Dissertations / Theses on the topic 'Ion action'
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1
Khan, Tanwir Rahman. "Action of philanthotoxin on ion channels of arthropod muscle." Thesis, University of Nottingham, 1994. http://eprints.nottingham.ac.uk/11229/.
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Calcium ions play an important role in many signalling pathways involved in normal cell metabolism. Pertrebations of normal Ca++ signalling may also play a pivotal role in the initiation of cell death. In these studies I have examined the influx of 45Ca++ into the extensor tibiae muscle of the locust (Schistocerca gregaria ). 45Ca++ entry could be stimulated by the addition of glutamate receptor-agonists or by activation of voltage activated calcium channels. L-glutamate, L-quisqualate and NMDA stimulated the influx of 45Ca++ while L-aspartate had only a small effect. DL-ibotenate, kainate, AMPA and glycine had no effect on 45Ca++ uptake (all agonists were tested at concentrations up to (100μM). Glycine (1μM) enhanced the 45Ca++ entry induced by NMDA and L-glutamate. Only the glycine potentiation of L-glu-stimulated responses was abolished in the presence of Mg++ (2mM) or AP5 (10μM) whereas the NMDA-stimulated response was completely abolished by these agents. These finding suggests that in the presence of glycine, L-glutamate may activate NMDA receptors and that in the absence of glycine L-glu-stimulated 45Ca++ entry occurs via activation of the qGluR. Depolarisation of the extensor tibiae muscles (50mM KCl) stimulated 45Ca++ influx by activation of voltage-sensitive calcium channels. Philanthotoxin-343 (0.1μM) had no effect on depolarisation activated calcium entry, however, nifedipine (1μM) an L-type calcium channel antagonist inhibited this Ca++ influx. Nifedipine did not inhibit L-glu-stimulated Ca++ entry suggesting that in these muscles L-type Ca++ channels are not involved in the Ca++ influx pathway following G1uR activation. Philanthotoxin-433 (PhTX-433) and many of its synthetic analogues are potent inhibitors of locust GluR. In the future these analogues may prove as useful potential neuroprotective agents or as novel pesticides. Over 100 analogues of PhTX-433 have been synthesized with changes made in the four regions of the structure, the thermospermine moiety, the tyrosyl moiety, the butyryl moiety and the terminal amino moiety. The effects of different concentrations (10-4M to 10-14M) of synthetic analogues of PhTX-433 (PhTX-343, PhTX-343-Arg, PhTX-4) were investigated in the 45Ca++ influx assay using locust extensor tibiae muscle. PhTX-343-Arg was more potent (IC50= - 7x10-9) than PhTX- 343 (IC50= - 10-8M) or PhTX-4 in blocking 45Ca H uptake. These findings were further supported by electrophysiological studies. The interaction of these synthetic analogues of philanthotoxin with GluR of locust muscle were further investigated by examining the effect of these compounds on evoked excitatory post synaptic potentials. In recent years control of ticks have been very important issue because of the social and economical damage they cause. Neuromuscular transmission is a main target site for the chemical control of many pests. Philanthotoxin and its analogues block the glutamate receptors which are involved in arthropod neuromuscular transmission and thus may prove useful as novel pesticides. The action of synthetic analogues of philanthotoxin (C7PhTX-343, DNP12-, PhTX-343 and PhTX-343) were examined on evoked excitatory postsynaptic potential in tick coxal muscle. These compounds all antagonized the evoked EPSP. C7PhTX-343 and DNP12-PhTX-343 exhibited same potency (IC50 = 10-8M) and both were more potent than PhTX-343 (IC50 ='2X10-5M). In recent years Xenopus oocyte has taken over a new role as a test tube for the study of the biogenesis, functional architecture and modulation of plasma membrane protein. Attempts were made to express mRNA from embryonic tissue of tick and locust leg muscle in to Xenopus oocyte for pharmacological studies. Xenopus oocytes failed to translate RNA faithfully and efficiently from these sources. Rat brain RNA injected oocytes used as control, expressed routinely.
2
Nilsson, Johanna. "Molecular mechanisms of local anaesthetic action on voltage-gated ion channels /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-748-7/.
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Zhang, Yanjun. "New insights of aldosterone action : a scanning ion conductance microscopy study." Thesis, Imperial College London, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.421900.
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Minard, Aisling M. "Understanding the mode of action of TRPC1/4/5 ion channel modulators." Thesis, University of Leeds, 2018. http://etheses.whiterose.ac.uk/22481/.
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Calcium ions are critical for cellular signalling and impact almost all aspects of cellular life. TRPC channels are non-selective cation channels permeable to both Na+ and Ca2+. TRPC channels are ubiquitously expressed in mammalian tissue and are linked to a wide range of pathological and physiological mechanisms. TRPC proteins can form both homo-and hetero-tetrameric channels. The natural composition and heteromerization of TRPC channels is poorly understood. However, they have been reported to be particularly promiscuous in the formation of heteromers. Over recent years numerous modulators of TRPC1/4/5 channels have been published; among them (-)-Engelrin A and Pico145 have emerged as particularly potent and specific activators and inhibitors of TRPC1/4/5 channels, respectively. However there still lacks evidence around the mode of action of these modulators and the ability to differentiate between TRPC1, TRPC4 and TRPC5 homomers and heteromers. This thesis explores approaches to unravel the mechanism of action of TRPC1/4/5 modulators. Firstly, recently published TRPC1/4/5 modulators, along with the pathology and advancements in structural information are reviewed in Chapter 1. Secondly, current approaches towards chemical labelling of target proteins is explored in Section 1.6 of Chapter 1. A range of cellular and biochemical techniques have been used in this thesis to unravel the mechanism of action of ion channel modulators and these have been briefly explained in Chapter 2. Chapter 3 details the development of novel TRPC5 modulators and investigation of the mechanism of action through calcium recording, electrophysiology and cyclic voltammetry experiments. Findings from these experiments suggest that the synthetic flavonol-based TRPC5 modulators act directly on the channel. The work in Chapter 4 details the use of photoaffinity probes based on the TRPC1/4/5 channel inhibitor, Pico145, to indicate a direct interaction with TRPC5. The work in this chapter identified that a known TRPC5 channel activator can distinguish between the closely related TRPC4 and TRPC5 proteins (~70% sequence identity). Structure activity relationships were explored on a series of TRPC5 inhibitors in Chapter 5. Overall this thesis demonstrates how multiple approaches can be used to unravel the mechanism of action of ion channel modulators in a synergistic manner.
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Muto, Yukiyo. "The synthesis and mode of action of NPPB and related compounds." Thesis, University of Canterbury. Biological Sciences, 2006. http://hdl.handle.net/10092/1522.
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5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) was normally recognised as a Cl- channel inhibitor, but its specificity is in question, since an inhibitory effect against K⁺ channels has been reported. To identify the significance of the molecules structural components, NPPB and related compounds, such as 2-(3-phenylpropylamino) benzoic acid (PPAB), 5- nitro-2-heptylamino benzoic acid (HANB) and 2-nitro-5-heptylamino benzoic acid (HANB-2) were synthesised by reductive amination using various aldehydes and amines. Using internodal cells of the giant green Characean algae, Nitella hookeri, the effects of NPPB and related compounds on cytoplasmic streaming and turgor regulation were determined. Previous experiments stated that cytoplasmic streaming was sensitive to NPPB, PPAB and HANB with IC₅₀ values of 24µmol/L, 455µmol/L, and 6.4mmol/L, respectively. In this report, the IC₅₀ values of purchased NPPB and niflumic acid were found to be 88.65µmol/L and 121.82µmol/L, respectively. Although the IC₅₀ value of purchased NPPB showed a slight difference from that of synthesised NPPB, the results of the cytoplasmic streaming experiment indicated the possibility of this analysis to be a simple assay system for analysing the effects of structural modification to ion channel inhibitors on their biological activity. Moreover, NPPB and PPAB seem to stimulate regulation of turgor pressure under hyperosmotic shock, which can be explained by a blockage of K⁺ efflux during osmotic stress leading to faster recovery of turgor regulation. Additionally, the results of cytosolic free Ca²⁺ analysis using aequorin technology also suggested that the possibility of this analysis to be used as a more direct measure of the inhibitory effect, while the cytoplasmic streaming analysis is a more indirect method. The preliminary results from this research suggest the significance of the simple assay systems for analysing the effects of structural modification ion channel inhibitors, which can be used for future study regarding ion channel structures.
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Alhewairini, Saleh Sulaiman. "Action and toxicity of pesticides on Caenorhabditis elegans and voltage-gated ion channels." Thesis, University of Nottingham, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.662202.
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The extensive applications of insecticides in agriculture and public health require appropriate methods to monitor their ecological and toxicological effects on target and non-target organisms. C.elegans was used as a model organism in this project as it has been successfully used to assess the toxicity of environmental pollutants including those in contaminated soil. C.elegans was used here to test various concentrations of insecticides/nematicides on wild-type and mutant worms. Direct observation and counting of pharyngeal muscle contraction was carried out and showed that incubation with anthelmintic or insecticide produced a concentration dependent inhibition of pharyngeal pumping in control animals. Results obtained showed that the CCA-l T-type calcium chatmelmay be such a target for pyrethroids and DDT. Worms lacking functional CCA-l (strain JD21) were less sensitive to both DDT and deltamethrin compared with wild-type N2 worms as pharyngeal pumping was reduced by DDT in N2 and JD21 st rains with ICso values of 909.2ppm and 9942ppm respectively and by deltamethrin with ICso values of 877.5ppm and 50527ppm respectively after a 1 h treatment. JD21 won11S were also more motile compared with N2 worms. EAT-2, an acetylcholine receptor subunit, may be affected by levamisole which is an acetylcholine receptor agonist, as DA465 worms lacking EAT -2 were less sensitive to levamiso le compared with N2 especially at lower concentrations.
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Campbell, G. "Is intravenous magnesium effective in cardiac arrhythmias?" Interim : Interdisciplinary Journal, Vol 7, Issue 2: Central University of Technology Free State Bloemfontein, 2008. http://hdl.handle.net/11462/385.
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Published ArticleMagnesium is the second most abundant intracellular cation with many control and regulatory functions. It regulates energy production and utilization and modulates activity of membrane ionic channels. Magnesium has direct control effects on cardiac myocyte ion channels making it useful in certain arrhythmias. Calcium is responsible for pacemaker excitation and for excitation-contraction coupling in myocytes but increased intracellular calcium produces early and late afterdepolarisations initiating arrhythmias. Magnesium regulates calcium channel activity preventing raised intracellular levels. Potassium channel activity is enhanced by magnesium hyperpolarizing the cell reducing arrhythmia generation. Magnesium is effective against long QT Torsade de Pointes. In rapid atrial fibrillation magnesium produces rate control slowing AV nodal conduction. Magnesium prevents digitalis toxicity due to associated hypomagnesemia.
