in inhibiting the mydriasis evoked by cervical sympathetic nerve stimulation. These results suggest that alpha(1B)-adrenoceptors do not mediate sympathetic mydriasis in rats, and that the alpha(1A)-adrenoceptor is the exclusive subtype mediating mydriatic responses in this species.

Studies of alpha-adrenoceptor antagonists on sympathetic mydriasis in rabbits

This study was undertaken to identify the alpha-adrenergic receptor type responsible for sympathetically evoked mydriasis in pentobarbital-anesthetized rabbits. Frequency-response curves of pupillary dilation were generated by stimulation of the preganglionic cervical sympathetic nerve (1-64 Hz). Evoked mydriatic responses were inhibited by systemic administration of nonselective alpha-adrenergic antagonists, phentolamine (0.3-10 mg/kg) and phenoxybenzamine (0.03-0.3 mg/kg), as well as the selective alpha(1)-adrenergic antagonist, prazosin (0.1-1 mg/kg). The alpha(2)-adrenergic antagonist, RS 79948 (0.3 mg/kg, i.v.) was without inhibitory effect, but potentiated the mydriatic response. In addition, the selective alpha(1A)-adrenoceptor antagonist, 5-methylurapidil (0.1-1 mg/kg, i.v.), antagonized the elicited mydriasis in a dose-dependent fashion. Unlike previous observations that prazosin does not block the adrenoceptor in rabbit iris dilator muscle, our results suggest that prazosin is effective in inhibiting neuronally elicited mydriasis in this species, and that alpha(1A)-adrenoceptors appear to mediate the response.

Contribution of primary motor cortex to compensatory balance reactions

Background: Rapid compensatory arm reactions represent important response strategies following an unexpected loss of balance. While it has been assumed that early corrective actions arise largely from sub-cortical networks, recent findings have prompted speculation about the potential role of cortical involvement. To test the idea that cortical motor regions are involved in early compensatory arm reactions, we used continuous theta burst stimulation (cTBS) to temporarily suppress the hand area of primary motor cortex (M1) in participants prior to evoking upper limb balance reactions in response to whole body perturbation. We hypothesized that following cTBS to the M1 hand area evoked EMG responses in the stimulated hand would be diminished. To isolate balance reactions to the upper limb participants were seated in an elevated tilt-chair while holding a stable handle with both hands. The chair was held vertical by a magnet and was triggered to fall backward unpredictably. To regain balance, participants used the handle to restore upright stability as quickly as possible with both hands. Muscle activity was recorded from proximal and distal muscles of both upper limbs.

Results: Our results revealed an impact of cTBS on the amplitude of the EMG responses in the stimulated hand muscles often manifest as inhibition in the stimulated hand. The change in EMG amplitude was specific to the target hand muscles and occasionally their homologous pairs on the non-stimulated hand with no consistent effects on the remaining more proximal arm muscles.

Conclusions: Present findings offer support for cortical contributions to the control of early compensatory arm reactions following whole-body perturbation.

The impact of global routing on the performance of NoCs in FPGAs

With the over-provisioned routing resource on FPGA, the topology choice for NoC implementation on FPGA is more flexible than on ASIC. However, it is well understood that the global wire routing impacts the performance of NoC on FPGA because the topology is routed by using fixed routing fabric. An important question that arises is: will the benefit of diameter reduction by using a highly connective topology outweigh the impact of global routing? To answer this question, we investigate FPGA based packet switched NoC implementations with different sizes and topologies, and quantitatively measure the impact of global routing to each of these networks. The result shows that with sufficient routing resources on modern FPGA, the global routing is not on the critical path of the system, and thus is not a dominating factor for the performance of practical multi-hop NoC system. © 2011 IEEE.

Transgressing Contemporary Boundaries:The Narrator as True Custodian of Cultural Knowledge in Ulster Society

Historically in Gaelic culture, the bard was greatly valued and admired as an important and integral part of society. Travelled, schooled and specifically trained in their art, the bard helped ensure identity and reassurance for Gaelic families by grounding them both temporarily and spatially into their landscape. Entrusted with the duty and responsibility of recording place and event, the bards worked without writing and by transgressing man-made boundaries, travelled throughout the land weaving their histories into the very fabric of society.

