Distributed temperature sensor based on Brillouin loss in an optical fibre for transient threshold monitoring

A distributed temperature sensor for transient threshold monitoring with a 22 km sensing length, based on the Brillouin loss in standard communications fibre, is demonstrated. The system can be used for real-time monitoring of a preset temperature threshold. Good S/N ratios were achieved with only 8���16 sample averages giving a response time of 2 to 4 s with a temperature uncertainty of ��1 ��C.

GABAB receptor-mediated activation of astrocytes by gamma-hydroxybutyric acid

The gamma-aminobutyric acid (GABA) metabolite gamma-hydroxybutyric acid (GHB) shows a variety of behavioural effects when administered to animals and humans, including reward/addiction properties and absence seizures. At the cellular level, these actions of GHB are mediated by activation of neuronal GABAB receptors (GABABRs) where it acts as a weak agonist. Because astrocytes respond to endogenous and exogenously applied GABA by activation of both GABAA and GABABRs, here we investigated the action of GHB on astrocytes on the ventral tegmental area (VTA) and the ventrobasal (VB) thalamic nucleus, two brain areas involved in the reward and proepileptic action of GHB, respectively, and compared it with that of the potent GABABR agonist baclofen. We found that GHB and baclofen elicited dose-dependent (ED50: 1.6 mM and 1.3 ��M, respectively) transient increases in intracellular Ca2+ in VTA and VB astrocytes of young mice and rats, which were accounted for by activation of their GABABRs and mediated by Ca2+ release from intracellular store release. In contrast, prolonged GHB and baclofen exposure caused a reduction in spontaneous astrocyte activity and glutamate release from VTA astrocytes. These findings have key (patho)physiological implications for our understanding of the addictive and proepileptic actions of GHB.

Refractive error, cognitive demand and nearwork-induced transient myopia

Purpose. Whereas many previous studies have identified the association between sustained near work and myopia, few have assessed the influence of concomitant levels of cognitive effort. This study investigates the effect of cognitive effort on near-work induced transient myopia (NITM). Methods. Subjects comprised of six early onset myopes (EOM; mean age 23.7 yrs; mean onset 10.8 yrs), six late-onset myopes (LOM; mean age 23.2 yrs; mean onset 20.0 yrs) and six emmetropes (EMM; mean age 23.8 yrs). Dynamic, monocular, ocular accommodation was measured with the Shin-Nippon SRW-5000 autorefractor. Subjects engaged passively or actively in a 5 minute arithmetic sum checking task presented monocularly on an LCD monitor via a Badal optical system. In all conditions the task was initially located at near (4.50 D) and immediately following the task instantaneously changed to far (0.00 D) for a further 5 minutes. The combinations of active (A) and passive (P) cognition were randomly allocated as P:P; A:P; A:A; P:A. Results. For the initial near task, LOMs were shown to have a significantly less accurate accommodative response than either EOMs or EMMs (p < 0.001). For the far task, post hoc analyses for refraction identified EOMs as demonstrating significant NITM compared to LOMs (p < 0.05), who in turn showed greater NITM than EMMs (p < 0.001). The data show that for EOMs the level of cognitive activity operating during the near and far tasks determines the persistence of NITM; persistence being maximal when active cognition at near is followed by passive cognition at far. Conclusions. Compared with EMMs, EOMs and LOMs are particularly susceptible to NITM such that sustained near vision reduces subsequent accommodative accuracy for far vision. It is speculated that the marked NITM found in EOM may be a consequence of the crystalline lens thinning shown to be a developmental feature of EOM. Whereas the role of small amounts of retinal defocus in myopigenesis remains equivocal, the results show that account needs to be taken of cognitive demand in assessing phenomena such as NITM.