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Mulaudzi, Takalani. "An investigation of the zinc binding characteristics of the RING finger domain from the human RBBP6 protein using heteronuclear NMR spectroscopy." Thesis, University of the Western Cape, 2007. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_9063_1260173635.
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Retinoblastoma binding protein 6 (RBBP6) is a 250 kDa human splicing-associated protein that is also known to interact with tumour suppressor proteins p53 and pRb and to mediate ubiquitination of p53 via its interaction with Hdm2. RBBP6 is highly up regulated in oesophageal cancer, and has been shown to be a promising target for immunotherapy against the disease. RBBP6 is also known to play a role in mRNA splicing, cell cycle control and apoptosis.
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Motloung, Setumo Victor. "Intense pulsed neutron generation based on the principle of Plasma Immersion Ion Implantation (PI3) technique." Thesis, University of the Western Cape, 2006. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_9599_1182748458.
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The development of a deuterium-deuterium/ tritium-deuterium (D-D/ D-T) pulsed neutron generator based on the principle of the Plasma Immersion Ion Implantation (PI3) technique is presented, in terms of investigating development of a compact system to generate an ultra short burst of mono-energetic neutrons (of order 1010 per second) during a short period of time (<
20&mu
s) at repetition rates up to 1 kHz. The system will facilitate neutron detection techniques, such as neutron back-scattering, neutron radiography and time-of-flight activation analysis.
Aspects addressed in developing the system includes (a) characterizing the neutron spectra generated as a function of the target configuration/ design to ensure a sustained intense neutron flux for long periods of time, (b) the system was also characterised as a function of power supply operating conditions such as voltage, current, gas pressure and plasma density.
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Nkosi, Mlungisi Moses. "Preparation and physico-chemical properties of nickel nanostructured materials deposited in etched ion-track membrane." Thesis, University of the Western Cape, 2005. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_6214_1182749152.
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The development of finely dispersed powders and superfine-grained materials intended for application in various areas of science and engineering is one of the challenges facing modern nanotechnology. Thus, specific fundamental and applied research was required in order to consolidate advancement made in preparing nano- and submicron crystalline composite materials.
Useful templates for electrochemical deposition of nanowires include porous alumina films formed by anodic oxidation of aluminium, nuclear track-etched porous membranes, nanochannel array-glass and mesoporous channel hosts. The properties of the nanowires are directly related to the properties of the nanoporous templates such as, the relative pore orientations in the assembly, the pore size distribution, and the surface roughness of the pores. The template synthesis method, based on the use of porous polymeric and inorganic matrixes, is now actively used for synthesis of such composite materials. The method allows the chemical and/or electrochemical synthesis of nano- and microstructured tubes and wires consisting of conducting polymers, metals and semiconductors.
In this study various technological challenges relating to template synthesis and development of nickel nano- and microstructures on adequately strong and durable substrates were investigated. The two methods used were the electrochemical and chemical deposition. &ldquo
Hard nickel&rdquo
bath solution was used for optimal nickel deposition. This optimization included investigating variables such as the template structure, type of electrolyte and form of electrolytic deposition. Scanning Electron Microscopy was used to investigate the structures of template matrixes and the resultant materials. The cyclic voltammetry method was applied for the analysis of electrochemical properties and hydrogen evaluation reaction of nano- and microstructured nickel based electrodes. The activity of composite nano- and microstructured materials in various configurations resulting from pore filling of template matrices by nickel was explored. Studies of the physical structure and chemical properties of the nanostructured materials included investigating the necessary parameters of template matrices. The optimum conditions of synthesis, which allowed development of materials with the highest catalytic activity, were determined.
The effect of the template structure on microcrystallinity of the catalyst particles was established using the XRD method. Different new types of non-commercial asymmetric ion track membranes has been tested for nanostructure preparation. The catalytic activity of the new developed nanomaterials is higher as compared to materials using commercial templates. The procedures to modify the newly developed nickel catalyst with Pt, Pd and Pt-Pd alloy have been developed. The Pt and Pt-Pd alloy containing catalyst showed the best performance in water electrolysis. In this work, the promising role for specific application of the new materials in hydrogen economy has been demonstrated.
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Adeniyi, Olushola Rotimi. "Ion track modification of polyimide film for development of palladium composite membrane for hydrogen separation and purification." Thesis, University of the Western Cape, 2011. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_8563_1330330939.
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South Africa s coal and platinum mineral resources are crucial resources towards creating an alternative and environmentally sustainable energy system. The beneficiation of these natural resources can help to enhance a sustainable and effective clean energy base infrastructure and further promote their exploration and exportation for economics gains. By diversification of these resources, coal and the platinum group metals (PGMs) especially palladium market can be further harnessed in the foreseeable future hence SA energy security can be guaranteed from the technological point of view. The South Africa power industry is a critical sector, and has served as a major platform in the South African socio-economic development. This sector has also been identified as a route towards an independent energy base, with global relevance through the development of membrane technologies to effectively and economically separate and purify hydrogen from the gas mixtures released during coal gasification. The South Africa power industry is a critical sector, and has served as a major platform in the SA&rsquo
s socio-economic development. This sector has also been identified as a route towards an independent energy base, with global relevance through the development of membrane technologies to effectively and economically separate and purify hydrogen from the gas mixtures released during coal gasification. Coal gasification is considered as a source of hydrogen gas and the effluent gases released during this process include hydrogen sulphide, oxides of carbon and nitrogen, hydrogen and other particulates. In developing an alternative hydrogen gas separating method, composite membrane based on organic-inorganic system is being considered since the other available methods of hydrogen separation are relatively expensive.
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Yalala, Bongani Ndhlovu. "Ion exchange resins an functional fibres :a comparative study for the treatment of brine waste water." Thesis, University of the Western Cape, 2009. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_8342_1298358875.
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To improve the adsorption capacity of polyacrylonitrile (PAN) fibres, hydrophilic amidoxime fibres were prepared by subsequent conversion of the cyano groups to an amidoxime group by reacting with hydroxylamine at 80°
C at an optimum amidoximation time of 2 hrs. The amidoxime fibre was hydrolyzed/alkali treated in a solution of sodium hydroxide to enhance or improve the adsorption properties. This was followed by characterization of the amidoxime and hydrolyzed fibres using Scanning electron microscopy (SEM)
Fourier transform Infrared Spectroscopy (FTIR) and exchange capacity (cationic and anionic). SEM showed that the hydrolysis process made the surface of Amidoxime fibre rougher than that of Polyacrylonitrile fibre. FTIR revealed that the hydrolyzed Amidoxime fibres contained conjugated imine (-C=N-) sequences. Functionalization enhanced the sorption of amidoxime fibres by an increase of 20 % in the cationic exchange capacity. This was achieved by the part conversion of the cyano groups into the carboxylic acid groups. The fibres showed faster kinetics largely due the available exchange sites on the surface of the fibres hence the equilibration was achieved much quicker.
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Tempesta, Zechari Ryan. "Action Potential Simulation of the Hirudo Medicinalis's Retzius Cell in MATLAB." DigitalCommons@CalPoly, 2013. https://digitalcommons.calpoly.edu/theses/1127.
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Modification of Hodgkin and Huxley’s experimentally derived set of nonlinear differential equations was implemented to accurately simulate the action potential of the Hirudo Medicinalis’s Retzius cell in MATLAB under analogous conditions to those found in the Retzius cell environment. The voltage-gated sodium and potassium channel responses to changes in membrane potential, as experimentally determined by Hodgkin and Huxley, were manipulated to suit simulation parameters established by electrophysiological Retzius cell recordings. Application of this methodology permitted additional accurate simulation of the Hirudo Medicinalis’s P cell under analogous conditions to those found in the P cell environment. Further refinement of this technique should allow for the voltage-gated behavioral based simulation of action potential waveforms found in variety of neurons under simulation conditions analogous to the nerve cell environment.
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Weidenbach, Stevi. "INVESTIGATION OF THE MECHANISM OF ACTION FOR MITHRAMYCIN AND THE BIOSYNTHESIS OF L-REDNOSE IN SAQUAYAMYCINS." UKnowledge, 2017. http://uknowledge.uky.edu/pharmacy_etds/77.
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Natural products continue to be a major chemical lead matter for drug discovery due to their diverse chemical structures and bioactivities. Clinically significant natural products include anti-cancer and anti-infective compounds and while many more of these compounds show promising bioactivity, their clinical relevance is often limited by toxicity or poor solubility. Combinatorial biosynthesis can be employed to modify existing chemical scaffolds towards reducing these limitations. To fully take advantage of these biochemical tools, it is important to understand the biosynthesis and mechanism of action of the molecules.
Saccharides in glycosylated natural products provide specific interactions with cellular targets and are often crucial for a compound’s bioactivity. Genetic engineering of sugar pathways can modify glycosylation patterns leading to the diversification of natural products. Saquayamycins (SQN) H and I are cytotoxic angucycline antibiotics containing five deoxyhexoses including the rare amino sugar rednose. Elucidating the biosynthetic pathway of rednose could add to the arsenal of combinatorial biosynthesis tools for drug development. Our research goal of investigating the rednose biosynthetic pathway was pursued through two specific aims: the identification of the Streptomyces sp. KY 40-1 gene cluster involved in the biosynthesis of SQN H and I (sqn) (specific aim 1), and the validation of the proposed L-rednose biosynthetic pathway up to the glycosyl transfer through enzymatic synthesis of NDP-3,6-dideoxy-L-idosamine (specific aim 2). The sqn gene cluster revealed deoxysugar biosynthetic genes that could be used to alter glycosylation patterns to generate novel compounds while the enzymatic synthesis afforded novel genetic engineering tools to generate novel TDP-deoxysugars that could be used to diversify compounds such as aminoglycosides to circumvent resistance mechanisms. The first step to generate TDP-glucosamine enzymatically was accomplished, however later steps were unsuccessful.
The aureolic acid mithramycin (MTM) was recently tested in clinical trials for Ewing sarcoma following the discovery of MTM as a potent inhibitor of the oncogenic transcription factor EWS-FLI1 present only in Ewing sarcoma cells It is understood that MTM binds the minor groove of G/C rich DNA as an Mg2+-coordinated dimer disrupting transcription of proto-oncogenes; however, the DNA recognition rules were not completely understood, making further interrogation of MTM’s DNA binding preferences necessary. This research goal of further understanding the mechanism of action for MTM was approached through two specific aims: the investigation of the dimerization of MTM (specific aim 3), and the investigation of MTM’s DNA binding preferences (specific aim 4). This work established that MTM and its biosynthetic precursor premithramycin B (PreMTM B), and several MTM analogues with modified 3-side chains: mithramycin SDK (MTM SDK), mithramycin SA tryptophan (MTM SA-Trp), and mithramycin SA alanine (MTM SA-Ala) dimerize even in the absence of DNA under physiologically relevant conditions. The study also demonstrated that modification of the 3-side chain modulates DNA binding affinity of MTM analogues, established a minimum MTM binding site on DNA, and revealed MTM DNA recognition is driven by direct (sequence) and not indirect (conformation) readout laying the foundation for subsequent research based on the interaction between MTM, DNA, and the oncogenic transcription factor EWS-FLI1 in the rational design of new MTM analogues for the treatment of Ewing sarcoma.
