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Deactivation
Kinds of Deactivation Terms modified by Deactivation Selected AbstractsAsymmetric Activation/Deactivation of Racemic Ru Catalysts for Highly Enantioselective Hydrogenation Irrespective of Ketonic Substrates: Molecular Design of Dimethylbinaphthylamine for Enantiomeric Catalysts DiscriminationADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 1-2 2003Koichi Mikami Abstract Asymmetric activation and deactivation of racemic catalysts are two extremes in asymmetric catalysis. In a combination of these two protocols, higher enantioselectivity can be achieved by maximizing the difference in catalytic activity between the enantiomers of racemic catalysts through selective activation and deactivation of enantiomeric catalysts. 3,3,-Dimethyl-2,2,-diamino-1,1,-binaphthyl (DM-DABN) is thus designed as a chiral poison (deactivator) for complete enantiomer resolution of racemic BINAP-Ru(II) catalysts. The catalyst system of DM-DABN, 1,2-diphenylethylenediamine (DPEN), and racemic BINAP-Ru(II) led to great success in highly enantioselective hydrogenation irrespective of the ketonic substrates. The lower catalytic activity of the BINAP-Ru(II)/DM-DABN complex stems from the electron delocalization from the Ru center to the diamine moiety in contrast to the BINAP-Ru(II)/DPEN complex where the highest electron densities are localized on the Ru-N region. The present ,asymmetric activation/deactivation protocol' can provide a guiding principle for the rational design of a molecule for enantiomeric discrimination between racemic catalysts. [source] Virtual Lesions Examining Cortical Function with Reversible DeactivationEUROPEAN JOURNAL OF NEUROLOGY, Issue 1 2003K. A. Jellinger No abstract is available for this article. [source] Unusual Deactivation in the Asymmetric Hydrogenation of Itaconic AcidADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 5 2009Thomas Schmidt Abstract During the asymmetric hydrogenation of itaconic acid with rhodium solvate complexes of the type [Rh(PP)(MeOH)2] BF4 (PP=DIPAMP, Me-DuPHOS) a deactivation with increasing substrate concentration is observed. It is shown that this inhibition phenomenon is due to the in situ formation of an inactive rhodium(III)-alkyl complex. Two crystal structures of single crystals of the responsible complexes (1) and (2) support the deactivation pathway. [source] Ascorbate Enhances Photogeneration of Hydrogen Peroxide Mediated by the Iris Melanin,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 3 2008Albert R. Wielgus The iris in the human eye is exposed to UV and visible light transmitted by the cornea. This pigmented tissue is bathed with the aqueous humor (AqH), which contains high concentration of ascorbate. It has been postulated that the presence of ascorbate in AqH can contribute to increased photoproduction of H2O2 mediated by the iris melanin. In this study, we monitored generation of H2O2 induced by UV,VIS irradiation of bovine irides, bovine and human iris homogenates and iris melanin. Our data show that exogenous ascorbate significantly amplified the rate of H2O2 photoformation in all melanotic samples. Deactivation of endogenous catalase with NaN3 in bovine irides increased the level of the accumulated H2O2 in the bathing solution following sample irradiation. Photoformation of H2O2 in samples with exogenous ascorbate was accompanied by its photo-oxidation. Both photoprocesses exhibited significant wavelength dependence. EPR spectroscopy measurements showed that ascorbyl radical is an intermediate product of the ascorbate photo-oxidation. The photoproduction of H2O2 and photo-oxidation of ascorbate appear to be stoichiometric processes. No significant differences in the photoreactivity of iridial melanin from donors of different age and iris color was found. We postulate that also in vivo ascorbate increases the rate of iris melanin-mediated photoformation of H2O2 and its steady state concentration in AqH. [source] Deactivation of the boron,oxygen recombination center in silicon by illumination at elevated temperaturePHYSICA STATUS SOLIDI - RAPID RESEARCH LETTERS, Issue 3 2008Bianca Lim Abstract The boron,oxygen-related recombination center responsible for the light-induced degradation of solar cells made on boron-doped oxygen-contaminated silicon is deactivated by simultaneously annealing the silicon wafer in the temperature range 135,210 °C and illuminating it with white light. The recombination lifetime after deactivation is found to be stable under illumination at room temperature. The deactivation process is shown to be thermally activated with an activation energy of 0.7 eV. Based on the experimental findings, a defect reaction model is proposed explaining the deactivation of the boron,oxygen center. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] The evolutionarily conserved residue A653 plays a key role in HERG channel closingTHE JOURNAL OF PHYSIOLOGY, Issue 11 2009Svetlana Z. Stepanovic Human ether-a-go-go- related gene (HERG) encodes the rapid, outwardly rectifying K+ current IKr that is critical for repolarization of the cardiac action potential. Congenital HERG mutations or unintended pharmaceutical block of IKr can lead to life-threatening arrhythmias. Here, we assess the functional role of the alanine at position 653 (HERG-A653) that is highly conserved among evolutionarily divergent K+ channels. HERG-A653 is close to the ,glycine hinge' implicated in K+ channel opening, and is flanked by tyrosine 652 and phenylalanine 656, which contribute to the drug binding site. We substituted an array of seven (I, C, S, G, Y, V and T) amino acids at position 653 and expressed individual variants in heterologous systems to assess changes in gating and drug binding. Substitution of A653 resulted in negative shifts of the V1/2 of activation ranging from ,23.6 (A653S) to ,62.5 (A653V) compared to ,11.2 mV for wild-type (WT). Deactivation was also drastically altered: channels with A653I/C substitutions exhibited delayed deactivation in response to test potentials above the activation threshold, while A653S/G/Y/V/T failed to deactivate under those conditions and required hyperpolarization and prolonged holding potentials at ,130 mV. While A653S/G/T/Y variants showed decreased sensitivity to the IKr inhibitor dofetilide, these changes could not be correlated with defects in channel closure. Homology modelling suggests that in the closed state, A653 forms tight contacts with several residues from the neighbouring subunit in the tetramer, playing a key role in S6 helix packing at the narrowest part of the vestibule. Our study suggests that A653 plays an important functional role in the outwardly rectifying gating behaviour of HERG, supporting channel closure at membrane potentials negative to the channel activation threshold. [source] ORIGINAL RESEARCH: Phosphodiesterase Type 5 Regulation in the Penile Corpora CavernosaTHE JOURNAL OF SEXUAL MEDICINE, Issue S3 2009Ching-Shwun Lin PhD ABSTRACT Introduction., Penile detumescence depends on the hydrolysis of cyclic guanosine monophosphate (cGMP) by phosphodiesterase type 5 (PDE5). It is hoped that a review of publications relevant to the regulation of PDE5 in the penis will be helpful to both scientists and clinicians who are interested in the sciences of erectile function/dysfunction. Aims., The aim of this article is to comprehensively review the mechanisms by which PDE5 activity and expression in the penis are regulated. All published studies relevant to PDE5 regulation in the penis or penile cells will be reviewed. Methods., Entrez (PubMed) was used to search for publications relevant to the topics of this review. Keywords used in the searches included vascular, cavernous, penis, smooth muscle, signaling molecules, erection, priapism, and PDE5. Articles that are dedicated to the study of erectile function/dysfunction were prioritized for citation. Results., Regulation of PDE5 can occur at both protein and gene levels. At protein level, PDE5 is activated by phosphorylation and/or allosteric cGMP binding. Deactivation is carried out by protein phosphatase 1 and thus linked to the Rho-kinase signaling pathway. Cleavage of PDE5 into an inactive form has been shown as carried out by caspase-3. At the gene level, PDE5 expression is regulated at two alternative promoters, PDE5A and PDE5A2, both of which are positively regulated by cyclic adenosine monophosphate and cGMP. Downregulation of PDE5 has been observed in the penis of castrated animals; however, proof of androgen regulation of PDE5 gene requires examination of the smooth muscle content. Hyperoxia and hypoxia, respectively, regulate PDE5 expression positively and negatively. Hypoxic downregulation of PDE5 is a possible mechanism for the development of priapism. Conclusions., PDE5 can be regulated at protein and gene levels. In the penis, changes of PDE5 activity have been linked to its phosphorylation status, and downregulation of PDE5 expression has been associated with hypoxia. Lin CS. PDE5 regulation in the penile corpora nervosa. J Sex Med 2009;6(suppl 3):203,209. [source] High-temperature sequestration of elemental mercury by noncarbon based sorbentsASIA-PACIFIC JOURNAL OF CHEMICAL ENGINEERING, Issue 2 2010Sung Jun Lee Abstract This work is concerned with sequestration of elemental Hg at high temperatures (900,1100 °C) on a sorbent that is mineral based, rather than carbon based. This sorbent consists of an intimate mixture of CaO, CaCO3, and Al2O3,2SiO2, and is manufactured in industrially relevant quantities (metric tons) from residues produced in paper recycling processes. In contrast to activated carbon (AC), this noncarbon based sorbent has special advantages in that, it can actually enhance fly ash utilization for cement manufacture, rather than diminish it, as is the case for AC. Disperse phase experiments have been conducted, using an externally heated quartz tube reactor, with sorbent feeding rates ranging from 1 to 6 g/h. Preliminary results indicate that Hg removal efficiency is sensitive to sorbent feed rates and to furnace temperature. The Hg removal percentage increased with both these variables. Two mechanisms come into play: an in-flight Hg sorption mechanism, and an Hg sorption mechanism related to sorbent deposits on the reactor wall. A maximum total (in-flight plus deposit-related) Hg removal efficiency of 83,90% was obtained at temperatures of 900,1100 °C. There was negligible sorption by either mechanism at temperatures below 600 °C. Results for the in-flight mechanism alone showed a maximum sorption efficiency at ,900 °C, whereas that on the reactor surface increased monotonically with temperature. This suggests that sorbent deactivation can occur in-flight at high temperatures, which is in agreement with other fixed bed results obtained in this laboratory. Deactivation was not apparent for the sorbent-related substance formed on the reactor wall. Raw and spent sorbents were analyzed by X-ray diffraction (XRD) and scanning electron microscopy with energy dispersive spectrophotometer (SEM-EDS) to identify the sorbent mineral transitions that seem to activate the process. The in-flight mechanisms appear to involve (1) activation of the sorbent, caused most probably by an internal solid,solid reaction, followed by (2) Hg sorption, and (3) possible deactivation, if the temperatures are too high for longer period. Reactor surface mechanisms still remain to be elucidated. Copyright © 2009 Curtin University of Technology and John Wiley & Sons, Ltd. [source] Deactivation of Formate Dehydrogenase (FDH) in Solution and at Gas-Liquid InterfacesBIOTECHNOLOGY PROGRESS, Issue 6 2005Andreas S. Bommarius Enzymes, increasingly important in the synthesis of fine chemicals and