Drug-induced bilateral transient myopia with the sulphonamide sulphasalazine

Whereas there are numerous reported ocular side effects from systemic sulpha medication, most are rare and reversible, with myopia being the most common reaction observed. A case report is presented of sudden bilateral onset of -1.0 DS of myopia (from -3.0 to -4.0 DS) in a young adult female following the addition of a sulphonamide (sulphasalazine) to oral non-steroidal anti-inflammatory treatment (meloxicam) for rheumatoid arthritis. The myopia regressed to -3.50 DS after 2 weeks when all medication was withdrawn and stabilised at this level when subsequent treatment was resumed after 8 weeks with the non-steroidal anti-inflammatory drug celecoxib. The case indicates that account needs to be taken of the possibility that relatively modest myopic shifts encountered in young adult contact lens wearers may be associated with concomitant systemic medication. �� 2003 The College of Optometrists.

The role of Ca2+ in the generation of spontaneous astrocytic Ca2+ oscillations

Astrocytes in the rat thalamus display spontaneous [Ca2+]i oscillations that are due to intracellular release, but are not dependent on neuronal activity. In this study we have investigated the mechanisms involved in these spontaneous [Ca2+]i oscillations using slices loaded with Fluo-4 AM (5����M) and confocal microscopy. Bafilomycin A1 incubation had no effect on the number of spontaneous [Ca2+]i oscillations indicating that they were not dependent on vesicular neurotransmitter release. Oscillations were also unaffected by ryanodine. Phospholipase C (PLC) inhibition decreased the number of astrocytes responding to metabotropic glutamate receptor (mGluR) activation but did not reduce the number of spontaneously active astrocytes, indicating that [Ca2+]i increases are not due to membrane-coupled PLC activation. Spontaneous [Ca2+]i increases were abolished by an IP3 receptor antagonist, whilst the protein kinase C (PKC) inhibitor chelerythrine chloride prolonged their duration, indicating a role for PKC and inositol 1,4,5,-triphosphate receptor activation. BayK8644 increased the number of astrocytes exhibiting [Ca2+]i oscillations, and prolonged the responses to mGluR activation, indicating a possible effect on store-operated Ca2+ entry. Increasing [Ca2+]o increased the number of spontaneously active astrocytes and the number of transients exhibited by each astrocyte. Inhibition of the endoplasmic reticulum Ca2+ ATPase by cyclopiazonic acid also induced [Ca2+]i transients in astrocytes indicating a role for cytoplasmic Ca2+ in the induction of spontaneous oscillations. Incubation with 20����M Fluo-4 reduced the number of astrocytes exhibiting spontaneous increases. This study indicates that Ca2+ has a role in triggering Ca2+ release from an inositol 1,4,5,-triphosphate sensitive store in astrocytes during the generation of spontaneous [Ca2+]i oscillations

Nearwork-induced transient myopia in preadolescent Hong Kong Chinese

PURPOSE. To compare the magnitude and time course of nearwork-induced transient myopia (NITM) in preadolescent Hong Kong Chinese myopes and emmetropes. METHOD. Forty-five Hong Kong Chinese children, 35 myopes and 10 emmetropes aged 6 to 12 years (median, 7.5), monocularly viewed a letter target through a Badal lens for 5 minutes at either 5.00- or 2.50-D accommodative demand, followed by 3 minutes of viewing the equivalent target at optical infinity. Accommodative responses were measured continuously with a modified, infrared, objective open-field autorefractor. Accommodative responses were also measured for a countercondition: viewing of a letter target for 5 minutes at optical infinity, followed by 3 minutes of viewing the target at a 5.00-D accommodative demand. The results were compared with tonic accommodation and both subject and family history of refractive error. RESULTS. Retinal-blur-driven NITM was significantly greater in Hong Kong Chinese children with myopic vision than in the emmetropes after both near tasks, but showed no significant dose effect. The NITM was still evident 3 minutes after viewing the 5.00-D near task for 5 minutes. The magnitude of NITM correlated with the accommodative drift after viewing a distant target for more than 4 minutes, but was unrelated to the subjects' or family history of refractive error. CONCLUSIONS. In a preadolescent ethnic population with known predisposition to myopia, there is a significant posttask blur-driven accommodative NITM, which is sustained for longer than has previously been found in white adults.