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Pahlavan, Sara [Verfasser], and Peter [Akademischer Betreuer] Lipp. "Ion Currents, Action Potentials and Their Modulation by Gαq/11 Signaling Pathways in The Mouse Heart / Sara Pahlavan. Betreuer: Peter Lipp." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2013. http://d-nb.info/1052908861/34.
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Якім'юк, Анна Дмитрівна, Мар'яна Іванівна Кривчанська, and Мар'яна Іванівна Грицюк. "The indices of ion-regulating renal function at melatonin administration on the bankground of anaprilinum action under condition of standard lighting." Thesis, Abstracts journal: 13-th Edition of Craiova International Medical Students Conference. - 10-th-13-th November 2011. - Craiova, Romania/, 2011. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/2181.
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Davids, Wafeeq. "Consolidated Nanomaterials Synthesized using Nickel micro-wires and Carbon Nanotubes." Thesis, University of the Western Cape, 2007. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_9685_1264387931.
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Mabovu, Bonelwa. "Brine treatment using natural adsorbents." Thesis, University of the Western Cape, 2011. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_3665_1319180742.
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The current study investigated application of natural adsorbents in brine treatment. Brines are hypersaline waters generated in power stations and mining industries rich in Mg2+, K+, Ca2+, Na+, SO4 2- , Cl- and traces of heavy metals, thus there is a need for these brines to be treated to recover potable water and remove problematic elements. Natural adsorbents have been successfully used in waste water treatment because of their high surface area and high adsorptive properties when they are conditioned with acid or base. The investigation of pH showed that natural adsorbents did not perform well at low pH of 4 and 6. The adsorbents were able to work efficiently at the natural pH of 8.52 of the brine solution. These results show that natural adsorbents hold great potential to remove cationic major components and selected heavy metal species from industrial brine wastewater. Heterogeneity of natural adsorbents samples, even when they have the same origin, could be a problem when wastewater treatment systems utilizing natural clinoptilolite and bentonite are planned to be developed. Therefore, it is very important to characterize the reserves fully in order to make them attractive in developing treatment technologies.
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Garnica, Rodríguez Jairo Ivan. "Polyaniline-silica-nafion composite membranes for direct methanol fuel cells /." [St. Lucia, Qld.], 2005. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe18986.pdf.
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Ujma, Jakub. "Development and use of novel instrumentation for structural analysis of gaseous ions." Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/development-and-use-of-novel-instrumentation-for-structural-analysis-of-gaseous-ions(7c299a20-a306-4851-85de-5d2827bc549e).html.
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Traditional solution and solid state approaches (Nuclear Magnetic Resonance, X-Ray Crystallography) are methods of choice when analysing both biological and inorganic analytes. However, the characterisation of transient species, often encountered in self-assembling systems, is difficult. Such systems rarely produce crystals of high quality and due to their dynamic nature; their structures are difficult to study with NMR. Hyphenated gas phase methods which rely on mass spectrometry detection offer simultaneous structural analysis and direct stoichiometry measurement. As a consequence, it is possible to investigate specific, non-interacting molecules and molecular complexes in an isolated environment. This thesis focuses on the development and applications of two such methods - ion mobility mass spectrometry (IM-MS) and cold ion spectroscopy. IM-MS measurements yield a so called collisional cross sectional area (CCS). This parameter can be pictured as a rotationally averaged, shadow projection of a molecule structure. When correlated with the ion abundance, a CCS distribution yields intuitively interpretable information about the conformational preferences of an isolated molecule. Although indispensable in describing a "global" geometrical structure, the CCS parameter itself provides a limited insight into the local structural features of the assembly. Ion spectroscopy, both in the UV and IR regions, can provide an extra layer of highly descriptive information. Here, we present several cases where the above techniques have been applied. With the aid of IM-MS, we have analysed the geometry of inorganic supramolecular assemblies, highlighting the stability of particular metal-ligand interactions. Using cold ion spectroscopy, we have assessed the fine structural information of self-assembled oligomers of an amyloidogenic peptide. We correlated spectral features of isolated oligomers to features observed in the mature fibrils; therefore attempting to delineate the events in early stages of amyloidogenic aggregation. A major part of this report focusses on technological aspects of the design and development of a high resolution, variable temperature ion mobility mass spectrometer (VT-IM-MS). The thermal stability of molecules is a vital aspect in industrial process development and formulation science. Solution phase Differential Scanning Calorimetry (DSC) is a widely applied technique, allowing to monitor reversibility of thermally induced conformational transitions, a key aspect in protein folding analysis. The instrument reported here aims to provide parallel information about gaseous ions, with a particular focus on protein ions. Capabilities of the newly built instrument have been tested using small, rigid molecules, a small protein and a large multiprotein complex.
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Ednie, Andrew. "Aberrant Sialylation Alters Cardiac Electrical Signaling." Scholar Commons, 2012. http://scholarcommons.usf.edu/etd/4312.
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In the heart, electrical signaling is responsible for its rhythmicity and is necessary to initiate muscle contraction. The net electrical activity in a cardiac myocyte during a contraction cycle is observed as the action potential (AP), which describes a change in membrane potential as a function of time. In ventricular cardiac myocytes, voltage-gated sodium channels (Nav) and voltage-gated potassium channels (Kv) play antagonistic roles in shaping the AP with the former initiating membrane depolarization and the latter repolarizing it. Functional changes in the primary cardiac Nav isoform, Nav 1.5, or any one of the many Kv isoforms expressed in the ventricle, as evidenced by those characterized in various congenital and/or acquired etiologies, can lead to severe cardiac pathologies. Nav and Kv are large transmembrane proteins that can be extensively post-translationally modified through processes that include glycosylation. The sequential glycosylation process typically ends with negatively charged sialic acid residues added through trans-Golgi sialyltransferase activity. Sialyltransferases belong to a much larger group of glycogene products that number in the hundreds and are responsible for creating a complex and variable glycan profile (glycome) unique to different cell types and tissues. Sialic acids impact Nav and Kv function likely by contributing to the extracellular surface potential and thereby causing channels to gate following smaller depolarizations. Additionally, developmentally regulated sialylation contributes to cardiac myocyte excitability in the neonatal mouse atria. However, little is understood concerning how the glycosylation machinery (glycogene products) influences cell and tissue electrical signaling. The sialytransferase Β-galactoside α-2,3-sialyltransferase 4 (ST3Gal4) adds sialic acids to galactose residues of N- and O-linked glycans through α-2,3-linkgages. ST3Gal4 is uniformly expressed throughout the chambers and developmental stages of the heart and therefore is likely a useful target to question whether and how glycosylation impacts these events. Additionally, diseases of glycosylation often cause symptoms that are consistent with changes in excitability that include arrhythmias and seizures. Congenital disorders of glycosylation lead to variably reduced glycoprotein and glycolipid glycosylation. However, because sialic acids are typically the terminal residues added to glycan structures, disease-related reduced glycosylation often leads to fewer sialic acids being attached. In addition, Chagas disease, which results in pathological changes in cardiac electrical function, may reduce sialic acids directly. Because of this, the ST3Gal4-/- strain was also used to investigate the role of glycosylation in the pathological cardiac electrical remodeling often associated with these diseases. The methodologies included cellular, tissue and whole-animal electrophysiology as well as biochemical assays. The data indicate that deletion of ST3Gal4 significantly affects Nav sialylation and gating with no change in maximum current density or protein expression. ST3Gal4 deletion also depolarizes the activation gating of both voltage-dependent kinetic components of repolarization found in the mouse ventricle: Ito and IKslow; however unlike the effect on INa, ST3Gal4 gene deletion causes a reduction in the peak IK density. Protein expression of the putative Kv isoforms responsible for Ito and IKslow was variably affected by ST3Gal4 gene deletion with Kv1.5 and Kv4.2 demonstrating no differences in protein densities. Contrastingly, a small but significant reduction in Kv2.1 protein from ST3Gal4-/- ventricular tissue was observed. In addition to effects on Nav and Kv activity, ST3Gal4 expression is necessary for normal cellular electrical signaling as demonstrated by a reduction in cellular refractory period and alterations in AP waveforms that include a slowing of cellular conduction and an extension of AP duration in ventricular myocytes from ST3Gal4-/- mice. Concurrent with aberrant excitability at the cellular level, the ST3Gal4-/- left ventricular epicardium demonstrated a reduced refractory period and was more susceptible to arrhythmias as observed through optical mapping studies. Additionally, ECGs of ambulatory ST3Gal4-/- mice demonstrated that deletion of the gene causes modest aberrant conduction under basal conditions and, in preliminary studies, appears to increase susceptibility to arrhythmias following a cardiac challenge, in the form of a low dosage of the Β-adrenergic agonist isoproterenol, suggesting a reduction in repolarization reserve in ST3Gal4 hearts. Based on the data reported here, it is apparent that relatively minor perturbations in the cardiac glycome cause significant changes in cardiac electrical signaling. These data highlight the role of glycosylation in normal physiology and underscore it as an important mediator in diseases where it may be altered.
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Cauquil-Caubère, Isoline. "Protection des transporteurs de glutamate astrocytaires contre la toxicité des radicaux hydroxyles. Modélisation et synthèse de nouveaux capteurs de radicaux, protection de la capture de glutamate sur cultures primaires d'astrocytes et action antiradicalaire chez le rat vigile." Montpellier 1, 1998. http://www.theses.fr/1998MON13514.
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Kasongo, Wa Kasongo Jean B. "Synthesis and characterization of micro- and mesoporous materials for low temperature selective catalytic reduction of nitrogen oxides." Thesis, University of the Western Cape, 2011. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_2469_1320325768.
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In summary, it has been shown during this study that bimetallic Fe and Mn containing catalysts can be prepared by wet impregnation and not by ion exchange because of the competition between two different metals at different oxidation number. Only a single metallic phase catalyst could be prepared successfully by using ion exchange.
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Armstrong, Scott. "Electrophysiological investigation of the mechanism of action of xenon on ion-channels and determination of the neuroprotective potential of xenon in an in vivo model of traumatic brain injury." Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/24766.