pharmaceutical intermediates, are often insufficiently stable under reacting conditions. We have investigated the stability, in homogeneous aqueous solution and at gas-liquid interfaces, of formate dehydrogenase (FDH), important for cofactor regeneration, from Candida boidinii and overexpressed in E. coli. When exposed to mechanical stress, residual activity, [E]t/[E]0, and residual protein were found to scale proportionally with gas-liquid surface area in the bubble column, verifying a surface-driven process, and with time and total throughput in a gear pump, but did not seem to be influenced much by shear in a Couette viscometer. All FDH variants are deactivated by chaotropes but not kosmotropes: the first-order deactivation constant kd correlates well with the Jones-Dole coefficient B but not well with the surface tension increment ,, of various concentrated ammonium salt solutions. This finding might provide guidance for focusing the search for quantitative theories of Hofmeister effects. [source] Shear Deactivation of Cellulase, Exoglucanase, Endoglucanase, and ,-Glucosidase in a Mechanically Agitated ReactorBIOTECHNOLOGY PROGRESS, Issue 6 2001Tejas P. Gunjikar Shear deactivation of cellulase and its major component enzymes, viz., exoglucanase (exo -1,4-,- D -glucan-4-cellobiohydrolase), endoglucanase (endo -1,4-,- D -glucanhydrolase), and 1,4-,-glucosidase, was carried out by exposing cellulase to shear in a mechanically agitated reactor in the presence as well as in the absence of the substrate cellulose. Cellulase was found to undergo deactivation when subjected to shear, and the extent of deactivation increased with increasing speed of agitation. Among the three major component enzymes of cellulase, exoglucanase showed rapid deactivation and contributed the most to cellulase deactivation. The presence of a substrate did not affect the deactivation of cellulase. [source] Production of Hydrogen from Dimethyl Ether over Supported Rhodium CatalystsCHEMCATCHEM, Issue 2 2009Gyula Halasi Abstract Infrared (IR) spectroscopy revealed that dimethyl ether (DME) undergoes partial dissociation on pure and rhodium-containing CeO2 at 300,K to yield methoxy and methyl species. This process is promoted by the presence of rhodium. By means of thermal desorption measurements (TPD), the adsorption of DME on Rh/CeO2 at 300,K and subsequent decomposition of DME (Tp,370,K), releasing H2, CO, CO2, and CH4, with Tp between 420 and 673,K, were ascertained. Rh/CeO2 is an effective catalyst for the decomposition of DME to give H2 (29,35,%), CO (27,30,%) and CH4 (32,38,%) as major products with complete conversion at 673,723,K. Adding water to DME changed the product distribution and increased the selectivity of H2 formation from 30,35,% to 58,% at 723,K. In,situ IR spectroscopy showed absorption bands of CO at 2034 and 1893,cm,1 during the reaction at 673,773,K. Deactivation of the catalyst did not occur at 773,K during the time measured (approximately 10 h). Rh deposited on carbon Norit also exhibited a high activity towards the decomposition of DME, but the selectivity towards hydrogen was lower. [source] Model-Aided Design of a Three-Phase Gas-Lift Reactor for Oxidation Accompanied by Catalyst Reversible DeactivationCHEMICAL ENGINEERING & TECHNOLOGY (CET), Issue 12 2009Z. Gogová Abstract A mathematical model of a three-phase gas-lift reactor (GLR) is developed to aid the design of a target reactor for simultaneous substrate catalytic oxidation in riser and a deactivated reactivation catalyst in the downcomer section of the multifunctional reactor. In the GLR model, the hydrodynamics of a real GLR and the kinetics of glucose oxidation by air over a palladium catalyst are incorporated. The GLR model searches for the optimal geometry of the target reactor. With regard to the GLR optimal geometry, the reactor productivity is maximal for given input operational conditions. An algorithm of the GLR model is presented together with simulation results of the target GLR and with insight into the parametric sensitivity of the model. Effects of the reaction components concentrations and the gas-phase superficial velocity on the location of the target reactor optimal geometry and on the reactor productivity are discussed. [source] A Novel Radial-Flow, Spherical-Bed Reactor Concept for Methanol Synthesis in the Presence of Catalyst DeactivationCHEMICAL ENGINEERING & TECHNOLOGY (CET), Issue 11 2008R. Rahimpour Abstract A radial-flow, spherical-bed reactor concept for methanol synthesis in the presence of catalyst deactivation, has been proposed. This reactor configuration visualizes the concentration and temperature distribution inside a radial-flow packed bed with a novel design for improving reactor performance with lower pressure drop. The dynamic simulation of spherical multi-stage reactors has been studied in the presence of long-term catalyst deactivation. Model equations were solved by the orthogonal collocation method. The performance of the spherical multi-stage reactors was compared with a conventional single-type tubular reactor. The results show that for this case study and with similar reactor specifications and operating conditions, the two-stage spherical reactor is better than other alternatives such as single-stage spherical, three-stage spherical and conventional tubular reactors. By increasing the number of stages of a spherical reactor, one increases the quality of production and decreases the quantity of production. [source] Incorporation of Dynamic Flexibility in the Design of a Methanol Synthesis Loop in the Presence of Catalyst DeactivationCHEMICAL ENGINEERING & TECHNOLOGY (CET), Issue 1 2008P. Parvasi Abstract A typical methanol loop reactor is analyzed in this study. All basic equipment in the Lurgi-type methanol loop is included in the proposed model. A detailed dynamic model described by a set of ordinary differential