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1
DʹAngelo, Donna Jean. "Mechanisms governing phosphorus retention in streams /." This resource online, 1990. http://scholar.lib.vt.edu/theses/available/etd-08252008-162550/.
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D'Angelo, Donna Jean. "Mechanisms governing phosphorus retention in streams." Diss., Virginia Tech, 1990. http://hdl.handle.net/10919/39241.
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Vogan, Kyle J. "Mechanisms governing DNA recognition by murine Pax-3." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape10/PQDD_0020/NQ44620.pdf.
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Tsang, Bernie Pui Man. "Modelling of the mechanisms governing crimp in wool." Thesis, University of Canterbury. Mathematics and Statistics, 2003. http://hdl.handle.net/10092/7921.
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This thesis considers modelling one of the mechanisms, which governs the formation of wool fibres. The problem is investigated by constructing a mathematical model that is based on the geometry of the ultrastructure of the wool fibres. The deformed shapes of the wool fibres are obtained by minimising the strain energy calculated from the mathematical model. The objective of this study is to explore the relationship between the ultrastructure and the crimpy shape of the wool fibres.
The first chapter gives the background information of wool fibre, the outline of the thesis and defines the problem.
The second chapter examines the structures inside the wool fibres and the mechanisms, which govern the shapes of the wools fibres. The variables used to describe the fibre shapes are introduced here. Then, some simple examples are given to demonstrate the mathematical model.
In the third chapter, the structures of the wool fibres are simplified with several assumptions and used to construct the basic model. Then, some results are given with various values of different parameters to demonstrate the properties of the model. Some modifications of the model are made, which include the addition of the cuticle shell and an approximate analytical model by Taylor's expansion.
The fourth chapter develops another modification of the mathematical model with the addition of a 'macrofibril' structure. The fifth chapter gives the last modification of the model uses integration to calculate the total energy of the whole fibre.
The sixth and the seventh chapters show the practical methods to measure the natural shape of a single fibre and the cross-section pattern of the fibre respectively. The measured natural shape of the wool fibre can be used to verify the local estimated shape of the wool fibre, which is calculated by the mathematical model with the measured cross-section pattern.
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Davidowitz, Rachel Alexis. "Mechanisms Governing Mesothelial Clearance by Ovarian Cancer Spheroids." Thesis, Harvard University, 2013. http://dissertations.umi.com/gsas.harvard:10719.
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Metastatic dissemination of ovarian tumors involves the invasion of multi-cellular tumor cell clusters into the mesothelial cell lining of organs in the peritoneal cavity. We developed an in vitro assay that models this initial step of ovarian cancer metastasis to investigate the mechanisms of invasion. Pre-clustered ovarian cancer multicellular spheroids are incubated with GFP-expressing mesothelial monolayers and the extent of mesothelial invasion is monitored by time-lapse video microscopy.
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Burleigh, Angela. "Regulatory mechanisms governing mammary epithelial and progenitor cell growth." Thesis, University of British Columbia, 2011. http://hdl.handle.net/2429/35593.
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The processes involved in mammary gland development are intimately linked with
those that drive breast oncogenesis. Regulation of growth, tissue polarity and genome
stability are a few of the factors the maintain homeostasis in breast epithelium and prevent
malignant progression. In this work, a series of clonal 184-hTERT cell lines were generated
that modeled the in vitro growth characteristics of bi-potent mammary progenitor cells; they
were dependent upon fibroblasts for low-density growth and formed dual-lineage acini in 3D
culture. These lines were subsequently used in a genome-wide siRNA screen to identify the
factors that regulate fibroblast-driven epithelial cell growth. Fibroblasts constitute the
majority of cells within stroma, which plays a major role in supporting mammary progenitor
cell growth. From this screen, 49 surface and secreted factors were identified that putatively
transduce the signals emanating from the fibroblasts that are required for epithelial cell
growth. These factors were more potent than any of the previously described growth factor
receptors. When assessed in primary tissue, Gpr39, Scarb2, Ntn1, Efna4, Nptx1, and Ctnna1
were found to have the greatest effect on overall progenitor cell growth, while SerpinH1
differentially suppressed luminal progenitor cells, and Nkain4 and Kcnj5 differentially
suppressed bi-potent progenitor cells. Further profiling of these lines identified the planar
cell polarity protein Celsr1 as differentially regulated under fibroblast-dependent conditions.