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Xenon is a general anaesthetic gas with neuroprotective properties. Inhibition of the N-methyl-D-aspartate (NMDA) receptor glycine co-agonist site has been shown to mediate xenon neuroprotection against ischemic injury in vitro. Site-directed mutagenesis was used to produce point mutations in the GluN1 subunit of rat NMDA receptors. These were then expressed in HEK293 cells and the responses of mutant GluN1/GluN2A receptors to glycine and anaesthetics assessed using patch-clamp electrophysiology. Two mutations of the phenylalanine 758 site were found to eliminate xenon binding to the receptor without altering glycine affinity or the binding of sevoflurane and isoflurane. These selective mutations will allow for knock-in animals to be used to dissect the mechanism(s) underlying xenon neuroprotection and anaesthesia in vivo. The ability of the other noble gases (helium, neon, argon, and krypton) to influence two known molecular targets of xenon - the NMDA receptor and the TREK-1 channel - was also assessed using patch-clamp electrophysiology. These were found to have no influence on either NMDA receptors or TREK-1 channels. Finally, xenon's neuroprotective efficacy against traumatic brain injury (TBI) in vivo was assessed using the rodent controlled cortical impact model of TBI. Focal contusion injury was administered to male C57 mice and animals administered either 75% xenon or control treatment for three hours. Xenon-treated animals performed better in functional tests and displayed favourable outcomes in brain histology, as compared to control animals. This data provides the first evidence of a neuroprotective effect for xenon against TBI in vivo.
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Agi, Egemen. "Mathematical Modeling Of Gate Control Theory." Master's thesis, METU, 2009. http://etd.lib.metu.edu.tr/upload/3/12611468/index.pdf.
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The purpose of this thesis work is to model the gate control theory, which explains the modulation of pain signals, with a motivation of finding new possible targets for pain treatment and to find novel control algorithms that can be used in engineering practice. The difference of the current study from the previous modeling trials is that morphologies of neurons that constitute gate control system are also included in the model by which structure-function relationship can be observed. Model of an excitable neuron is constructed and the response of the model for different perturbations are investigated. The simulation results of the excitable cell model is obtained and when compared with the experimental findings obtained by using crayfish, it is found that they are in good agreement. Model encodes stimulation intensity information as firing frequency and also it can add sub-threshold inputs and fire action potentials as real neurons. Moreover, model is able to predict depolarization block. Absolute refractory period of the single cell model is found as 3.7 ms. The developed model, produces no action potentials when the sodium channels are blocked by tetrodotoxin. Also, frequency and amplitudes of generated action potentials increase when the reversal potential of Na is increased. In addition, propagation of signals along myelinated and unmyelinated fibers is simulated and input current intensity-frequency relationships for both type of fibers are constructed. Myelinated fiber starts to conduct when current input is about 400 pA whereas this minimum threshold value for unmyelinated fiber is around 1100 pA. Propagation velocity in the 1 cm long unmyelinated fiber is found as 0.43 m/s whereas velocity along myelinated fiber with the same length is found to be 64.35 m/s. Developed synapse model exhibits the summation and tetanization properties of real synapses while simulating the time dependency of neurotransmitter concentration in the synaptic cleft. Morphometric analysis of neurons that constitute gate control system are done in order to find electrophysiological properties according to dimensions of the neurons. All of the individual parts of the gate control system are connected and the whole system is simulated. For different connection configurations, results of the simulations predict the observed phenomena for the suppression of pain. If the myelinated fiber is dissected, the projection neuron generates action potentials that would convey to brain and elicit pain. However, if the unmyelinated fiber is dissected, projection neuron remains silent. In this study all of the simulations are preformed using Simulink.
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Diserbo, Michel. "Action du Platelet-Activating Factor (PAF) sur les cellules de la lignée N1E-115 : effets sur la concentration du calcium libre cytosolique et sur les flux ioniques transmembranaires." Université Joseph Fourier (Grenoble), 1995. http://www.theses.fr/1995GRE10073.
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Le paf (1-o-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) est aujourd'hui reconnu comme un des plus importants neuromediateurs lipidiques. Dans ce travail, nous montrons une action du paf sur les cellules de la lignee de neuroblastome n1e-115. Par les techniques de liaison, nous avons mis en evidence sur ces cellules la presence de deux types de recepteurs du paf. L'activation de ces recepteurs par des concentrations physiologiques de paf produit une accumulation d'inositol triphosphate, et une augmentation rapide et transitoire du calcium libre cytosolique. Cette augmentation du calcium libre cytosolique fait intervenir a la fois une redistribution du calcium intracellulaire et des influx de calcium externe. Ces influx de calcium passent essentiellement via des canaux permeables aux ions ca#2#+ de type receptor-operated channel. Nous montrons la presence, sur ces cellules, de canaux permeables au ca#2#+ et activables par la thapsigargine correspondant tres probablement a des canaux calciques activables via la depletion des reserves intracellulaires. Ces canaux interviennent dans la reponse induite par le paf. A l'aide de la technique de voltage impose sur cellule entiere, nous avons mis en evidence une activation possible par le paf des canaux calciques sensibles au voltage de type l. Cependant, cette derniere action du paf ne participe que, de facon minime, aux entrees de ca#2#+. L'activation de ces canaux est, en effet, bloquee par une hyperpolarisation transitoire en reponse a l'activation par le paf de canaux potassiques du type bk(ca). Cette derniere action du paf est la consequence de la seule augmentation du calcium libre cytosolique, et ne resulte pas d'une action directe du paf sur ces bk(ca). Enfin, a l'aide de la technique du patch-clamp, nous n'avons pas mis en evidence l'effet du paf sur les autres permeabilites ioniques membranaires de ces cellules (courants na#+ et k#+ sensibles au potentiel)
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Pardo, Pastor Carlos 1989. "Piezo ion channels in cancer cell mechanotransduction." Doctoral thesis, Universitat Pompeu Fabra, 2018. http://hdl.handle.net/10803/664209.
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The mechanical dependence of transformation and metastasis is an emerging field, but the role of mechanosensitive channels has been largely omitted. This thesis focuses on the roles played by the mechanosensitive ion channels Piezo1 and Piezo2 in the transduction of mechanical stimuli (confinement, adhesion, substrate rigidity, adhesive ligand concentration) by cancer cells.
In a first chapter, we show that confinement triggers Piezo1-mediated calcium entry. This activates phosphodiesterase 1, reducing cAMP levels and, consequently, PKARac1 activity, relieving Myosin II from its inhibition. We also find a parallel, direct activation of Myosin II by confinement. As a combined result, cells stiffen and optimize their adhesion-free migration mode, usually responsible for in vivo migration during metastatic invasion. Piezo1 knockdown supresses confinement-induced calcium entry and impairs the underlying circuitry in ovarian epithelial (CHO) or melanoma (A375) cells. As a result, siPiezo1 cells show reduced migratory capacity under confinement.
In the second chapter, we discover an essential role for Piezo2 as a transducer of environmental mechanical cues into RhoA activation to modulate the mechanobiological responses of MDA-MB-231-BrM2 brain metastatic breast cancer cells. Piezo2 knockdown disturbs stress fibre formation, adhesion orientation, force transmission and nuclear accumulation of the malignant co-transcriptional activator YAP, and this is phenocopied by extracellular calcium suppression. Promoting Actin polymerization with jasplakinolide or by over-expressing constitutively active forms of Rho or mDia1 restores stress fibres and nuclear YAP accumulation. In addition, Piezo2 knockdown disrupts several pro-metastatic functions: cell proliferation, migration, invadopodia formation, extracellular matrix degradation, and secretion of SERPINB2, a protein needed for protecting invasive cells from brain parenchymal defence mechanisms.
The works presented in this thesis unveil important roles for Piezo channels as a first line of mechanical input detectors in distinct cells. These discoveries are relevant for several fields, e.g. cancer research, and highlight the importance of ion channels as transducers of environmental stimuli.La dependència mecànica de la transformació i la metàstasi és un camp d’estudi / de recerca emergent, però el paper que hi juguen els canals iònics mecanosensibles s’ha omès fins ara. Aquesta tesi se centra en els rols dels canals Piezo1 i Piezo2 en la transducció d’estímuls mecànics per cèl·lules canceroses, com ara confinament, adhesió, rigidesa del substrat, concentració de lligands adhesius. En un primer capítol, mostrem que el confinament dispara l’entrada de calci per mitjà de Piezo1. Això activa la fosfodiesterasa 1, que redueix els nivells d’AMPc i, en conseqüència, l’activitat PKARac1, que deixen d’inhibir Miosina II. També trobem una activació paral·lela de Miosina II directament per confinament. Com a resultat final, les cèl·lules guanyen rigidesa i optimitzen el seu mode migratori independent d’adhesions, que és el preponderant in vivo durant la invasió metastàtica. Reduir els nivells de Piezo1 suprimeix l’entrada de calci induïda per confinament i desactiva el circuit subjacent en cèl·lules ovàriques epitelials (CHO) i de melanoma (A375). Això minva la capacitat migratòria de les cèl·lules siPiezo1. En un segon capítol, descobrim un rol essencial per a Piezo2 com a activador de RhoA en resposta a estímuls mecànics. Això modula les respostes mecanobiològiques de les cèl·lules MDA-MB-231-BrM2, de càncer de mama metastàtic a cervell. La reducció dels nivells de Piezo2 destorba la formació de fibres d’estrès, l’orientació de les adhesions, la transmissió de forces i l’acumulació nuclear del regulador transcripcional prometastàtic YAP. Suprimir el calci extracel·lular fenocòpia aquests resultats. Promoure la polimerització d’Actina amb jasplaquinolida o mer mitjà de la sobreexpressió de formes constitutivament actives de RhoA o mDia1 restableix les fibres d’estrès i l’acumulació nuclear de YAP. A més, la reducció de Piezo2 suspèn diverses funcions prometastàtiques: proliferació cel·lular, migració, formació d’invadopodis, degradació de la matriu extracel·lular i secreció de SERPINB2, una proteïna necessària per protegir les cèl·lules invasores dels mecanismes de defensa del parènquima cerebral. Els treballs presentats en aquesta tesi desvelen rols importants pels canals Piezo com a una primera línia de detectors d’estímuls mecànics en diferents tipus cel·lulars. Aquests descobriments són rellevants per a diversos àmbits, com ara la recerca en càncer, i remarquen la importància dels canals iònics com a transductors d’estímuls ambientals.
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Caulfield, Jason Patrick. "Preparation for nerve membrane potential readings of a leech, laboratory setup and dissection process." DigitalCommons@CalPoly, 2009. https://digitalcommons.calpoly.edu/theses/130.
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A well documented laboratory setup, leech preparation process, and bio-potential data recording process are needed. Repeatability and quality data recordings are essential and thus dictate the requirements of the laboratory setup and processes listed above. Advances in technology have both helped and hindered this development. While very precise equipment is required to record the low voltage bio-potentials, noisy electronic equipment and wires surrounding the work area provide high levels of interference. Proper laboratory setup and data recording processes, however, limit the unwanted interference. Quality data can only be recorded from a properly handled and prepared leech subject. Proper setup and procedures result in quality recordings which lend a clean signal for furthering the understanding of nerve functionality. The electrophysiology lab at California Polytechnic State University in San Luis Obispo is an example of a proven lab setup for high quality signal capture.