Now no longer with us, we find ourselves without the distinguished chronicler to undertake this duty. Yet the responsibility of the Gaelic bard is one still shared by all artists today; to facilitate memory and identity, whether good or bad. Many Ulster writers, by happenstance and geography have found themselves located in a place of painful histories. An immediate difficulty for those local writers becomes manifest by being intrinsically implicated into those histories – whilst having first-hand knowledge and comprehension beyond that of the outsider, the local writer is automatically damned by association and relationship, thereby tarnishing their voice in comparison to the perceived impartiality of others.
Some writers however have successfully sought ways to escape this limitation and have worked in ways that can transgress the restrictions of prejudgement. John Hewitt, by purposely becoming a self-imposed tourist was able to distance himself to write impartially about the past, recognising that ’the place without its ghosts is a barren place.’1 In ‘The Colony’,2 tradition, peoples and mapping of the land are all narrated by Hewitt in a similar way to the Gaelic bardic topographic poems of Sean O'Dubhagain and Giolla Na Naomh O'Huidhrin3 in compiling a rich cultural atlas.

Similarly the Belfast poet and novelist Ciaran Carson also writes and records the city from an intermediary position; that of translator. Mediating between reader and aisling,4 Carson himself takes the reader on a journey into name, meaning, time and place, focusing primarily on the city of Belfast, familiar in name but impenetrable in depth to most.

Furthermore, this once-forgotten tradition to chronicle is now being continued by the new breed of Irish crime writers where the likes of Brian McGilloway, Stuart Neville and Adrian McKinty can, by way of the crime novel, accurately record contemporary society. Thus, ghost estates, listed buildings, archaeological digs, street and city have all provided setting and subject matter for recent novels. Moreover by choosing the ‘outsider from within’ as their chief protagonist, whether detective or criminal, each author is able to transgress the boundaries of prejudice and preconception that hinder genuine understanding and knowledge.

Looking in turn at the Gaelic bard, the twentieth century Ulster poet and the new breed of Irish crime writer, the authors will outline the real value of the narrator, by being able to act as cultural transgressor beyond the seeming and alleged as the true chronicler in society, and then with specific reference to city and countryside in Ireland, as a valuable custodian of knowledge in architecture and place.

Keywords
Architecture, Crime Fiction, Cultural Atlas, Place, Poetry.

1 From ‘The Bloody Brae’, a one act play written by John Hewitt in the 1930’s.
2 Hewitt, J. (1968) published in Collected Poems 1932-67. London:McGibbon & Kee.
3 Lengthy and detailed medieval Gaelic poems composed in the fourteenth and fifteenth centuries first edited by John O'Donovan in 1862 for the Irish Archaeological and Celtic Society in Dublin.
4 The aisling is the Irish song or poem genre when the poet is visited by their muse in a daydream or dream-vision state.

GABAergic control of arteriolar diameter in the rat retina

Purpose: To investigate the role of γ-aminobutryic acid (GABA) in the regulation of arteriolar diameter in the rat retina.

Methods.: The actions of GABA on arteriolar diameter were examined using ex vivo retinal whole-mount preparations and isolated vessel segments. In most experiments, arterioles were partially preconstricted with endothelin (Et)-1. The expression levels of GABAA and GABAB receptors on isolated rat retinal Müller cells were assessed by immunohistochemistry.

Results.: GABA (0.1–1 mM) evoked vasodilation or vasoconstriction of arterioles in whole-mount preparations. No such effects were observed with isolated vessel segments. In whole mount samples, the GABAA receptor agonist muscimol caused vasomotor responses in only a small proportion of vessels. In contrast, arteriolar responses to the GABAB receptor agonists baclofen and SKF97541 more closely resembled those observed with GABA. No responses were seen with the GABAC receptor agonist 5-methylimidazoleacetic acid. GABA-induced vasodilator responses were, for the most part, repeatable in the presence of the GABAA receptor antagonist bicuculline. These responses, however, were completely blocked in the presence of the GABAB receptor inhibitor 2-hydroxysaclofen. Strong immunolabeling for both GABAA and GABAB receptors was detected in isolated Müller cells. In the absence of Et-1–induced preconstriction, most vessels were unresponsive to bicuculline or 2-hydroxysaclofen.

Conclusions.: GABA exerts complex effects on arteriolar diameter in the rat retina. These actions appear largely dependent upon the activation of GABAB receptors in the retinal neuropile, possibly those located on perivascular Müller cells. Despite these findings, endogenous GABA appears to contribute little to the regulation of basal arteriolar diameter in the rat retina.