Transient response in high-resolution Brillouin-based distributed sensing using probe pulses shorter than the acoustic relaxation time

We perform numerical simulations on a model describing a Brillouin-based temperature and strain sensor, testing its response when it is probed with relatively short pulses. Experimental results were recently published [e.g., Opt. Lett. 24, 510 (1999)] that showed a broadening of the Brillouin loss curve when the probe pulse duration is reduced, followed by a sudden and rather surprising reduction of the linewidth when the pulse duration gets shorter than the acoustic relaxation time. Our study reveals the processes responsible for this behavior. We give a clear physical insight into the problem, allowing us to define the best experimental conditions required for one to take the advantage of this effect.

Transient reconfigurable subangstrom-precise photonic circuits at the optical fiber surface

Transient fully reconfigurable photonic circuits can be introduced at the optical fiber surface with subangstrom precision. A building block of these circuits - a 0.7���-precise nano-bottle resonator - is experimentally created by local heating, translated, and annihilated.

Theoretical investigations of intercellular communication in the microcirculation: Conducted responses, myoendothelial projections and endothelium derived hyperpolarizing factor

The contractile state of microcirculatory vessels is a major determinant of the blood pressure of the whole systemic circulation. Continuous bi-directional communication exists between the endothelial cells (ECs) and smooth muscle cells (SMCs) that regulates calcium (Ca2+) dynamics in these cells. This study presents theoretical approaches to understand some of the important and currently unresolved microcirculatory phenomena. ^ Agonist induced events at local sites have been shown to spread long distances in the microcirculation. We have developed a multicellular computational model by integrating detailed single EC and SMC models with gap junction and nitric oxide (NO) coupling to understand the mechanisms behind this effect. Simulations suggest that spreading vasodilation mainly occurs through Ca 2+ independent passive conduction of hyperpolarization in RMAs. Model predicts a superior role for intercellular diffusion of inositol (1,4,5)-trisphosphate (IP3) than Ca2+ in modulating the spreading response. ^ Endothelial derived signals are initiated even during vasoconstriction of stimulated SMCs by the movement of Ca2+ and/or IP3 into the EC which provide hyperpolarizing feedback to SMCs to counter the ongoing constriction. Myoendothelial projections (MPs) present in the ECs have been recently proposed to play a role in myoendothelial feedback. We have developed two models using compartmental and 2D finite element methods to examine the role of these MPs by adding a sub compartment in the EC to simulate MP with localization of intermediate conductance calcium activated potassium channels (IKCa) and IP3 receptors (IP 3R). Both models predicted IP3 mediated high Ca2+ gradients in the MP after SMC stimulation with limited global spread. This Ca 2+ transient generated a hyperpolarizing feedback of ��� 2���3mV. ^ Endothelium derived hyperpolarizing factor (EDHF) is the dominant form of endothelial control of SMC constriction in the microcirculation. A number of factors have been proposed for the role of EDHF but no single pathway is agreed upon. We have examined the potential of myoendothelial gap junctions (MEGJs) and potassium (K+) accumulation as EDHF using two models (compartmental and 2D finite element). An extra compartment is added in SMC to simulate micro domains (MD) which have NaK��2 isoform sodium potassium pumps. Simulations predict that MEGJ coupling is much stronger in producing EDHF than alone K+ accumulation. On the contrary, K+ accumulation can alter other important parameters (EC V m, IKCa current) and inhibit its own release as well as EDHF conduction via MEGJs. The models developed in this study are essential building blocks for future models and provide important insights to the current understanding of myoendothelial feedback and EDHF.^

Effect of arginine and oscillatory calcium ion (II) on vascular response mediated via nitric oxide signaling in normal and salt sensitive hypertensive rat mesenteric arterioles