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Korhonen, T. (Topi). "Mathematical modeling of the regulation, development and genetically engineered experimental models of cardiac excitation-contraction coupling." Doctoral thesis, University of Oulu, 2009. http://urn.fi/urn:isbn:9789514290756.
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Abstract
Excitation-contraction coupling (ECC) is a process linking the electrical excitation of the muscle cell (myocyte) membrane to the contraction of the cell. In this study the possibilities of mathematical modeling were studied in current ECC research. Mathematical modeling was employed in two distinct ECC research areas, the enzymatic regulation of ECC and ECC during cardiac myocyte development. Despite the distinction, both of these are extremely complex biological systems characterized by diverse and partly contradictory reported experimental results, with a large part based on genetically engineered animal models.
Novel mathematical models were developed for both of these research areas. The model of ventricular myocyte ECC with calmodulin-dependent protein kinase II (CaMKII)-mediated regulation faithfully reproduced the heart-rate dependent regulation of ECC. This regulation is thought to be the major effect of CaMKII-mediated regulation. The model of the embryonic ventricular myocyte provided the first comprehensive system analysis of how the embryonic heartbeat is generated at the cellular level. A similar type of model was also developed to show the notable differences between neonatal and adult ventricular myocyte ECC.
The mathematical models of ECC presented in this study were further used to simulate ECC in genetically engineered myocytes. The cellular mechanisms of genetically engineered animal models could be better understood by employing mathematical modeling in parallel to experimental characterization of the animal model. It was found in simulations that the indirect consequences and the compensatory mechanisms induced by genetic modification may have a more significant effect on ECC than the direct consequences of the modification.
To understand the overwhelming complexity of biological systems including ECC, competent system analysis tools, such as mathematical modeling, are required. The purpose of mathematical modeling is not to replace the experimental studies, but to provide a more comprehensive system analysis based on the experimental data. This system analysis will help in planning subsequent experiments needed to gain the most relevant information about the studied biological system.
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Грищенко, Вікторія Андріївна. "Вплив йонного опромінення на структурно-фазові перетворення в тонких плівках Cu/Cr, Ni/Cr, Ni/Cu/Cr при термічному відпалі." Master's thesis, КПІ ім. Ігоря Сікорського, 2020. https://ela.kpi.ua/handle/123456789/34696.
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Магістерська дисертація: 81 сторінка, 41 рисунків, 12 таблиць, 38 літературних джерел.
Об’єкт досліджень:структурно-фазові перетворення в наношарових композиціях Cu/Cr, Ni/Cr, Ni/Cu/Cr за умов вакуумного термічного відпалу та з додатковою йонно-плазмовою обробкою.
Мета роботи: дослідження особливостей впливу попередньої йонно-плазмової обробки на структурно-фазові перетворення у тонких плівках Cu/Cr, Ni/Cr, Ni/Cu/Crза умов термічного відпалу.
Методи дослідження: мас-спектрометрія вторинних йонів, трансмісійна електронна мікроскопія, in-situ високоенергетична електронна дифракція.
Досліджено особливості формування структури та фазового складу систем Cu/Cr, Ni/Cr та Ni/Cu/Cr при відпалі у вакуумі у широкому температурному інтервалі.
Тонкоплівкові композиції були одержані шляхом термічного випаровування у вакуумі і, в подальшому, піддавалися йонно-плазмовій та термічній обробці до температур 690 °C. Після обробки плівки досліджено методами мас-спектрометрії вторинних йонів, трансмісійною електронною мікроскопією, in-situ високоенергетичною електронною дифракцією.
Зафіксовано розвиток окисно-відновних процесів, які ефективно контролюються шляхом використання додаткового плазмового оброблення плівок. Йонний низькоенергетичний вплив стабілізує структуру досліджуваних систем шляхом гальмування процесів рекристалізації.Master thesis: 81 pages, 41 figure, 12 tables, 38 references. The object of research is structural-phase transformations in nanolayer compositions Cu/Cr, Ni/Cr, Ni/Cu/Cr under conditions of vacuum thermal annealing and with additional ion-plasma action. The purpose is to study the peculiarities of the influence of preliminary ion plasma action on structural-phase transformations in thin films Cu/Cr, Ni/Cr, Ni/Cu/Cr under conditions of thermal annealing. Research methods: secondary-ion mass spectrometry, transmission electron microscopy, in-situ high-energy electron diffraction. The peculiarities of the formation of the structure and phase composition of the Cu/Cr, Ni/Cr and Ni/Cu/Cr systems during annealing in vacuum in a wide temperature range have been studied. The thin film compositions were obtained by thermal evaporation in vacuum and subsequently subjected to ion-plasma and heat treatment to temperatures of 690 °C. After processing the film, it was investigated by secondary-ion mass spectrometry, transmission electron microscopy, in-situ high-energy electron diffraction. The development of redox processes, which are effectively controlled by the use of additional plasma treatment of films, has been recorded. Ionic low-energy effect stabilizes the structure of the studied systems by inhibiting recrystallization processes.
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Bartos, Daniel C. "Mechanistic Basis for Atrial and Ventricular Arrhythmias Caused by KCNQ1 Mutations." UKnowledge, 2013. http://uknowledge.uky.edu/physiology_etds/8.
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Cardiac arrhythmias are caused by a disruption of the normal initiation or propagation of electrical impulses in the heart. Hundreds of mutations in genes encoding ion channels or ion channel regulatory proteins are linked to congenital arrhythmia syndromes that increase the risk for sudden cardiac death. This dissertation focuses on how mutations in a gene (KCNQ1) that encodes a voltage-gated K+ ion channel (Kv7.1) can disrupt proper channel function and lead to abnormal repolarization of atrial and ventricular cardiomyocytes.
In the heart, Kv7.1 coassembles with a regulatory protein to conduct the slowly activating delayed rectifier K+ current (IKs). Loss-of-function KCNQ1 mutations are linked to type 1 long QT syndrome (LQT1), and typically decrease IKs, which can lead to ventricular action potential (AP) prolongation. In patients, LQT1 is often characterized by an abnormally long corrected QT (QTc) interval on an electrocardiogram (ECG), and increases the risk for polymorphic ventricular tachycardias.
KCNQ1 mutations are also linked to atrial fibrillation (AF), but cause a gain-of-function phenotype that increases IKs. Surprisingly, patients diagnosed with both LQT1 and AF are increasingly identified as genotype positive for a KCNQ1 mutation. The first aim of this dissertation was to determine a unique functional phenotype of KCNQ1 mutations linked to both arrhythmia syndromes by functional analyses via the whole-cell patch clamp technique in HEK293 cells.
A proportion of patients with LQT1-linked KCNQ1 mutations do not have abnormal QTc prolongation known as latent LQT1. Interestingly, exercise can reveal abnormal QTc prolongation in these patients. During exercise, beta-adrenergic activation stimulates PKA to phosphorylate Kv7.1, causing an increase in IKs to prevent ventricular AP prolongation. Therefore, the second aim of this dissertation was to determine a molecular mechanism of latent LQT1 through functional analyses in HEK293 cells while incorporating pharmacological and phosphomimetic approaches to study PKA regulation of mutant Kv7.1 channels.
The findings in this dissertation provide new insight into how KCNQ1 mutations disrupt the function of Kv7.1 in a basal condition or during beta-adrenergic activation. Also, this dissertation suggests these approaches will improve patient management by identifying mutation specific risk factors for patients with KCNQ1 mutations.
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Vasconcelos, Luiz Henrique César. "A ação relaxante do flavonoide 4',5,7-triidroxi-3,6-dimetoxiflavona, isolado de Piptadenia stipulacea (Benth.) Ducke, envolve modulação positiva de canais de potássio e redução dos níveis citosólicos de cálcio em íleo de cobaia." Universidade Federal da Paraíba, 2013. http://tede.biblioteca.ufpb.br:8080/handle/tede/8066.
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Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Piptadenia stipulacea (Benth.) Ducke (Fabaceae) is a typical tree of Caatinga, popularly known as “jurema-branca”, “jurema-malícia-da-serra”, “carcará” and “calumbi” and is popularly used as heling agent and antiinflamatory. From its aerial parts was isolated the flavonoid 4’,5,7-triidroxi-3,6-dimetoxiflavona (FGAL) that, in previous studies, inhibited both CCh- and histamine-induced phasic contractions on guinea pig ileum. Thus, the aim of this work was to characterize its relaxant mechanism of action. Isotonic and isometric contractions were recorded to determine and compare the relative efficacy and potency. The myocites viability was measured by the MTT assay, and the cytosolic Ca2+ levels by the analysis of fluorescence of fluo-4. The flavonoid relaxed the ileum pre-contracted with KCl 40 mM (EC50 = 2.6 ± 0.5 x 10-6 M) or CCh 10-5 M (EC50 = 1.8 ± 0.4 x 10-6 M), being more potent when the ileum was pre-contracted with histamine 10-6 M (EC50 = 1.9 ± 0.4 x 10-7 M). In addition, the flavonoid righward shifted the cumulative concentration-response curves of histamine in a non-parallel manner, with maximum effect (Emax) reduction, presenting a profile of non-competitive pseudoirreversible antagonism. To verify if FGAL would inhibit the Ca2+ influx through the voltage-sensitive Ca2+ channels (CaV), cumulative concentration-response curves of CaCl2 in depolarizing medium (70 mM KCl) nominally without Ca2+ were obtained in both the absence (control) and presence of different concentrations of FGAL. The flavonoid righward shifted the CaCl2 contraction curves in a non-parallel manner, with Emax reduction. Moreover, FGAL relaxed the pre-contracted ileum with S-(-)-Bay K8644 (3 x 10-7 M), a CaV1 agonist, but with lower potency than with KCl or histamine, indicating an indirect blockade of these channels. Then, in order to verify whether FGAL would be positivelly modulating the K+ channels to, indirectally, block the CaV1, it was employed CsCl, a non-selective K+ channels blocker. The relaxant potency of FGAL was attenauted in the presence of CsCl (EC50 = 1.1 ± 0.3 x 10-6 M) suggesting the involvement of these channels on this relaxant effect. In contrast, the relaxant potency of FGAL was not modified in the presence of apamin, SKCa blocker (EC50 = 1.6 ± 0.3 x 10-7 M), or TEA+ 1 mM, BKCa blocker (EC50 = 2.0 ± 1.0 x 10-7 M), discarding the participation of these subtypes of K+ channels. However, in the presence of 4-AP, KV blocker (EC50 = 1.8 ± 0.2 x 10-6 M), and glibenclamide, KATP blocker (EC50 = 1.5 ± 0.5 x 10-6 M), the relaxant potency of FGAL was attenuated about 10 and 8 times, respectively, confirming that FGAL positivelly modulates these subtypes of K+ channels to relax the guinea pig ileum. In the cellular experiments, the viability of intestinal myocytes was not altered in the presence of FGAL (10-4 M). Furthermore, the fluorescence intensity emmited by fluo-4 of myocytes stimulated with histamine was attenuated by FGAL as a result of [Ca2+]c reduction. Therefore, the relaxant mechanism of action of FGAL on guinea pig ileum involves the positive modulation of KV and KATP, which, indirectly, reduces the Ca2+ influx through CaV1, leading to the reduction of the cytosolic levels of this ion.