Silencing of Celsr1 increased the number of bi-potent progenitor cells detected in the colonyforming
assay. Furthermore, it induced branching morphogenesis within normally spherical
acini and disrupted the apical polarity of these structures in 3D culture. Within this system,
Celsr1 is suspected of signaling through Shisa4. This is the first description of a noncanonical
Celsr1 interactor. Finally, a curious variant line was identified amongst the
collection of 184-hTERT cells generated for this work. This line harbours mitotic spindle
and cell cycle checkpoint defects, and rapidly gains chromosome 20 during passaging.
Through an elimination process, de novo promoter hypomethylation and subsequent
overexpression of CENPI was identified as likely being responsible for this phenotype. This
is the first description of CENPI deregulation and one of a few descriptions of gene promoter
hypomethylation resulting in genome instability.
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Cameron, Angus James MacGregor. "Molecular mechanisms governing Fc#gamma# receptor mediated signal transduction." Thesis, University of Glasgow, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.340327.
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Riel, Bruno J. "Mechanisms governing the growth of self-assembled quantum dots." Thesis, University of Ottawa (Canada), 2002. http://hdl.handle.net/10393/6448.
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We produced self-assembled quantum dot (QD) samples of InAs on GaAs by molecular beam epitaxy (MBE). With these, we explored growth effects as a function of InAs coverage for three arsenic pressures, and as a function of arsenic pressure at a specific InAs coverage. During growth, the samples were studied using reflection high energy electron diffraction (RHEED). These RHEED measurements were compared to low energy electron diffraction (LEED) measurements. To perform this ex-situ LEED characterisation, some samples were covered with an amorphous arsenic cap. This cap was thermally evaporated producing a clean, non-oxidised surface that was studied using LEED. We obtained non-ambiguous identification of the GaAs (001) surface reconstructions as well as timing information for the 2D to 3D transition during the growth of InAs on GaAs. Post growth characterisation of two sets of self-assembled QD samples, twelve samples in all, revealed the following: As a function of increasing the arsenic pressure used in QD growth, the photoluminescence (PL) of capped QDs is first redshifted at low arsenic pressures, and then blueshifted at high arsenic pressures. Scanning electron microscopy and atomic force microscopy of uncapped QDs show that as the arsenic pressure increases, the QD density increases while the average QD width and height decrease monotonically; these trends are consistent with the shift in PL for the high arsenic pressure samples, but are inconsistent with the shift in PL for the low pressure samples. This leads us to proposing a mechanism by which QDs may be modified as they are overgrown with capping material. We discuss the effects of adjusting the arsenic pressure on the formation of QDs and the mechanism by which QDs may be modified during capping.
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Grav, Torstein. "Mechanisms Governing the occurrence of Partial Discharges in Insulation Liquids." Thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for fysikk, 2013. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-22385.
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Breakdown of electrical equipment is unwanted and the use of reliable methods of insulation are therefore necessary. Liquid insulation is one preferred material for electrical devices used in subsea installations due to outstanding qualities related to insulation, heat transfer, safety and incompressibility properties. To ensure that the selected insulating liquid is suitable for the specific equipment it will be necessary to test its insulating quality. This is verified by stressing the liquid with voltages higher than the partial discharge inception voltage (PDIV). While there are existing tests for these properties, such as use of partial discharge measurements, this thesis examines an experimental approach to testing the properties of different liquids in a point-plane gap through the use of high AC voltage.Charges, like ions, in an electrical field creates a current flow. In a liquid, dissociative ionization under applied voltage is the mechanism that generates the most charges. Field emission originating from the negative polarity contributes in some liquids. Moving charges in the liquids results in measurable currents of the order 10 - 80 nA under applied AC voltage of 20 kV$_{peak}$ in a 20 mm point-plane gap in different liquids. Space charges are also found to affect the partial discharge (PD) behaviour in liquids. Different liquids have different chemical and physical properties and therefore different PD behaviour. It has been observed that PDs are stochastic, and in some sense correlated to earlier stress due to residual ions from previous half periods and permanently change of the chemical structure of some liquid molecules after a PD. The PD rate increases exponentially with increasing voltage, while the maximum charge per half period tends to increase linearly. This observed behaviour is in agreement with what is found in earlier reports.The presence of free electrons is important. A significant increase in the rate of PD at low magnitudes in both polarities occurred when the test cell was exposed to X-rays. PDs start under the influence of a strong field or an electron avalanche. It is essential to be able to test different liquids in laboratory conditions, for economical reasons, in order to identify the most suitable insulating media. Power electronics utilizing quality insulation is more reliable with a lower probability of downtime. The test setup and methods used in this thesis may easily be adapted for test of electrical components and equipment instead of the simple point-plane gap method.Different liquids have different PD phase patterns. This thesis intends to describe the reasons to explain this difference. It is found to be the result of different properties in the liquids for charge creation and differences in their electrical field threshold for PD initiation. PDs of a certain size are rarely occurring events and are strongly dependent on the prehistory of the stressed liquid gap. We do not know whether PDs in itself is harmful to insulating properties or not. It is therefore uncertain whether the IEC 61294 test method, based on PDs, provides any useful information or not. More research is therefore needed in order to fully understand the PD phenomenon.