and algebraic equations is developed to predict the behavior of the overall process. The model is validated against plant data. A new deactivation model is proposed and its parameters are estimated using daily plant data. The interesting feature of this model is that it incorporates the effect of carbon dioxide and carbon monoxide on the catalyst deactivation. Using the model, the effect of various factors to compensate for the reduction of production rate due to catalyst deactivation has been examined. Some improvements can be achieved by adjusting the operating conditions. Finally, a strategy is proposed for prevention of reduced production due to catalyst deactivation. [source] Incorporation of Flexibility in the Design of a Methanol Synthesis Loop in the Presence of Catalyst DeactivationCHEMICAL ENGINEERING & TECHNOLOGY (CET), Issue 6 2003M.R. Rahimpour Abstract This paper presents the incorporation of process flexibility into a methanol synthesis loop operating under catalyst deactivation. A design methodology is discussed with regard to catalyst deactivation, and some limitations are identified. In the current flexibility study the size of the reactor and recycle ratio have been fixed. Attempts to maintain methanol production at the rates observed with fresh catalyst included increased pressure, increased make up gas flow rate, and the injection of carbon dioxide into the make up gas at optimized inlet temperature. In order to provide flexibility and produce a design compatible with increased production rates, the effect of interrelating equipment had to be considered. As a result of catalyst deactivation, an increased flow rate is necessary and the altered process streams entering the preheater disturb the reactor inlet temperature. These issues should be considered in the design stage and may be resolved by the flexible designs presented. [source] Evaluation of epileptogenic networks in children with tuberous sclerosis complex using EEG-fMRIEPILEPSIA, Issue 5 2008Julia Jacobs Summary Purpose: Ninety percent of patients with tuberous sclerosis complex (TSC) have epilepsy. Identification of epileptogenic areas can be difficult and studies are needed to characterize the epileptogenic network in more detail. Methods: Five children with TSC and focal epilepsy were studied using simultaneous EEG and functional MRI recordings. Tubers were marked by a neuroradiologist on the anatomical MRI. Spike-associated BOLD (blood oxygenation level-dependent) responses were superimposed with lesions. Results: Thirteen different types of interictal epileptiform discharges (IED) were analyzed with 12 showing a BOLD response, all involving more than one tuber. Five studies had tubers with activations exclusively within the lesion, three studies had lesional activations extending to perilesional areas, and two studies had activations involving exclusively perilesional areas of at least one tuber. Deactivations exclusively within a tuber were found in six studies, lesional deactivations extending to perilesional areas were found in four studies, and tubers with exclusively perilesional deactivations were found in five studies. A BOLD response was found in at least one tuber in the lobe of IED generation and presumed seizure onset (according to telemetry) in all patients. In four patients, the same tubers were involved following different IED localizations. The observed changes were always multifocal, sometimes involving tubers distant from the IED field. Discussion: These findings suggest extended epileptogenic networks in patients with TSC, which exceed networks described in PET and SPECT studies. It was possible to identify specific interictally active tubers. EEG-fMRI provides a noninvasive method to select tubers and areas at their borders for further presurgical investigations. [source] Noninvasive dynamic imaging of seizures in epileptic patientsHUMAN BRAIN MAPPING, Issue 12 2009Louise Tyvaert Abstract Epileptic seizures are due to abnormal synchronized neuronal discharges. Techniques measuring electrical changes are commonly used to analyze seizures. Neuronal activity can be also defined by concomitant hemodynamic and metabolic changes. Simultaneous electroencephalogram (EEG)-functional MRI (fMRI) measures noninvasively with a high-spatial resolution BOLD changes during seizures in the whole brain. Until now, only a static image representing the whole seizure was provided. We report in 10 focal epilepsy patients a new approach to dynamic imaging of seizures including the BOLD time course of seizures and the identification of brain structures involved in seizure onset and discharge propagation. The first activation was observed in agreement with the expected location of the focus based on clinical and EEG data (three intracranial recordings), thus providing validity to this approach. The BOLD signal preceded ictal EEG changes in two cases. EEG-fMRI may detect changes in smaller and deeper structures than scalp EEG, which can only record activity form superficial cortical areas. This method allowed us to demonstrate that seizure onset zone was limited to one structure, thus supporting the concept of epileptic focus, but that a complex neuronal network was involved during propagation. Deactivations were also found during seizures, usually appearing after the first activation in areas close or distant to the activated regions. Deactivations may correspond to actively inhibited regions or to functional disconnection from normally active regions. This new noninvasive approach should open the study of seizure generation and propagation mechanisms in the whole brain to groups of patients with focal epilepsies. Hum Brain Mapp, 2009. © 2009 Wiley-Liss, Inc. [source] Negative BOLD responses to epileptic spikesHUMAN BRAIN MAPPING, Issue 6 2006Eliane Kobayashi Abstract Simultaneous electroencephalogram/functional magnetic resonance