Piptadenia stipulacea (Benth.) Ducke (Fabaceae) é uma árvore típica da Caatinga, conhecida popularmente como “jurema-branca”, “jurema-malícia-da-serra”, “carcará” e “calumbi” e é popularmente utilizada como cicatrizante e anti-inflamatório. De suas partes aéreas foi isolado o flavonoide 4’,5,7-triidroxi-3,6-dimetoxiflavona (FGAL) que, em estudos anteriores, inibiu as contrações fásicas induzidas por carbacol (CCh) ou por histamina em íleo de cobaia. Diante disso, o objetivo deste trabalho foi caracterizar seu mecanismo de ação relaxante. As contrações isotônicas e isométricas foram monitoradas para determinar e comparar a eficácia e a potência relativas. A viabilidade dos miócitos do íleo foi medida utilizando o ensaio de MTT, e os níveis de Ca2+ citosólicos por meio da análise de fluorescência do fluo-4. FGAL relaxou o íleo pré-contraído com 40 mM de KCl (CE50 = 2,6 ± 0,5 x 10-6 M) ou com 10-5 M de CCh (CE50 = 1,8 ± 0,4 x 10-6 M), sendo mais potente quando o íleo foi pré-contraído com 10-6 M de histamina (CE50 = 1,9 ± 0,4 x 10-7 M). Além disso, o flavonoide deslocou para a direita as curvas concentração-resposta da histamina, de maneira não paralela com redução do efeito máximo (Emax), apresentando um perfil de antagonismo não competitivo pseudoirreversível. Para verificar se FGAL inibiria o influxo de Ca2+ pelos canais de cálcio dependentes de voltagem (CaV), foram obtidas curvas concentração-resposta cumulativas ao CaCl2 em meio despolarizante (KCl 70 mM) nominalmente sem Ca2+ na ausência (controle) e na presença de diferentes concentrações de FGAL. O flavonoide deslocou as curvas de contração do CaCl2 para a direita de maneira não paralela com redução do seu Emax. Além disso, FGAL relaxou o íleo pré-contraído com 3 x 10-7 M de S-(-)-Bay K8644, agonista dos CaV1, porém com menor potência do que com KCl ou histamina, indicando um bloqueio indireto desses canais. Assim, para verificar se FGAL modularia positivamente os canais de K+ para, indiretamente, bloquear os CaV1, utilizou-se o CsCl, bloqueador não seletivo dos canais de K+. FGAL teve sua potência relaxante atenuada na presença desse bloqueador (CE50 = 1,1 ± 0,3 x 10-6 M), sugerindo a participação desses canais no seu efeito relaxante. Diferentemente, a potência relaxante de FGAL não foi alterada na presença de apamina, bloqueador dos SKCa (CE50 = 1,6 ± 0,3 x 10-7 M), ou de TEA+ 1 mM, bloqueador dos BKCa (CE50 = 2,0 ± 1,0 x 10-7 M), descartando-se a participação desses subtipos de canais de K+. No entanto, na presença de 4-AP, bloqueador dos KV (CE50 = 1,8 ± 0,2 x 10-6 M), e de glibenclamida, bloqueador dos KATP (CE50 = 1,5 ± 0,5 x 10-6 M), a potência relaxante de FGAL foi atenuada cerca de 10 e 8 vezes, respectivamente, confirmando que FGAL modula positivamente esses subtipos de canais de K+ para relaxar o íleo de cobaia. Nos experimentos celulares, a viabilidade dos miócitos intestinais não foi alterada na presença de FGAL (10-4 M). Além disso, a intensidade de fluorescência emitida pelo fluo-4 complexado ao Ca2+ dos miócitos estimulados com histamina foi atenuada por FGAL, indicando que o flavonoide reduz a [Ca2+]c. Assim, o mecanismo de ação relaxante de FGAL em íleo de cobaia envolve a modulação positiva dos KV e dos KATP, o que, indiretamente, reduz o influxo de Ca2+ pelos CaV1, levando à redução dos níveis citosólicos desse íon.
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Montpetit, Marty L. "Functional Remodeling of the Cardiac Glycome Throughout the Developing Myocardium." [Tampa, Fla] : University of South Florida, 2008. http://purl.fcla.edu/usf/dc/et/SFE0002303.
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Araújo, Rúbia Aparecida de. "Molecular actions of pyrethroids on ion channels in the maize weevil, Sitophilus zeamais." Thesis, University of Nottingham, 2010. http://eprints.nottingham.ac.uk/11604/.
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Previous studies on the mechanism of action of pyrethroids have confirmed that voltage-gated sodium channels (VGSC) in the axon membrane are the major target site of these compounds. The use of pyrethroids to control maize weevils, Sitophilus zeamais, a major pest of stored maize in Brazil, has led to the occurrence of resistance. The work described here seeks to establish whether changes in VGSC of S.zeamais can explain pyrethroid resistance. The S. zeamais homologue of the Drosophila para VGSC was identified using degenerate primers and sequenced. Resistance mutations were examined by sequencing the IIS4-IIS6 region of the gene from laboratory strains of susceptible and resistant insects, revealing one amino acid replacement (T929I). The T929I mutation has been identified in other insects but always associated with a second mutation together producing a highly resistant phenotype. The occurrence of T929I in isolation is rare. DNA-based diagnostic assays were designed to screen weevils for the T929I mutation and analyse Brazilian field populations revealing a low frequency of heterozygous individuals carrying the mutation. The effect of the T929I mutation on VGSC function was investigated using whole cell patch clamping on cultured neurons isolated from thoracic ganglia of wild-type and resistant weevils. Inward currents were recorded by depolarizing the neuron to test potentials in the range -70mV to +70mV in 10mV increments for 25ms from a holding potential of -80mV. Current amplitudes were similar in cells from resistant weevils however other changes were apparent, notably a significant depolarizing shift in the voltage-dependence of activation of sodium currents in the resistant animals (P<0.05). Mutant neurons are also less sensitive to deltamethrin than the wild types.
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Buckler, K. J. "Actions of adrenergic agonists on transmembrane ion exchanges in skeletal and heart muscle." Thesis, University of Newcastle Upon Tyne, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.380754.
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Sharma, Kripa. "Bilevel Equalizer Drivers for Large Lithium-Ion Batteries." University of Toledo / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1564677943667852.
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Joulié, Marion. "Mécanisme de dissolution de matériaux actifs d'électrodes de type LiNi1/3Mn1/3Co1/3O2 d'accumulateurs Li-ion en vue de leur recyclage." Thesis, Montpellier, Ecole nationale supérieure de chimie, 2015. http://www.theses.fr/2015ENCM0011/document.
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La voie hydrométallugique représente une alternative pour la récupération des métaux de valeur tels que le nickel et le cobalt contenus dans les batteries Li-ion usagées. La première étape du procédé hydrométallurgique, l'étape de lixiviation a été optimisée grâce à l'étude du comportement du matériau actif d'électrode positive LiNi1/3Mn1/3Co1/3O2 (NMC) qui s'avère être le candidat idéal pour les batteries de véhicules électriques. Tout d'abord, l'étude des aspects thermodynamiques de la réaction de dissolution a permis de prédire le comportement du NMC dans divers acides. Puis, l'approche cinétique a conduit à l'élucidation du mécanisme se produisant lors de l'étape de lixiviation et à la mise en évidence de l'étape cinétiquement déterminante de la dissolution. Ce mécanisme a par la suite été généralisé aux autres matériaux couramment rencontrés dans les batteries Li-ion. L'impact d'agents réducteurs minéraux, organiques et métalliques pour promouvoir la dissolution du NMC a été évalué. Cette approche compare l'effet de réactifs à faible (acides sulfurique et chlorhydrique) et fort (acides citrique, oxalique et formique et peroxyde d'hydrogène) pouvoir réducteur ainsi que celui du cuivre et de l'aluminium provenant des collecteurs de courants des batteries Li-ion. Cette étude soulève le fort intérêt de l'emploi des collecteurs de courant présents de manière inhérente dans la fraction traitée par hydrométallurgieBasic hydrometallurgical routes represent an alternative to recover valuable metals such as nickel and cobalt from spent Li-ion batteries. The first step of hydrometallurgical process, lixiviation step is optimized by studying the behaviour of LiNi1/3Mn1/3Co1/3O2 (NMC) positive electrode active material, due to its good performances which make it an adequate candidate for the electric vehicles. First of all, the study of thermodynamic aspects allows predicting the behaviour of NMC material in various acidic media. Then, the kinetic approach leads to define the mechanism occurring during the leaching step and to outline the rate-limiting step of the dissolution. The reductive effect of mineral, organic and metallic reducing agents to promote leaching of NMC material is evaluated. The approach comparatively evaluates the reducing power impact of weak (sulfuric and hydrochloric acids), strong reducing agents (citric, oxalic and formic acids and hydrogen peroxide) and copper and aluminum from Li-ion batteries current collectors. This work points out the strong interest to advantageously use current collectors inherently present in the fraction treated by hydrometallurgy
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Santos, Renato Brito Moreira dos. "Development of electrospun Ion jelly fibers® for drug delivery." Master's thesis, Faculdade de Ciências e Tecnologia, 2011. http://hdl.handle.net/10362/6593.
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Dissertação para obtenção do Grau de Mestre em
BiotecnologiaThe aim of this work was the development of a drug delivery system based on Ion Jelly fibers. Ion Jelly (IJ) is a highly versatile polymeric material and is the result from the combination of gelatin and an ionic liquid (IL). For that purpose, different IJs were created using ILs based on choline and active pharmaceutical ingredients. The ILs used were choline acetate ([Ch][Ac]), choline mandelate([Ch][Ma]), choline tiglate ([Ch][Ti]) and choline ibuprofenate([Ch][Ib]). IJ fibers for drug delivery systems were produced through electrospinning, owing to its ability of producing polymeric fibers with reduced diameters and high surface area. The aim of this approach was to overcome the low diffusion rate that the above ILs exhibit due to their high viscosity. The impacts of electrospinning parameters on fiber production were evaluated. We verified that the most important parameter to achieve defect-free and thin IJ fibers was IL concentration. Morphological studies of IJ electrospun fibers were performed through optical microscopy and scanning electron microscopy. It was observed that IJ - [Ch][Ib] yielded slightly thinner fibers when compared with IJ-[Ch][Ti] fibers. The results from antibacterial tests using mandelic acid, [Ch][Ma] and IJ-[Ch][Ma] fibers as antibacterial agents against Escherichia coli K-12 and Bacillus subtilis T-168 prove that[Ch][Ma] encapsulation in IJ electrospun fibers greatly increased the IL properties. In addition,toxicological data suggest that the ILs studied were not toxic with the exception of [Ch][Ib] which shows a similar toxicity to crystalline ibuprofene. In addition, tensile tests suggest that water content has an important impact on both IJ mechanic behavior and elasticity. Additionally, we also evaluated the fabrication of IJ fibers using other polymers beyond gelatin, namely DNA and N,N-Dimethylchitosan. Nevertheless, no fibers were obtained.