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Scotto, Mark Vincent. "Mechanisms governing the abatement of metal emissions from waste incineration." Diss., The University of Arizona, 1992. http://hdl.handle.net/10150/186079.
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A naturally occurring sorbent, kaolinite, is injected into a down-flow pilot scale combustor burning natural gas, doped with a surrogate metal containing waste (usually lead acetate). When sorbent is not introduced, lead vaporized in the flame ultimately forms a unimodal particle size distribution centered at approximately 0.1 μm., often referred to as fume. The injection of sorbent prevents the formation of this fine particulate, by reactively scavenging the lead as vapor above its dewpoint temperature. The approximately 1 μm lead alumina-silicate particles formed capture nearly 100% of the lead, yet yield very low water soluble lead mass fractions. Thus, lead is chemically fixed in particles that are approximately an order of magnitude larger in size than the lead aerosol fume. Consequently, air pollution control systems can capture these particles relatively efficiently, and the metal's isolation from the environment is ensured when subsequently disposed of in a landfill. Chlorine is a commonly occurring halogen in many incinerable waste streams. With increasing Cl/Pb ratio, the mass fraction of lead captured decreases. At a chlorine gas injection rate resulting in a Cl/Pb ratio of 2/1, 10/1, and 17/1, the obtained mass fraction of lead captured was 79.7%, 44.0%, and 37.8%. The uncaptured lead remained in the gas phase as the relatively volatile PbCl₂, which formed a water soluble fume upon temperature quench in the sampling probe. These results indicate that sorbent injection could be less effective at metal capture for incinerable waste streams with both chloride and metal fractions. A multi-component aerosol simulations package (MAEROS) is utilized to model the temporal evolution of a lead aerosol particle size distribution in the combustor. Base case simulations model the Pb-O₂ system, and accounts for homogeneous nucleation, physical condensation, and coagulation. These simulations match the data fairly well under conditions which promote self nucleation (i.e. steep temperature profiles). The MAEROS model is also utilized to simulate the Pb-O₂-sorbent and Pb-O₂-Cl₂-sorbent systems in an attempt to elucidate the lead capture mechanisms. Also, the model-fitted intrinsic reaction rates are much greater than the rates obtained from the lead/sorbent bench scale experiments from the literature.
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Herbert, Francis William. "Mechanisms governing the growth, reactivity and stability of iron sulfides." Thesis, Massachusetts Institute of Technology, 2015. http://hdl.handle.net/1721.1/98126.
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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Materials Science and Engineering, 2015.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (pages 135-140).