Hypertension, a major risk factor in the cardiovascular system, is characterized by an increase in the arterial blood pressure. High dietary sodium is linked to multiple cardiovascular disorders including hypertension. Salt sensitivity, a measure of how the blood pressure responds to salt intake is observed in more than 50% of the hypertension cases. Nitric Oxide (NO), as an endogenous vasodilator serves many important biological roles in the cardiovascular physiology including blood pressure regulation. The physiological concentrations for NO bioactivity are reported to be in 0-500 nM range. Notably, the vascular response to NO is highly regulated within a small concentration spectrum. Hence, much uncertainty surrounds how NO modulates diverse signaling mechanisms to initiate vascular relaxation and alleviate hypertension. Regulating the availability of NO in the vasculature has demonstrated vasoprotective effects. In addition, modulating the NO release by different means has proved to restore endothelial function. In this study we addressed parameters that regulated NO release in the vasculature, in physiology and pathophysiology such as salt sensitive hypertension. We showed that, in the rat mesenteric arterioles, Ca2+ induced rapid relaxation (time constants 20.8 �� 2.2 sec) followed with a much slower constriction after subsequent removal of the stimulus (time constants 104.8 �� 10.0 sec). An interesting observation was that a fourfold increase in the Ca 2+ frequency improved the efficacy of arteriolar relaxation by 61.1%. Our results suggested that, Ca2+ frequency-dependent transient release of NO from the endothelium carried encoded information; which could be translated into different steady state vascular tone. Further, Agmatine, a metabolite of L-arginine, as a ligand, was observed to relax the mesenteric arterioles. These relaxations were NO-dependent and occurred via &agr;-2 receptor activity. The observed potency of agmatine (EC50, 138.7 �� 12.1 �� ��M; n=22), was 40 fold higher than L-arginine itself (EC50, 18.3 �� 1.3 mM; n = 5). This suggested us to propose alternative parallel mechanism for L-arginine mediated vascular relaxation via arginine decarboxylase activity. In addition, the biomechanics of rat mesentery is important in regulation of vascular tone. We developed 2D finite element models that described the vascular mechanics of rat mesentery. With an inverse estimation approach, we identified the elasticity parameters characterizing alterations in normotensive and hypertensive Dahl rats. Our efforts were towards guiding current studies that optimized cardiovascular intervention and assisted in the development of new therapeutic strategies. These observations may have significant implications towards alternatives to present methods for NO delivery as a therapeutic target. Our work shall prove to be beneficial in assisting the delivery of NO in the vasculature thus minimizing the cardiovascular risk in handling abnormalities, such as hypertension.

Theoretical Investigation of Intra- and Inter-cellular Spatiotemporal Calcium Patterns in Microcirculation

Microcirculatory vessels are lined by endothelial cells (ECs) which are surrounded by a single or multiple layer of smooth muscle cells (SMCs). Spontaneous and agonist induced spatiotemporal calcium (Ca2+) events are generated in ECs and SMCs, and regulated by complex bi-directional signaling between the two layers which ultimately determines the vessel tone. The contractile state of microcirculatory vessels is an important factor in the determination of vascular resistance, blood flow and blood pressure. This dissertation presents theoretical insights into some of the important and currently unresolved phenomena in microvascular tone regulation. Compartmental and continuum models of isolated EC and SMC, coupled EC-SMC and a multi-cellular vessel segment with deterministic and stochastic descriptions of the cellular components were developed, and the intra- and inter-cellular spatiotemporal Ca2+ mobilization was examined. Coupled EC-SMC model simulations captured the experimentally observed localized subcellular EC Ca2+ events arising from the opening of EC transient receptor vanilloid 4 (TRPV4) channels and inositol triphosphate receptors (IP3Rs). These localized EC Ca2+ events result in endothelium-derived hyperpolarization (EDH) and Nitric Oxide (NO) production which transmit to the adjacent SMCs to ultimately result in vasodilation. The model examined the effect of heterogeneous distribution of cellular components and channel gating kinetics in determination of the amplitude and spread of the Ca2+ events. The simulations suggested the necessity of co-localization of certain cellular components for modulation of EDH and NO responses. Isolated EC and SMC models captured intracellular Ca2+ wave like activity and predicted the necessity of non-uniform distribution of cellular components for the generation of Ca2+ waves. The simulations also suggested the role of membrane potential dynamics in regulating Ca2+ wave velocity. The multi-cellular vessel segment model examined the underlying mechanisms for the intercellular synchronization of spontaneous oscillatory Ca2+ waves in individual SMC. From local subcellular events to integrated macro-scale behavior at the vessel level, the developed multi-scale models captured basic features of vascular Ca2+ signaling and provide insights for their physiological relevance. The models provide a theoretical framework for assisting investigations on the regulation of vascular tone in health and disease.