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ALMEIDA, J. R. "Avaliação da composição química do material ativo do cátodo de baterias de íon-Lítio exauridas após lixiviação com ácido cítrico e análise por ICP OES." Universidade Federal do Espírito Santo, 2017. http://repositorio.ufes.br/handle/10/7345.
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Previous issue date: 2017-03-27Baterias de íon-Lítio (LIBs) exauridas são consideradas resíduos sólidos perigosos devido à presença de metais e compostos orgânicos em sua composição, representando desperdício de recursos naturais não renováveis e de metais valiosos quando descartadas. Este trabalho tem por objetivo fornecer dados quantitativos sobre a composição química do material ativo do cátodo (MAC) de diferentes LIBs exauridas visando monitorar variações com o passar dos anos e auxiliar nos processos de reciclagem do material. Os elementos Al, Co, Cr, Cu, Ga, Li, Mg, Mn, Ni, Ti e Zn foram determinados por espectrometria de emissão óptica com plasma indutivamente acoplado (ICP OES) após lixiviação ácida empregando 2,0 mol.L-1 de ácido cítrico (HCit) e H2O2 (0,25 mol.L-1) como alternativa ambientalmente favorável. As condições otimizadas para adequação do meio às curvas analíticas foram: para Al, Cu: Curva de HCit diluído 10 vezes sem padrão interno (PI); para Co, Li, Mn, Ni: Curva de HCit diluído 500 vezes sem PI; para Ga, Zn: Curva de HCit diluído 10 vezes com Y. O procedimento analítico empregado alcançou limites de detecção de 0,01 mg.L-1 para Al; 0,20 mg.L-1 para Co; 0,006 mg.L-1 para Cr; 0,02 mg.L-1 para Cu; 0,004 mg.L-1 para Ga; 0,02 mg.L-1 para Li; 0,0005 mg.L-1 para Mg; 0,07 mg.L-1 para Mn; 0,70 mg.L-1 para Ni; 0,0005 mg.L-1 para Ti e 0,007 mg.L-1 para Zn. A exatidão do procedimento foi confirmada por testes de adição e recuperação dos analitos obtendo-se valores entre 92-113 %. Os elementos majoritários Co (43-67 % m/m), Li (5,3-6,8 % m/m), Mn (0,8-8,2 % m/m), Ni (0,1-11,7 % m/m) e Al (0,06-3,2 % m/m) e os elementos minoritários Cr (0,0005-0,002 % m/m), Cu (0,01-0,05 % m/m), Mg (0,005-0,02 % m/m), Ti (0,001-0,07 % m/m), Ga (0,0009-0,03 % m/m) e Zn (0,009-0,05 % m/m) demonstraram que a composição do MAC pode variar de acordo com a capacidade e ano de fabricação. As baterias mais antigas foram as que apresentaram maiores teores de Co e Li. As baterias de menor capacidade foram as que continham os maiores teores de Mn e Ni, indicando que o Co foi substituído. O pó do MAC e o resíduo após lixiviação foram caracterizados por difratometria de raios X (DRX) obtendo-se LiCoO2 como composto principal, podendo ser reutilizado.
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Vieira, Goncalves Leonam. "Mechanisms of virucidal action of alcohol and metallic ions against nonenveloped viruses." Thesis, Cardiff University, 2018. http://orca.cf.ac.uk/111705/.
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Studying the mechanism of action (MoA) of biocides against pathogenic microorganisms is crucial to understand their efficacy and limitations, and to develop more efficient microbicidal formulations. Combining alcohol and zinc has been reported to enhance microbicidal activity, but the reasons for such activity are unknown. This study focuses on the impact of combining ethanol and zinc salt at pH 10.5 against nonenveloped viruses. The study is focused on three different aspects: i) virucidal activity screening of ethanol:zinc combinations against bacteriophages and human viruses; ii) impact of ethanol:zinc combinations on virus structure, particularly the viral capsid and nucleic acid, using Transmission Electron Microscopy (TEM); Atomic Force Microscopy (AFM) and agarose gel DNA electrophoresis and iii) chemical speciation and stability of ethanol:zinc combinations over time. The combination of ethanol with zinc salt was found to be more effective against viruses than control formulations containing sole active ingredients and/or excipients only. Activity test of 40%(w/v) ethanol with 0.1% (w/v) zinc salt with excipients (RB- 002 formulation) against F116 and adenovirus type 2 (AdV2) at 60 min contact time yielded 0.68 ± 0.02 and 5.26 ± 0.10 log10 reduction, respectively. In comparison, 0.1% (w/v) zinc salt only with excipient (RB-002G formulation) showed no virucidal activity against bacteriophage F116 (0.14 ± 0.02 log10 reduction) and AdV2 (0.80 ± 0.12 log10 reduction) in suspension. Differences between activities against bacteriophage MS2 and poliovirus type 1 were similar as the ones found between F116 and AdV2. Formulation containing 40%(w/v) ethanol with 0.1% (w/v) zinc salt produced a range of structural damage to F116 and attP AdV5 indicating possible capsid alteration. Effect of the combined formulation on viral capsid was confirmed with AFM with a possible decreased in virus capsid stiffness and significant virus capsid height reduction over 10 min contact time. F116 DNA damage was detected upon exposure to 40%(w/v) ethanol with 0.1% (w/v) zinc salt with excipients, but no damage was detected on AdV2 DNA through electrophoresis analysis. The alcohol/zinc formulation system at pH 10.5 was shown to have promising virucidal activity against non-enveloped viruses at room temperature following an alteration of the viral capsid, and possible damage to the viral nucleic acid. This study also showed the limitations of using bacteriophage as surrogate for mammalian viruses.
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Minian, Elías Gabriel. "Generalized cofribration categories and global action." [S.l. : s.n.], 1999. http://deposit.ddb.de/cgi-bin/dokserv?idn=957616961.
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Cabelguen, Pierre-Etienne. "Analyse de la microstructure des matériaux actifs d'électrode positive de batteries Lithium-ion." Thesis, Université Grenoble Alpes (ComUE), 2016. http://www.theses.fr/2016GREAI069/document.
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Ce travail de thèse se base sur quatre matériaux modèles, de composition LiNi1/3Mn1/3Co1/3O2, qui différent de par leur microstructure. Le lien entre leur morphologie et les performances électrochimiques est étudié par la combinaison de la caractérisation exhaustive de leur microstructure, l’étude de leur comportement en batterie et la modélisation de leur réponse électrochimique. L’étape limitant le processus électrochimique est identifiée par voltampérométrie cyclique et nous montrons que la transition attendue d’une limitation par le transfert de charge à une limitation par la diffusion en phase solide a lieu à différents régimes selon la microstructure. Ce comportement est expliqué par l’utilisation d’outils de simulations numériques. Selon leur forme et leur agglomération, les cristallites agissent collectivement ou indépendamment les unes des autres. Ces résultats rationalisent les performances en puissance obtenues sur nos matériaux. Les résultats de simulation montrent également qu’une faible fraction de la surface développée est électroactive, ce qui remet en question la large utilisation de la surface BET dans la littérature. Nous montrons également que, si les matériaux poreux sont les plus performants en puissance gravimétrique, la tendance est inversée pour la puissance volumique. Les stratégies de nanostructuration largement employées, qui se basent sur la capacité spécifique pour caractériser les matériaux, ne doivent pas oublier faire oublier le compromis nécessaire entre surface développée et volumeFour NMC materials are synthesized by co-precipitation. They exhibit a hierarchical architecture made of reasonably spherical agglomerates. One is constituted of flake-shaped, spatially oriented, crystallites that leave large apparent void spaces in the agglomerate, while the other results from the tight agglomeration of micron-sized cuboids. Porous material exhibits the best power performances. It is impossible to identify a geometrical parameter that predict performances, even after achieving the full characterization of the microstructures. Cyclic voltammetry reveals two behaviours depending on the shape of crystallites: processes limited by solid-state diffusion (cuboids) and the ones limited by charge transfer even at high rates (flake-shaped). This observation challenges active materials design strategies that assume diffusion as the limiting process of lithium intercalation. Focusing on enhancing kinetics could be the way to increase performances. Charge-transfer is first investigated by measuring electronic conductivities over a wide range of frequencies, allowing to discriminate relaxations arising at various length scales. We show that flake-shaped crystallites facilitate the motion of electrons at all scale levels compared to cuboids. Charge-transfer limitations originate from the electrolyte/material interface in materials exhibiting high surface areas. Numerical simulations reveal that BET measurements largely overestimate the actual electroactive surface, which is understood by HRTEM images of flake-shaped crystallites. Only a small percentage, limited to the edge plane is truly electroactive
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Chi, Lei. "COMPETITIVE DYNAMICS IN ELECTRONIC NETWORKS - ACHIEVING COMPETITIVENESS THROUGH INTERORGANIZATIONAL SYSTEMS." Lexington, Ky. : [University of Kentucky Libraries], 2005. http://lib.uky.edu/ETD/ukybuad2005d00316/ChiETD05.pdf.
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Thesis (Ph. D.)--University of Kentucky, 2005.Title from document title page (viewed on November 1, 2005). Document formatted into pages; contains ix, 143 p. : ill. Includes abstract and vita. Includes bibliographical references (p. 133-142).
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Lozenko, Sergii. "Heavy metal ion sensors based on organic microcavity lasers." Phd thesis, École normale supérieure de Cachan - ENS Cachan, 2011. http://tel.archives-ouvertes.fr/tel-00744846.