imaging (EEG-fMRI) during interictal epileptiform discharges can result in positive (activation) and negative (deactivation) changes in the blood oxygenation level-dependent (BOLD) signal. Activation probably reflects increased neuronal activity and energy demand, but deactivation is more difficult to explain. Our objective was to evaluate the occurrence and significance of deactivations related to epileptiform discharges in epilepsy. We reviewed all EEG-fMRI studies from our database, identified those with robust responses (P = 0.01, with ,5 contiguous voxels with a |t| > 3.1, including ,1 voxel at |t| > 5.0), and divided them into three groups: activation (A = 8), deactivation (D = 9), and both responses (AD = 43). We correlated responses with discharge type and location and evaluated their spatial relationship with regions involved in the "default" brain state (Raichle et al. [2001]: Proc Natl Acad Sci 98:676,682]. Deactivations were seen in 52/60 studies (AD+D): 26 related to focal discharges, 12 bilateral, and 14 generalized. Deactivations were usually distant from anatomical areas related to the discharges and more frequently related to polyspike- and spike-and-slow waves than to spikes. The "default" pattern occurred in 10/43 AD studies, often associated with bursts of generalized discharges. In conclusion, deactivations are frequent, mostly with concomitant activation, for focal and generalized discharges. Discharges followed by a slow wave are more likely to result in deactivation, suggesting neuronal inhibition as the underlying phenomenon. Involvement of the "default" areas, related to bursts of generalized discharges, provides evidence of a subclinical effect of the discharges, temporarily suspending normal brain function in the resting state. Hum Brain Mapp, 2005. © 2005 Wiley-Liss, Inc. [source] Fault-tolerant control of nonlinear processes: performance-based reconfiguration and robustnessINTERNATIONAL JOURNAL OF ROBUST AND NONLINEAR CONTROL, Issue 3 2006Prashant Mhaskar Abstract This work considers the problem of control system/actuator failures in nonlinear processes subject to input constraints and presents two approaches for fault-tolerant control that focus on incorporating performance and robustness considerations, respectively. In both approaches, first a family of candidate control configurations, characterized by different manipulated inputs, is identified for the process under consideration. Performance considerations are first incorporated via the design of a Lyapunov-based predictive controller that enforces closed-loop stability from an explicitly characterized set of initial conditions (computed using an auxiliary Lyapunov-based nonlinear controller). A hierarchical switching policy is derived, that uses stability considerations (evaluated via the presence of the state in the stability region of a control configuration) to ascertain the suitability of a candidate backup configuration and then performance considerations are again considered in choosing between the suitable backup configurations. Next, we consider the problem of implementing fault-tolerant control to nonlinear processes subject to input constraints and uncertainty. To this end, we first design a robust hybrid predictive controller for each candidate control configuration that guarantees stability from an explicitly characterized set of initial conditions, subject to uncertainty and constraints. A switching policy is then derived to orchestrate the activation/deactivation of the constituent control configurations. Finally, simulation studies are presented to demonstrate the implementation and evaluate the effectiveness of the proposed fault-tolerant control method. Copyright © 2005 John Wiley & Sons, Ltd. [source] Damped oscillations in the adaptive response of the iron homeostasis network of E. coliMOLECULAR MICROBIOLOGY, Issue 2 2010Amnon Amir Summary Living organisms often have to adapt to sudden environmental changes and reach homeostasis. To achieve adaptation, cells deploy motifs such as feedback in their genetic networks, endowing the cellular response with desirable properties. We studied the iron homeostasis network of E. coli, which employs feedback loops to regulate iron usage and uptake, while maintaining intracellular iron at non-toxic levels. Using fluorescence reporters for iron-dependent promoters in bulk and microfluidics-based, single-cell experiments, we show that E. coli cells exhibit damped oscillations in gene expression, following sudden reductions in external iron levels. The oscillations, lasting for several generations, are independent of position along the cell cycle. Experiments with mutants in network components demonstrate the involvement of iron uptake in the oscillations. Our findings suggest that the response is driven by intracellular iron oscillations large enough to induce nearly full network activation/deactivation. We propose a mathematical model based on a negative feedback loop closed by rapid iron uptake, and including iron usage and storage, which captures the main features of the observed behaviour. Taken together, our results shed light on the control of iron metabolism in bacteria and suggest that the oscillations represent a compromise between the requirements of stability and speed of response. [source] Baroreflex Sensitivity: Measurement and Clinical ImplicationsANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 2 2008Maria Teresa La Rovere M.D. Alterations of the baroreceptor-heart rate reflex (baroreflex sensitivity, BRS) contribute to the reciprocal reduction of parasympathetic activity and increase of sympathetic activity that accompany the development and progression of cardiovascular diseases. Therefore, the measurement of the baroreflex is a source of valuable information in the clinical management of cardiac disease patients, particularly in risk stratification. This