The kinetics of electrochemical processes in ionic materials are fundamentally governed by dynamic events at the atomic scale, including point defect formation and migration, and molecular interactions at the surface. A corrosion system comprising an iron sulfide film (passive layer) formed on iron or steel in contact with an hydrogen sulfide (H₂S)- rich fluid can thus, in principle, be modeled by a series of unit reaction steps that control the rate of degradation under given thermodynamic conditions. This overarching thesis goal necessitates a concerted experimental and computational approach to determine the relevant kinetic parameters such as activation barriers Ea and rate constants v₀ for the homogeneous and heterogeneous reactions of interest. These fundamental values can be obtained experimentally via temperature-dependent measurements on pure, model iron sulfide samples. This thesis therefore consists of three case studies on the stable Fe-S phases pyrrhotite (Fe₁-xS) and pyrite (FeS₂) to identify the elementary corrosion mechanisms and their kinetic parameters. Pyrrhotite is of interest because the off-stoichiometry of this phase leads to relatively rapid bulk processes such as diffusion; pyrite has a comparitively inert bulk but this work showed that it has a chemically labile surface. The first study focuses on two basic, rate-controlling steps in the growth of pyrrhotite: cation diffusion and sulfur exchange at the surface. First, iron self-diffusivity *DFe is determined across the temperature range 170-400 °C through magnetokinetic studies of the diffusion-driven "[lambda]" magnetic transformation, as well as direct tracer diffusion measurements in Fe₁-xS crystals using secondary ion mass spectrometry (SIMS). This range encompasses the sponteneous magnetic and structural order-disorder temperature TN = 315 °C in pyrrhotite. The effect of spontaneous magnetization below TN is to increase the Fe vacancy migration energy by a combined 40% increasing Ea for diffusion from 0.83 eV in paramagnetic Fe₁-xS to ~1.20 eV in the fully magnetized state. An extrapolation of the Arrhenius law from the paramagnetic regime would therefore overestimate actual diffusivities by up to 10² times at 150 °C. Second, the surface exchange of sulfur from H₂S into the solid state in Fe₁-xS is measured using electrical conductivity relaxation, yielding Ea = 1.1 eV for sulfur incorporation into pyrrhotite. With their similar thermal dependence, there is no clear temperature crossover from cation diffusion- to surface exchange-limiting regimes, or vice versa. Instead, surface exchange is expected to constrain pyrrhotite growth for films under ~100 [mu]m thickness, beyond which diffusion becomes the rate limiting mechanism, independent of external driving factors such as temperature. The second study explores the role of surface electronic states on the electrochemical reactivity of pyrite. Charge transfer between a solid surface and an adsorbate such as H₂S requires the mutual availability of filled/empty electronic states at the same energy level. The semiconducting FeS₂(100) surface is predicted to have intrinsic surface states (SS's) from Fe and S dangling bonds, as well as extrinsic SS's related to delocalized defects at the surface, both of which would affect charge transfer characteristics. A novel, broadly-applicable methodology is developed in this thesis to quantify the energy and density of these SS's, based on experimental scanning tunneling microscopy / spectroscopy (STM/STS) in conjunction with first principles tunneling current modeling. As a result, a decreased surface band gap Eg of 0.4 eV, compared to 0.95 eV in bulk pyrite, is measured. The findings highlight the need to differentiate between bulk and surface electronic structure when assessing heterogeneous reactivity, and have implications for the use of FeS₂ in potential technological applications, for example as a photovoltaic adsorber. Finally, the dynamics of point defect formation and clustering on FeS₂(100) under high-temperature, reducing conditions are investigated to understand the stability of the surface under extreme conditions. Synchrotron x-ray photoelectron spectroscopy (XPS) is used to measure a formation energy [delta]Hf for sulfur vacancies in the topmost atomic layer of 0.1 eV up to approximately 240 °C. Above this temperature, however, point defects are shown to condense into surface pits as measured by scnaning tunneling microscopy (STM). The combined, experimental XPS and STM results are replicated with high precision by a kinetic Monte Carlo (kMC) simulation, developed by Aravind Krishnamoorthy towards his doctoral thesis, of surface degradation on realistic length-and timescales of 10-¹⁰ - 10-⁷ m and up to several hours, respectively. The findings have implications for the initiation of surface breakdown via pitting in ionic passive films, as well as providing a broader understanding of the non-stoichiometry of the pyrite surface. The common thread is a focus on events at the atomic and electronic scale, with an emphasis on point defects. The results thereby facilitate a bottom-up approach to modeling electrochemical processes such as corrosion in Fe-S phases, in which the unit steps are cast into probabilistic simulation tools. While the three studies here comprise only a partial examination of the atomic-scale events regulating the behavior of Fe-S passive layers, this approach makes inroads towards more accurate component lifetime prediction and the design of robust materials for aggressive environments. Moreover, the fundamental surface and bulk physical chemistry of iron sulfides explored in this work has implications beyond corrosion to other uses of these materials, including potential magnetic devices (Fe₁-xS) and earth-abundant photovoltaic and photoelectrochemical adsorbers (FeS₂).
by Francis William Herbert.
Ph. D.
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Fok, Ezio T. "Uncovering the hidden mechanisms governing the transcriptional regulation of inflammation." Doctoral thesis, Faculty of Health Sciences, 2021. http://hdl.handle.net/11427/32667.