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Monitoring of environmental pollutants present at low concentrations requires creation of miniature, low-cost, and highly sensitive detectors that are capable to specifically identify target substances. In this thesis, a detection approach based on refractive index sensing with polymer micro-lasers is proposed and its application to the detection of heavy metal pollutants in water (mercury - Hg2+, cadmium - Cd2+ and lead - Pb2+) is studied. The resonance frequencies of the microcavity are highly sensitive to the refractive indices of the resonator surrounding: the resonances shift by a small amount when the surface refractive index changes, resulting from the interaction of the mode evanescent field with the surrounding medium. This permits label-free detection by coating the resonator with a suitable recognition species. The originality of this work lies in the utilization of active microcavities, or microlasers, created of the dye-doped polymers. Active microcavities offer an enhanced signal/noise ratio as compared to the passive ones and very narrow resonance peaks even at moderate quality factors (Q ≥- 6000). The choice of polymers as an active medium is connected with a number of advantages they offer: as opposite to semiconductors, polymers can be easily functionalized, integrated in microfluidic circuits and are cheaper in processing. Moreover, the use of porous polymer matrices may allow accumulation of analyte ions inside the microcavity and thus enhance the sensitivity. Two possible applications of microlasers are investigated in the thesis: refractive index variation sensing with non-functionalized cavities and heavy metal ion detection with functionalized cavities. In the first case, the sensitivity values have been obtained, comparable with the reported in literature for planar passive microresonators. In the second case, the experimental proofs of specific detection of mercury ions in liquid are presented. The ways of sensitivity improvement are discussed and verified and a foundation is layed for the creation of integrated Lab-on-Chip microfluidic biochemical detector.
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Rheault, Mark Ronald O'Donnell Michael J. "Transport of organic cations and anions by the isolated Malpighian tubules of insects." *McMaster only, 2005.
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Bunkóczi, Gábor. "Structure determination of peptides with antimicrobial action." [S.l. : s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=974033650.
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Kerdja, Youcef. "Caractérisation 3D et modélisation multi-échelle des matériaux actifs de batteries." Thesis, Université Grenoble Alpes, 2020. http://www.theses.fr/2020GRALI033.
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Quatre matériaux actifs de batteries Li-ion de type NMC (LiNi1/3Mn1/3Co1/3O2) ayant la même composition chimique, mais des microstructures différentes ont été synthétisés puis mis en œuvre sous forme d’électrodes composites afin de quantifier l’impact de la microstructure sur leurs performances électrochimiques. La tomographie FIB-SEM a été utilisée afin d’imager ces différentes microstructures. Les résultats 3D obtenus sur deux de nos matériaux permettent de montrer le lien entre tortuosité ionique et capacités en décharge. Des images 2D de ces microstructures ont été également extraites afin d’aller au-delà des mesures de tortuosité et de réaliser des simulations multi-physiques à l’échelle microstructurale sur des structures réelles d’électrodes. En parallèle, un modèle de simulations électrochimiques sur microstructures de matériaux d’électrodes a été développé. Ce dernier a permis dans un premier temps, via une étude paramétrique sur les propriétés physiques des matériaux, de visualiser sur une ‘microstructure modèle’, les mécanismes et les conditions par lesquels la diffusion de lithium (liquide et solide) et la cinétique électrochimique influencent la capacité en décharge et les hétérogénéités de lithiation au sein de la microstructure modèle. Les compétitions entre les différents mécanismes ont été également visualisées et quantifiées. Dans un deuxième temps, le modèle développé a été mis en œuvre sur deux des microstructures réelles (2D) extraites auparavant afin de simuler des décharges galvanostatiques. Cette démarche permet de suivre operando le courant local, ainsi que la surtension aux interfaces des particules de matériau actif au cours des décharges galvanostatiques. L’accès à ces grandeurs permet d’expliquer le biais par lequel ces deux électrodes de même composition chimique et de microstructures différentes présentent des capacités expérimentales en décharge différentesFour NMC type materials having the same chemical composition (LiNi1/3Mn1/3Co1/3O2) but different microstructures were synthesized and then used as positive electrodes to probe the impact of the microstructure over their electrochemical performances. FIB-SEM tomography was used to get 3D images of the synthesized materials, compute their ionic tortuosity and link the results to the observed electrochemical performances. 2D microscopy images were also obtained on the four materials to go beyond tortuosity computation and realize multi-physics simulations at the microstructure scale on real electrodes. To that end, an electrochemical model at the microstructure level has been developed. This model allows the visualization of the electrochemical kinetics’ as well as lithium liquid and solid diffusion’s influences over the global battery capacity and lithiation heterogeneities at the microstructure level. This study was performed, via a sensitivity analysis of the material physical properties, on a ‘template microstructure’ and allowed us to understand and quantify the different influences’ mechanism and the competition between them over the characteristics of the battery at multiple scales. After that, the developed model was used to simulate galvanostatic discharges on two of the previously extracted 2D microstructures. These simulations allowed us to get a real-time visualization of the local current density as well as of the overpotential at active material-electrolyte interface. The real-time visualization helped us to explain how two NMC type materials having the same chemical composition, but different microstructures led to different discharge capacities
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Mubenga, Ngalula Sandrine. "A Lithium-Ion Battery Management System with Bilevel Equalization." University of Toledo / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1513207337549147.
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Serra, Peinado Carla. "Papel del citoesqueleto de actina en la regulación de la H+-ATPasa vacuolar de complejo de Golgi." Doctoral thesis, Universitat de Barcelona, 2014. http://hdl.handle.net/10803/663846.
Full textAbstract:
La vía secretora se caracteriza por la acidificación progresiva de sus orgánulos, este gradiente es crucial para funciones tales como la modificación postraduccional de proteínas o el trafico de membranas. El principal responsable de generar y mantener este gradiente es la H+-ATPasa vacuolar (V-ATPase), que transporta protones desde el citosol hacía el interior del Golgi. Esta bomba está compuesta de dos dominios, el dominio V1 y el V0, a su vez ambos están formados por varias subunidades. Se ha descrito que las subunidades B y C del dominio V1 contienen dominios de unión a actina.
Existen significantes similitudes entre los efectos subcelulares producidos por la despolimerización de actina y la inhibición farmacológica de la V-ATPasa: Alteración de transporte vesicular Golgi-Retículo endolplasmatico y Golgi-membrana plasmática, alcalinización del complejo de Golgi, dilatación de las cisternas de Golgi. Teniendo en cuenta que dos subunidades de la V-ATPasa tienen la capacidad de unirse a los microfilamentos de actina, nosotros hipotetizamos que estos podrían participar en la homeostasis del pH de Golgi a través de la regulación de la V-ATPasa, particularmente la actina podría estar manteniendo la asociación de los dominios V1 y V0.
Generamos un constructo de la subunidad B conjugado con GFP (B2-GFP) que se incorporaba en el dominio V1. Observamos que este constructo se localizaba en los compartimentos distales del complejo de Golgi y que translocaba al citosol al despolimerizar la actina. Diferentes ensayos bioquímicos nos sirvieron para confirmar que la despolimerización de actina inducía la disociación de los dominios V1 y V0 de la V-ATPasa. Además, detectamos interacción entre la actina y las subunidades B y C. Finalmente, está descrito que la V-ATPasa se localiza en los dominios ricos en colesterol de la membrana plasmática y que el citoesqueleto de actina juega un papel importante en la organización de estos dominios, lo que observamos fue que la desorganización de los dominios ricos en colesterol inducía una subida del pH de Golgi.
Con todo, concluimos que la actina regula el pH de Golgi a través del mantenimiento de la asociación de los dos dominios de la ATPasa gracias a su unión a las subunidades B y C además de su papel en el mantenimiento de los dominios ricos en colesterol.We previously reported that agents that depolymerize actin filaments promote the alkalization of the Golgi stack and the trans-Golgi network. Vacuolar-type H-translocating ATPase (V-ATPase) is responsible of proton translocation and acidification of Golgi lumen. V-ATPase is a multisubunit complex composed of two domains (V1 and V0). Moreover, two subunits of V1 domain contain actin binding sides, subunit B and C. In this work we hypothesize that actin filaments could have a role in the maintaining of V1 and V0 domain association. We have generated a GFPtagged subunit B2 construct that is incorporated into the V1 domain, this construct localizes at distal Golgi compartments and translocate to cytosol upon actin depolymerization. Several biochemical assays confirmed that microfilaments distruption induces dissociation of V1-V0 domains. Moreover, we detected interaction between subunits B-C and actin filaments. Finally, V-ATPase is localized in lipid raft domains of plasma membrane and actin filaments participate in organization of these domains. We observed that lipid raft disorganization promotes an increase of intra-Golgi pH. Overall, we conclude that actin regulates the Golgi pH homeostasis maintaining the coupling of V1-V0 domains of V-ATPase through the binding of microfilaments to subunits B and C and preserving the integrity of lipid raft.
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Bandla, Venkat Nehru. "Modeling the internal inhomogeneous aging behavior in large-format commercial Li-ion batteries." Thesis, Amiens, 2018. http://www.theses.fr/2018AMIE0027/document.
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Les batteries Li-ion (LIB) sont utilisées comme dispositifs de stockage d'énergie dans les applications automobiles, mobiles ou stationnaire. Cependant, leur vieillissement conduisant à une dégradation de leur performance reste un problème majeur. Les LIB présentent un comportement non uniforme qui entraîne une utilisation incomplète et un vieillissement non uniforme. L'objectif de ce travail est donc d'identifier les facteurs influençant le comportement inhomogène et d'étudier leur effet sur le vieillissement. Une approche combinée modèle/expérimentation est adoptée. Un dispositif expérimental a été développé pour simuler les dispersions thermiques et de potentiels dans les batteries Li-ion commerciales. Ce dispositif est utilisé pour effectuer des tests en cyclage et le vieillissement inhomogène est évalué par des tests de caractérisation effectués pendant et après le cyclage. Des modèles multi-physiques décrivant le comportement des LIB ont été développés pour représenter le comportement du système expérimental. Deux phénomènes de vieillissement identifiés expérimentalement sont pris en compte, à savoir la formation d'une couche de SEI (Solid Electrolyte Interface) et la perte de matière active d'électrode positive. Le premier est fortement dépendant de la température et le second est plus uniforme. Cette approche combinée a permis de montrer que la dispersion thermique avait plus d'impact que les différences de potentiel sur l'homogénéité du vieillissementLi-ion batteries (LIB) are used as energy storage devices in automobile, mobile and stationary applications. However their lifetime issue is a primary concern resulting in a decreased performance. Li-ion batteries exhibit non-uniform behavior that results in incomplete utilization of the cell energy and non-uniform aging. Thus the objective of this work is to identify the factors influencing the inhomogeneous behavior and to study their effect on aging. A combined modeling and experimental approach is adopted in this work. In the experimental work, a setup is developed that surrogates the thermal and potential gradients occurring in commercial LIB. This setup is used to perform long-term accelerated cycling tests and inhomogeneous aging behavior is assessed. Several characterization tests are performed during and after the completion of the cycling. In the modeling part, multiphysics models describing the electrochemical, electrical and thermal behavior of LIB are developed. These models are appropriately coupled integrated with an aging component to represent the experimental setup behavior. Two main degradation phenomena, namely SEI (Solid Electrolyte Interface) formation and positive electrode active material have been identified experimentally and modelled. The latter is uniform whereas the former is influenced by temperature. Based on this, thermal dispersion impact on the inhomogeneity is greater than potential dispersion