article briefly recalls the pathophysiological background of baroreflex control, and reviews the most relevant methods that have been developed so far for the measurement of BRS. They include three "classic" methods: (i) the use of vasoactive drugs, particularly the ,-adrenoreceptor agonist phenylephrine, (ii) the Valsalva maneuver, which produces a natural challenge for the baroreceptors by voluntarily increasing intrathoracic and abdominal pressure through straining, and (iii) the neck chamber technique, which allows a selective activation/deactivation of carotid baroreceptors by application of a negative/positive pressure to the neck region. Two more recent methods based on the analysis of spontaneous oscillations of systolic arterial pressure and RR interval are also reviewed: (i) the sequence method, which analyzes the relationship between increasing/decreasing ramps of blood pressure and related increasing/decreasing changes in RR interval through linear regression, and (ii) spectral methods, which assess the relationship (in terms of gain) between specific oscillatory components of the two signals. The limitations of the coherence criterion for the computation of spectral BRS are discussed, and recent proposals for overcoming them are presented. Most relevant clinical applications of BRS measurement are finally reviewed with particular reference to patients with myocardial infarction and heart failure. [source] Optimization of Operating Temperature for Continuous Immobilized Glucose Isomerase Reactor with Pseudo Linear KineticsENGINEERING IN LIFE SCIENCES (ELECTRONIC), Issue 5 2004N.M. Faqir Abstract In this work, the optimal operating temperature for the enzymatic isomerization of glucose to fructose using a continuous immobilized glucose isomerase packed bed reactor is studied. This optimization problem describing the performance of such reactor is based on reversible pseudo linear kinetics and is expressed in terms of a recycle ratio. The thermal deactivation of the enzyme as well as the substrate protection during the reactor operation is considered. The formulation of the problem is expressed in terms of maximization of the productivity of fructose. This constrained nonlinear optimization problem is solved using the disjoint policy of the calculus of variations. Accordingly, this method of solution transforms the nonlinear optimization problem into a system of two coupled nonlinear ordinary differential equations (ODEs) of the initial value type, one equation for the operating temperature profile and the other one for the enzyme activity. The ODE for the operating temperature profile is dependent on the recycle ratio, operating time period, and the reactor residence time as well as the kinetics of the reaction and enzyme deactivation. The optimal initial operating temperature is selected by solving the ODEs system by maximizing the fructose productivity. This results into an unconstrained one-dimensional optimization problem with simple bounds on the operating temperature. Depending on the limits of the recycle ratio, which represents either a plug flow or a mixed flow reactor, it is found that the optimal temperature of operation is characterized by an increasing temperature profile. For higher residence time and low operating periods the residual enzyme activity in the mixed flow reactor is higher than that for the plug flow reactor, which in turn allows the mixed flow reactor to operate at lower temperature than that of the plug flow reactor. At long operating times and short residence time, the operating temperature profiles are almost the same for both reactors. This could be attributed to the effect of substrate protection on the enzyme stability, which is almost the same for both reactors. Improvement in the fructose productivity for both types of reactors is achieved when compared to the constant optimum temperature of operation. The improvement in the fructose productivity for the plug flow reactor is significant in comparison with the mixed flow reactor. [source] Coexistence of symptomatic focal and absence seizures: Video-EEG and EEG-fMRI evidence of overlapping but independent epileptogenic networksEPILEPSIA, Issue 7 2009Serge Chassagnon Summary The distinction between typical absences and hypomotor seizures in patients having frontal lesions is difficult. In focal epilepsy, generalized-like interictal discharges can reflect either a coexistent generalized epileptic trait or a secondary bilateral synchrony. Using combined measures of the EEG and blood oxygenation level dependent (BOLD) activity, we studied a 50-year-old patient with both absence-like and symptomatic focal motor seizures. Focal activity induced activation in the lesional area and deactivation in the contralateral central cortex. Generalized spike-and-wave discharges (GSWDs) resulted also in perilesional activation, and multifocal symmetrical cortical and thalamic activations, and deactivation in associative cortical areas. Although the central cortex was involved during both types of epileptic activity, electroencephalography (EEG),functional magnetic resonance imaging (fMRI) revealed distinct neuronal networks at the time of the focal or generalized discharges, allowing a clear-cut differentiation of the generators. Whether the patient had distinct epileptic syndromes or distinct electrographic patterns from the lesional trigger remains debatable. [source] A comparison of five fMRI protocols for mapping speech comprehension systemsEPILEPSIA, Issue 12 2008Jeffrey R. Binder Summary Aims:, Many fMRI protocols for localizing speech comprehension have been described, but there has been little quantitative comparison of these methods. We compared five such protocols in terms of areas activated, extent of activation, and lateralization. Methods:, fMRI BOLD signals were measured in 26 healthy adults during passive listening