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Inflammation provides broad immunological protection that is essential for our survival. This cellular response is characterised by a biphasic cycle consisting of an initial acute pro-inflammatory phase and a subsequent resolving anti-inflammatory phase. Underlying each of these phases are changes in the expression of hundreds of immune genes, which encode for inflammatory mediators called cytokines. Importantly, the biphasic nature of inflammation requires cytokine expression to be highly regulated and coordinated to different timescales during each phase of inflammation. For the initial proinflammatory response, cytokine expression needs to be rapid and robust to efficiently initiate host defence mechanisms and provide effective immunological protection. In contrast, the expression of anti-inflammatory cytokines is temporally delayed to ensure that anti-inflammation always follows pro-inflammation. In order to choreograph the expression of these cytokines during inflammation, numerous mechanisms within the cell serve to regulate and coordinate cytokine transcription. Within the eukaryotic nucleus, multiple modes of transcriptional regulation function cooperatively to provide the regulatory capacity that is required for complex transcription patterns to emerge. These include the organisation of the genome, which confine cognate chromosomal contacts that are causal to transcription, and long-non coding RNAs (lncRNAs) that function to discretely fine tune transcriptional activity. Although many of the mechanisms that regulate transcription have been well described, their role in cytokine expression during inflammation remains largely unknown. In particular, the mechanisms that facilitate rapid and robust cytokine expression during proinflammation and the regulatory networks that coordinate the biphasic regulation of inflammation are unresolved. In this work, two novel lncRNAs were discovered to transcriptionally regulate these key features of cytokine expression during inflammation. The first, UMLILO (Upstream Master LncRNA of the Inflammatory chemokine LOcus), was found to emanate from the ELR+ CXCL chemokine TAD and regulate the transcriptional activation of the pro-inflammatory ELR+ CXCL chemokines (IL-8, CXCL1, CXCL2 and CXCL3). By exploiting the pre-formed local 3D topology, UMLILO is able to epigenetically prime the chemokines for transcriptional activation. This involves the discrete deposition of H3K4me3 onto the promoters of the chemokines, which allows for the pre-loading of transcriptional machinery prior to their signal-dependent activation. This reveals a fundamental mechanism for the epigenetic priming and rapid activation of pro-inflammatory cytokine genes. The second lncRNA, called AMANZI (A MAster Non-coding RNA antagoniZing Inflammation), was found to coordinate the transcription of two functionally opposed cytokines: the master pro-inflammatory IL-1β and the broad antiinflammatory IL-37. AMANZI is encoded in the promoter of IL-1β, which results in its concomitant expression when IL-1β is transcriptionally active. Functionally, AMANZI mediates the formation of a dynamic chromosomal contact between IL-1β and IL-37. This leads to the delayed transcriptional activation of IL-37 ensuring that the pro-inflammatory function of IL-1β precedes IL-37 mediated anti-inflammation. This revealed a novel biphasic circuit that coordinated the expression of IL-1β and IL-37, through the activity of AMANZI, to regulate the two functionally opposed states of inflammation. Clinical observations in healthy individuals revealed that a polymorphism occurring in AMANZI (rs16944) was able to augment the state of this genetic circuit and shift the relative levels of IL-1β and IL-37 to influence an individual's inflammatory capacity. This affected the establishment of innate immunological memory, which is involved in the progression of many inflammatory conditions and the efficacy of certain vaccines. The work described here uncovers novel mechanisms that transcriptionally regulate key features of the inflammatory response. Importantly, this work implicates the role of two novel lncRNAs in inflammation, essentially contributing to the functional annotation to the genome and providing novel targets for the modulation of pathogenic inflammation.
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Havrda, Matthew C. "Molecular Mechanisms of Notch Signaling Governing Vascular Smooth Muscle Cell Proliferation." Fogler Library, University of Maine, 2006. http://www.library.umaine.edu/theses/pdf/HavrdaMC2006.pdf.
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Glund, Stephan. "Molecular mechanisms governing contraction-induced metabolic responses and skeletal muscle reprogramming /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-436-5/.
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Mwabe, Philip Ogwari. "Mechanisms governing alkali metal capture by kaolinite in a downflow combustor." Diss., The University of Arizona, 1993. http://hdl.handle.net/10150/186425.