Temperature-related differences in the calcium transient between Atlantic cod (Gadus morhua) and steelhead trout (Oncorhynchus mykiss) cardiomyocytes

The Atlantic cod, Gadus morhua, differs from many teleosts in that its heart does not respond to adrenergic stimulation, and is more capable of maintaining function during acute temperature changes. To examine if differences in intracellular calcium mobilization are associated with these atypical responses, confocal microscopy was used to study the calcium handling of cardiac cells from Atlantic cod vs. steelhead trout at their acclimation temperature (10��C), or subjected to acute temperature changes (to 4 and 16��C), while being stimulated across a range of frequencies (10 ��� 110 min�����). In addition, cells were tested with and without tonic (10 nM) levels of adrenaline at 10��C, and pharmacological blockers were used to study the relative contributions of the L-type Ca����� channel, sarcoplasmic reticulum and Na+/Ca����� exchanger to the Ca����� transient. Consistent with previous in vitro and in situ studies, there were few significant effects of adrenaline on the Ca����� transient of cod cardiomyocytes, yet adrenaline had significant positive inotropic effects on trout cardiomyocytes. At 10��C, peak Ca����� (F/F���) only differed between the two species at low stimulation frequencies (10, 30 min-1), with trout F/F��� 25-35% higher. In contrast, the time to peak Ca����� and the time to half relaxation were both shorter (by 10 ��� 35% across frequencies) in cod. Acute temperature changes caused a shift in the Ca����� - frequency relationship in both species, with F/F��� values higher for trout at low frequencies (< 70 min�����) at 4��C, whereas this parameter was greater at all frequencies except 10 min����� in cod at 16��C. Unfortunately, these experiments did not highlight clear species differences in the relative contributions of the L-type Ca����� channels, sarcoplasmic reticulum and Na+/Ca����� exchange to the Ca����� transient.

Survivability : A Unifiying Concept for the Transient Resilience of Deterministic Dynamical Systems

16 pages

Survivability : A Unifiying Concept for the Transient Resilience of Deterministic Dynamical Systems

16 pages

Transient Receptor Potential Vanilloid 4 Ion Channel Functions as a Pruriceptor in Epidermal Keratinocytes to Evoke Histaminergic Itch.

TRPV4 ion channels function in epidermal keratinocytes and in innervating sensory neurons; however, the contribution of the channel in either cell to neurosensory function remains to be elucidated. We recently reported TRPV4 as a critical component of the keratinocyte machinery that responds to ultraviolet B (UVB) and functions critically to convert the keratinocyte into a pain-generator cell after excess UVB exposure. One key mechanism in keratinocytes was increased expression and secretion of endothelin-1, which is also a known pruritogen. Here we address the question of whether TRPV4 in skin keratinocytes functions in itch, as a particular form of "forefront" signaling in non-neural cells. Our results support this novel concept based on attenuated scratching behavior in response to histaminergic (histamine, compound 48/80, endothelin-1), not non-histaminergic (chloroquine) pruritogens in Trpv4 keratinocyte-specific and inducible knock-out mice. We demonstrate that keratinocytes rely on TRPV4 for calcium influx in response to histaminergic pruritogens. TRPV4 activation in keratinocytes evokes phosphorylation of mitogen-activated protein kinase, ERK, for histaminergic pruritogens. This finding is relevant because we observed robust anti-pruritic effects with topical applications of selective inhibitors for TRPV4 and also for MEK, the kinase upstream of ERK, suggesting that calcium influx via TRPV4 in keratinocytes leads to ERK-phosphorylation, which in turn rapidly converts the keratinocyte into an organismal itch-generator cell. In support of this concept we found that scratching behavior, evoked by direct intradermal activation of TRPV4, was critically dependent on TRPV4 expression in keratinocytes. Thus, TRPV4 functions as a pruriceptor-TRP in skin keratinocytes in histaminergic itch, a novel basic concept with translational-medical relevance.