and active tasks using words and tones. Contrasts were designed to identify speech perception and semantic processing systems. Activation extent and lateralization were quantified by counting activated voxels in each hemisphere for each participant. Results:, Passive listening to words produced bilateral superior temporal activation. After controlling for prelinguistic auditory processing, only a small area in the left superior temporal sulcus responded selectively to speech. Active tasks engaged an extensive, bilateral attention, and executive processing network. Optimal results (consistent activation and strongly lateralized pattern) were obtained by contrasting an active semantic decision task with a tone decision task. There was striking similarity between the network of brain regions activated by the semantic task and the network of brain regions that showed task-induced deactivation, suggesting that semantic processing occurs during the resting state. Conclusions:, fMRI protocols for mapping speech comprehension systems differ dramatically in pattern, extent, and lateralization of activation. Brain regions involved in semantic processing were identified only when an active, nonlinguistic task was used as a baseline, supporting the notion that semantic processing occurs whenever attentional resources are not controlled. Identification of these lexical-semantic regions is particularly important for predicting language outcome in patients undergoing temporal lobe surgery. [source] IMAGING STUDY: Exposure to smoking cues during an emotion recognition task can modulate limbic fMRI activation in cigarette smokersADDICTION BIOLOGY, Issue 4 2009Eric Artiges ABSTRACT Smoking cues (SCs) refer to smoking-associated environmental stimuli that may trigger craving and withdrawal symptoms, and predispose to relapse in smokers. Although previous brain imaging studies have explored neural responses to SCs, no study has characterized the effects of SCs on cerebral activity in smokers engaged in an attention-demanding cognitive task that is unrelated to smoking. Thirteen tobacco smokers and a demographically matched group of 13 healthy non-smokers participated in a fast event-related functional magnetic resonance imaging (fMRI) study that involved a visual task integrating SCs and neutral cues (NCs) during emotion recognition trials requiring a high level of attention. No significant SC-induced alterations were detected in smokers' behavioural performance. fMRI results show that non-smokers exhibited no difference between SC and NC trials; in contrast, smokers showed SC-induced widespread deactivations in a limbic, paralimbic and striatal network classically involved in addiction, and activation in the right dorsolateral prefrontal cortex. In addition, a correlation between deactivation of the right insula and the severity of smoking dependence (Fagerström test) was detected in smokers. These results suggest that the neural reactivity of smokers to SCs can be modified in the context of a cognitive challenge. This could reflect smokers' ability to inhibit cue-induced craving and may help in smoking cessation. [source] Gold(I) Complexes of P,N Ligands and Their Catalytic ActivityEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 7 2010Chosu Khin Abstract Gold(I) complexes were readily prepared by reaction of the respective ligands with (Me2S)AuCl in CH2Cl2. Complexes of formula LAuCl {L = diphenyl(2-pyridyl)phosphane (PPh2Py), (R)-(+)-4-[(2)-(diphenylphosphanyl)-1-naphthyl]- N -[(R)-1-phenylethyl]-1-phthalazinamine (PINAP)} were obtained when a 1:1 molar ratio of ligand to starting gold precursor was used. When a 2:1 ratio of ligand to gold precursor was used with PPh2Py or MandyPhos as ligands, complexes of the type L2AuCl were obtained. All complexes were fully characterized, and single-crystal X-ray structures could be determined for four complexes. Chloride ions were removed by reaction with silver salts, such as AgNTf2, AgOTf and AgBF4, for the use of these complexes as catalysts. After the catalytic reaction with alkynes and alcohols in acetonitrile, a unique trinuclear gold(I) complex derived from [(PPh2Py)Au]BF4 could be characterized by X-ray structural analysis, showing a mode of catalyst deactivation. [source] Cortical control of thermoregulatory sympathetic activationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2010M. Fechir Abstract Thermoregulation enables adaptation to different ambient temperatures. A complex network of central autonomic centres may be involved. In contrast to the brainstem, the role of the cortex has not been clearly evaluated. This study was therefore designed to address cerebral function during a whole thermoregulatory cycle (cold, neutral and warm stimulation) using 18-fluordeoxyglucose-PET (FDG-PET). Sympathetic activation parameters were co-registered. Ten healthy male volunteers were examined three times on three different days in a water-perfused whole-body suit. After a baseline period (32°C), temperature was either decreased to 7°C (cold), increased to 50°C (warm) or kept constant (32°C, neutral), thereafter the PET examination was performed. Cerebral glucose metabolism was increased in infrapontine brainstem and cerebellar hemispheres during cooling and warming, each compared with neutral temperature. Simultaneously, FDG uptake decreased in the bilateral anterior/mid-cingulate cortex during warming, and in the right insula during cooling and warming. Conjunction analyses revealed that right insular deactivation and brainstem activation appeared both during cold and warm stimulation. Metabolic connectivity analyses revealed positive correlations between the cortical activations, and negative correlations between these cortical areas and brainstem/cerebellar regions. Heart rate changes negatively correlated with glucose metabolism in the anterior cingulate cortex and in the