Speed of processing in the primary motor cortex: A continuous theta burst stimulation study

‘Temporally urgent’ reactions are extremely rapid, spatially precise movements that are evoked following discrete stimuli. The involvement of primary motor cortex (M1) and its relationship to stimulus intensity in such reactions is not well understood. Continuous theta burst stimulation (cTBS) suppresses focal regions of the cortex and can assess the involvement of motor cortex in speed of processing. The primary objective of this study was to explore the involvement of M1 in speed of processing with respect to stimulus intensity. Thirteen healthy young adults participated in this experiment. Behavioral testing consisted of a simple button press using the index finger following median nerve stimulation of the opposite limb, at either high or low stimulus intensity. Reaction time was measured by the onset of electromyographic activity from the first dorsal interosseous (FDI) muscle of each limb. Participants completed a 30 min bout of behavioral testing prior to, and 15 min following, the delivery of cTBS to the motor cortical representation of the right FDI. The effect of cTBS on motor cortex was measured by recording the average of 30 motor evoked potentials (MEPs) just prior to, and 5 min following, cTBS. Paired t-tests revealed that, of thirteen participants, five demonstrated a significant attenuation, three demonstrated a significant facilitation and five demonstrated no significant change in MEP amplitude following cTBS. Of the group that demonstrated attenuated MEPs, there was a biologically significant interaction between stimulus intensity and effect of cTBS on reaction time and amplitude of muscle activation. This study demonstrates the variability of potential outcomes associated with the use of cTBS and further study on the mechanisms that underscore the methodology is required. Importantly, changes in motor cortical excitability may be an important determinant of speed of processing following high intensity stimulation.

Human parietal and primary motor cortical interactions are selectively modulated during the transport and grip formation of goal-directed hand actions

Posterior parietal cortex (PPC) constitutes a critical cortical node in the sensorimotor system in which goal-directed actions are computed. This information then must be transferred into commands suitable for hand movements to the primary motor cortex (M1). Complexity arises because reach-to-grasp actions not only require directing the hand towards the object (transport component), but also preshaping the hand according to the features of the object (grip component). Yet, the functional influence that specific PPC regions exert over ipsilateral M1 during the planning of different hand movements remains unclear in humans. Here we manipulated transport and grip components of goal-directed hand movements and exploited paired-pulse transcranial magnetic stimulation (ppTMS) to probe the functional interactions between M1 and two different PPC regions, namely superior parieto-occipital cortex (SPOC) and the anterior region of the intraparietal sulcus (aIPS), in the left hemisphere. We show that when the extension of the arm is required to contact a target object, SPOC selectively facilitates motor evoked potentials, suggesting that SPOC-M1 interactions are functionally specific to arm transport. In contrast, a different pathway, linking the aIPS and ipsilateral M1, shows enhanced functional connections during the sensorimotor planning of grip. These results support recent human neuroimaging findings arguing for specialized human parietal regions for the planning of arm transport and hand grip during goal-directed actions. Importantly, they provide new insight into the causal influences these different parietal regions exert over ipsilateral motor cortex for specific types of planned hand movements

Improvement of the efficiency of energy transfer in the hydro-entanglement process

Hydro-entanglement is a versatile process for bonding non-woven fabrics by the use of fine, closely-spaced, high-velocity jets of water to rearrange and entangle arrays of fibres. The cost of the process mainly depends on the amount of energy consumed. Therefore, the economy of the process is highly affected by optimisation of the energy required. In this paper a parameter called critical pressure is introduced which is indicative of the energy level requirement. The results of extensive experimental work are reported and analysed to give a clear understanding of the effect of the web and fibre properties on the critical pressure in the hydro-entanglement process. Furthermore, different energy-transfer distribution schemes are tested on various fabrics. The optimum scheme which involves the lowest energy consumption and the best fabric properties is identified. © 2001 Published by Elsevier Science Ltd. All rights reserved.

Application of fibre assemblies as damping elements in the automotive industry

This investigation aims to characterise the damping properties of the nonwoven materials with potential applications in automotive and aerospace industry. Nonwovens are a popular choice for many applications due to their relatively low manufacturing cost and unique properties. It is known that nonwovens are efficient energy dispersers for certain applications such as acoustic damping and ballistic impact. It is anticipated that these energy absorption properties could eventually be used to provide damping for mechanical vibrations. However the behaviour of nonwovens under dynamic load and vibration has not been investigated before. Therefore we intend to highlight these aspects of the behaviour of the nonwovens through this research. In order to obtain an insight to the energy absorption properties of the nonwoven fabrics, a range of tests has been performed. Forced vibration of the cantilever beam is used to explore damping over a range of resonance modes and input amplitudes. The tests are conducted on aramid, glass fibre and polyester fabrics with a range of area densities and various coatings. The tests clarified the general dynamic behaviour of the fabrics tested and the possible response in more real application condition as well. The energy absorption in both thickness and plane of the fabric is tested. The effects of the area density on the results are identified. The main absorption mechanism is known to be the friction. The frictional properties are improved by using a smaller fibre denier and increasing fibre length, this is a result of increasing contact surface between fibres. It is expected the increased friction result in improving damping. The results indicate different mechanism of damping for fiber glass fabrics compared to the aramid fabrics. The frequency of maximum efficiency of damping is identified for the fabrics tested. These can be used to recommend potential applications.