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Experimental work was carried on a 17 kW, 600 cm long, gas fired laboratory combustor to investigate the post flame reactive capture of alkali species by kaolinite. Emphasis was on alkali/sorbent interactions occurring in flue gas at temperatures above the alkali dewpoint and on the formation of water insoluble reaction products. Time-temperature studies were carried out by injecting kaolinite at different axial points along the combustor. The effect of chlorine and sulfur on alkali capture was investigated by doping the flame with SO₂ and Cl₂ gases to simulate coal flame environments. Particle time and temperature history was kept as close as possible to that which would ordinarily be found in a practical boiler. Experiments designed to extract apparent initial reaction rates were carried using a narrow range, 1-2 μm modal size sorbent, while, a coarse, multi size sorbent was used to investigate the governing transport mechanisms. The capture reaction has been proposed to be between alkali hydroxide and activated kaolinite, and remains so in the presence of sulfur and chlorine. The presence of sulfur reduces sodium capture by under 10% at 1300°e. Larger reductions at lower temperatures are attributed to the elevated dewpoint of sodium sulfate (∼850°C) with subsequent reduction in sorbent residence time in the alkali gas phase domain. Chlorine reduces sodium capture by 30% across the temperature range covered by the present experiments. This result has been linked to thermodynamic equilibria between sodium hydroxide, sodium chloride and water. An optimum temperature window between 900°C-1100°C, in which the formation of water insoluble alkali alumino silicates is favored, has been reported. Above 1200°C the sorbent used here, melted. Sorbent melt at such low temperatures is probably due to the impurities (Ti, Fe, K) in kaolinite. A simple first order kinetic model is proposed for sodium capture by metakaolinite and is best fitted by volume rate k = 4.5±0.5x10⁷ exp (-5300±150 kcal/RT) cm³ gas/ cm³ porous solid.sec. Activation energies in the range of 6-10 kCal/mol gave model prediction results that compared very well with experimental data. Kinetics is the rate controlling mechanism for small particles under 3.00μ with intraphase pore diffusion shown to be the controlling mechanism for particles larger than 3 μm. A maximum sorbent utilization of 50% was realized.
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Glaros, Trevor Griffiths. "Molecular Mechanisms Governing Persistent Induction of Pro-Inflammatory Genes by Lipopolysaccharide." Diss., Virginia Tech, 2011. http://hdl.handle.net/10919/73001.
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Low dose endotoxemia is caused by several health conditions including smoking, alcohol abuse, high fat diets, and aging. Several studies have correlated low dose endotoxemia with increased risks of atherosclerosis, diabetes, and Parkinson's disease. Unlike high doses of endotoxin which induce a strong but transient induction of pro-inflammatory mediators, low doses of endotoxin result in a mild but chronic induction of pro-inflammatory genes. The central hypothesis of our study was that if low doses of endotoxin are capable of inducing mild prolonged inflammation, then a unique signaling circuit must be utilized.
In the first study, the molecular mechanisms for the persistent induction of lipocalin 2 (LCN2) in response to 100 ng/mL of lipopolysaccharide (LPS) in kidney fibroblasts was examined. It appears that the intracellular signaling network responsible for the persistent induction of LCN2 requires both activator protein-1 (AP-1) and CCAAT/enhancer binding protein delta (C/ebpδ). Interleukin-1 receptor-associated kinase 1 (IRAK-1) is critical for LCN2 expression.
In the second study, the molecular mechanisms governing the persistent induction of interleukin 6 (IL-6) upon a 50 pg/mL challenge of LPS in macrophages was examined. At this dose, only the persistent activation of cJun N-terminal kinase (JNK) and C/ebpδ was observed. IL-6 transcription requires the transient recruitment of activating transcription factor 2 (ATF2) and the persistent recruitment of C/ebpδ to the IL-6 promoter.
In the third study, the molecular mechanisms that mediate LPS-induced priming was examined. The results demonstrate that macrophages are able to sense their prior history of exposure to LPS that result in either a priming or tolerance phenotype upon a secondary challenge of LPS. Results suggest that this sensing mechanism involves cross-talk between IRAK-1 and phosphoinositide-3-kinase (PI3K).
Collectively, these studies indicate that JNK and C/ebpδ are the primary players responsible for the persistent expression of pro-inflammatory genes during low dose endotoxemia. IRAK-1 is a key intracellular signaling kinase that mediates signaling at low doses of LPS. IRAK-1 is not only critical for low dose induced expression, but also for LPS-induced priming. This research has revealed a novel signaling pathway that could provide new molecular targets for drug development against chronic inflammatory diseases.Ph. D.
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Egriboz, Onur. "THE MOLECULAR MECHANISMS GOVERNING THE GAL GENE SWITCH OF SACCHAROMYCES CEREVISIAE." The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1338319985.