middle frontal gyrus/dorsolateral prefrontal cortex, and changes of sweating with glucose metabolism in the posterior cingulate cortex. In summary, these results suggest that the cerebral cortex exerts an inhibitory control on autonomic centres located in the brainstem or cerebellum. These findings may represent reasonable explanations for sympathetic hyperactivity, which occurs, for example, after hemispheric stroke. [source] Sensory gating in primary insomniaEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2010Ilana S. Hairston Abstract Although previous research indicates that sleep architecture is largely intact in primary insomnia (PI), the spectral content of the sleeping electroencephalographic trace and measures of brain metabolism suggest that individuals with PI are physiologically more aroused than good sleepers. Such observations imply that individuals with PI may not experience the full deactivation of sensory and cognitive processing, resulting in reduced filtering of external sensory information during sleep. To test this hypothesis, gating of sensory information during sleep was tested in participants with primary insomnia (n = 18) and good sleepers (n = 20). Sensory gating was operationally defined as (i) the difference in magnitude of evoked response potentials elicited by pairs of clicks presented during Wake and Stage II sleep, and (ii) the number of K complexes evoked by the same auditory stimulus. During wake the groups did not differ in magnitude of sensory gating. During sleep, sensory gating of the N350 component was attenuated and completely diminished in participants with insomnia. P450, which occurred only during sleep, was strongly gated in good sleepers, and less so in participants with insomnia. Additionally, participants with insomnia showed no stimulus-related increase in K complexes. Thus, PI is potentially associated with impaired capacity to filter out external sensory information, especially during sleep. The potential of using stimulus-evoked K complexes as a biomarker for primary insomnia is discussed. [source] Diversity of GABAA receptor synaptic currents on individual pyramidal cortical neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2007Timothy Ing Abstract Miniature GABAA receptor-mediated inhibitory postsynaptic currents (mIPSCs) in cortical pyramidal neurons have previously been categorized into two types: small amplitude mIPSCs with a mono-exponential deactivation (mono-mIPSCs) and relatively larger mIPSCs with bi-exponential deactivation (bi-mIPSCs). The aim of this study was to determine if the GABAA channels that underlie these mIPSCSs are molecularly distinct. We found, using non-stationary noise analysis, that the difference in their amplitude could be not accounted for by their single channel conductance (both were 40 pS). Next, using , subunit selective GABAA receptor modulators, we examined the identity of the , subunits that may be expressed in the synapses that give rise to these mIPSCs. Zolpidem (100 and 500 nm, ,1 selective) affected the deactivation of a subset of the mono-mIPSCs, indicating that ,1 subunits are not highly expressed in these synapses. However, zolpidem (100 nm) prolonged the deactivation of all bi-mIPSCs, indicating a high abundance of ,1 subunits in these synapses. SB-205384 (,3 selective) had no effect on the mono-mIPSCs but the bi-mIPSCs were prolonged. Furosemide (,4 selective) reduced the amplitude of only the mono-mIPSCs. L655,708 (,5 selective) reduced the amplitude of both populations and shortened the duration of the mono-mIPSCs. Finally, we found that the neuroactive steroid pregesterone sulphate reduced the amplitude of both mIPSC types. These results provide pharmacological evidence that synapses on cortical pyramidal neurons are molecularly distinct. The purpose of these different types of synapses may be to provide different inhibitory timing patterns on these cells. [source] Molecular analysis of the A322D mutation in the GABAA receptor ,1 -subunit causing juvenile myoclonic epilepsyEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2005Klaus Krampfl Abstract Juvenile myoclonic epilepsy (JME) belongs to the most common forms of hereditary epilepsy, the idiopathic generalized epilepsies. Although the mode of inheritance is usually complex, mutations in single genes have been shown to cause the disease in some families with autosomal dominant inheritance. The first mutation in a multigeneration JME family has been recently found in the ,1 -subunit of the GABAA receptor (GABRA1), predicting the single amino acid substitution A322D. We further characterized the functional consequences of this mutation by coexpressing ,1 -, ,2 - and ,2 -subunits in human embryonic kidney (HEK293) cells. By using an ultrafast application system, mutant receptors have shown reduced macroscopic current amplitudes at saturating GABA concentrations and a highly reduced affinity to GABA compared to the wild-type (WT). Dose,response curves for current amplitudes, activation kinetics, and GABA-dependent desensitization parameters showed a parallel shift towards 30- to 40-fold higher GABA concentrations. Both deactivation and resensitization kinetics were considerably accelerated in mutant channels. In addition, mutant receptors labelled with enhanced green fluorescent protein (EGFP) were not integrated in the cell membrane, in contrast to WT receptors. Therefore, the A322D mutation leads to a severe loss-of-function of the human GABAA receptor by several mechanisms, including reduced surface expression, reduced GABA-sensitivity, and accelerated deactivation. These molecular defects could decrease and shorten the resulting inhibitory postsynaptic currents (IPSCs) in vivo, which can induce a hyperexcitability of the postsynaptic membrane and explain the occurrence of epileptic seizures. [source] | ||||||||||||||||||||||||||||||||||||||||