Sustainable Technoscientific Development and the Innovator Citizen

Sustainable development could provide a critical foil for individual
and especially collective reflection on the normative
direction, ends and means employed by societies, particularly
around the economy, its technology and resource-intensive
orientation and configuration with ecosystems. However,
although sustainable development is a constitutional objective
of the EU, its implementation in strategies and policies reveals
a much narrower meaning. By framing sustainable development
as ecological modernisation on the basis of technoscientific
innovation, and by imagining citizens as entrepreneurs in a
knowledge-based European economy, openings for democratic
experimentation and social innovation are limited and even
forestalled. In addition, the disruptive and transformational
potential of citizenship is stymied. Still, sustainable development
has resonance within citizenship and human rights
discourses that provide important resources for the fashioning
of common understanding. These are valuable supplements to
the repertoire of European citizenship that could help to embed
sustainable development in the social fabric and generate
alternative imaginaries and futures of a sustainable Europe.

Implementation of a non-orthogonal model for the finite element simulation of textile composite draping

In the pursuit of producing high quality, low-cost composite aircraft structures, out-of-autoclave manufacturing processes for textile reinforcements are being simulated with increasing accuracy. This paper focuses on the continuum-based, finite element modelling of textile composites as they deform during the draping process. A non-orthogonal constitutive model tracks yarn orientations within a material subroutine developed for Abaqus/Explicit, resulting in the realistic determination of fabric shearing and material draw-in. Supplementary material characterisation was experimentally performed in order to define the tensile and non-linear shear behaviour accurately. The validity of the finite element model has been studied through comparison with similar research in the field and the experimental lay-up of carbon fibre textile reinforcement over a tool with double curvature geometry, showing good agreement.

Belfast: A study on built heritage

This book is a compilation of 5th year architecture dissertations dealing with the value of the existing built fabric of Belfast city center and the potential reuse of that fabric. This hopefully begins a tradition of disseminating the extensive work students undertake in describing, understanding and analyzing built heritage in Belfast and Northern Ireland. It does not aim to be innovative in its findings nor revolutionary in its position, but hopefully it will be a seed in a quest to get architecture students involved in their city and the value of the existing built fabric.

MicroRNA-199b modulates vascular cell fate during iPS cell differentiation by targeting the notch ligand jagged1 and enhancing VEGF signaling

Aims: Recent ability to derive endothelial cells (ECs) from induced pluripotent stem (iPS) cells holds a great therapeutic potential for personalised medicine and stem cell therapy. We aimed that better understanding of the complex molecular signals that are evoked during iPS cell differentiation towards ECs may allow specific targeting of their activities to enhance cell differentiation and promote tissue regeneration.

Methods and Results: In this study we have generated mouse iPS cells from fibroblasts using established protocol. When iPS cells were cultivated on type IV mouse collagen-coated dishes in differentiation medium, cell differentiation toward vascular lineages were observed. To study the molecular mechanisms of iPS cell differentiation, we found that miR-199b is involved in EC differentiation. A step-wise increase in expression of miR-199 was detected during EC differentiation. Notably, miR-199b targeted the Notch ligand JAG1, resulting in VEGF transcriptional activation and secretion through the transcription factor STAT3. Upon shRNA-mediated knockdown of the Notch ligand JAG1, the regulatory effect of miR-199b was ablated and there was robust induction of STAT3 and VEGF during EC differentiation. Knockdown of JAG1 also inhibited miR-199b-mediated inhibition of iPS cell differentiation towards SMCs. Using the in vitro tube formation assay and implanted Matrigel plugs, in vivo, miR-199b also regulated VEGF expression and angiogenesis.

Conclusions: This study indicates a novel role for miR-199b as a regulator of the phenotypic switch during vascular cell differentiation derived from iPS cells by regulating critical signaling angiogenic responses.