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Irazoki, Oihane. "Elucidation of the RecA-mediated mechanisms governing swarming motility in Salmonella enterica." Doctoral thesis, Universitat Autònoma de Barcelona, 2017. http://hdl.handle.net/10803/405518.
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RecA es una proteína multifuncional que, aparte de ser la recombinasa principal implicada en los pasos cenrrales de la recombinación homóloga y en los mecanismos de reparación de DNA,también es el activador de la respuesta SOS.RecA actúa como sensor de lesiones en el DNA.Al unirse a DNA monocarenario, la proteína se activa (RecA*)y promueve la auto-hidrólisis del represor lexA,induciendo asíla expresión de los genes de la respuesta SOS.Además,se ha descrito que la proteína RccA está también vinculada con la motilidad en enjambre.
El movimiento en enjambre o swarming, que está. ampliamente distribuido en el dominio Bacteria, se defin.e como una translocación multicelular rápida y organiz.ada de lasbacterias sobresuperficies sólidas o semi.sólidasmediada por la rotación Aagclar. Varios estudios asocian la proteína RecA con CheW, un componente davc en el ensamblaje de los quirniorrecepcores y de las matrices de señalización formadas por éstos, queson.esenciales para el swarming.
los resultadospresentados en la presente Tesis Doctoral demuestran inequívocamente la interacción entre RecA y CheW. En el desarrollo de éste trabajo se ha caracterizado el complejo RecA-CheW, permitiendo la identificación de las interfaces
crúicas implicadas en la interacción entre ambas proteín.as y su papel en la forrn.ación de las matrices de señalización . Además, se han podido identificar como esenciales para la interacción los residuos Gln20,Arg222,Argl 76 y Lys250 de RecA,que se encuentran en.losdomin.ios esttucmrales N-terminal ycentral de dicha proteína,y los residuos Phe21,Lys55,
Asp83 y Phe121 de CbeW,que por dónde se ubican no parecen interferir con ninguna otra región de unión descrita para ChcW.
Además, los experimentos realizados demuestran que la pérdida de swarming es consecuencia de la disrupción de las matricesde seúalización generada por el aumemo en la concentración innacelular de la proteína RecA.Los ensayos llevados a cabo mediante microscopía de alta resolución, han permitido rasnear la distribución i nnacelular de las proteínas CheW
y RecA durante la inducción de la respuesta SOS,y elucidar el papel de la proteína RecA en.la distribución de CheW y en
el ensamblajedelasmatrices de sef1alización.
Final meme, los resultados obre.nidos permiten proponer un modelo que explica cómo las células bacterianas adaptan su motilidad sobre superficies en respuesta a la presencia de agentes nocivos para el DNA mediante la detección de ésrns a través. de la induccióndel sis.tema SOS. Durantela coloniz.ación desuperficies,lascélulas bacterianas pueden estar expuestas
a una amplia gama de compuestos dañinosy poten.dalm.ente letales. Sin embargo, las células pueden eludirlos gracias a la
inducción de la respuesta SOS y la consiguiente inhibición del swarmíng. Así, cuando concentraciones sub-letales de compuestos tóxicosgeneran lesionesen el DNA,la proteína RecA se activa induciendo la respuesta SOS, y,dado que recA es uno de Los primeros genesen lajerarquía de la activación SOS,su concen.tración aumenta rápidamence.Éste incremento de la concentración intracelular RecA perturba el equilibrio entre esta proteína y CheW,concretamente,RecA secuestra a la proteína CheW, evitando el correcto ensamblaje de las matrices de seña!i:?ación polar, causando el cese del movimiento swarmingcuando seinduce la respuesta SOS.Mediante este mecanismo ,las bacterias evitan la exposición a concentraciones mayores del agente nocivo,y por lo tanto, la muerte celular. Una vez se reparan las lesiones en el DNA dañado, la concentración de RecA decrece hasta su nivel basal, evitando el secue5tro de la proteína CheW, re5taurándose así el ensamblaje de las matrices quimiosensoriales y también el movimiento en enjanbre.Así pues, los daros presentados han permitido la caracterización del mecanismo molecular que gobierna la modulación de swttrming mediada por RecA, mediante d cualSafmoneüapuede adaptar su motilidad en superficie en respuesta a condiciones ambientales adversas.We characterized the RecA-CheW protein complex, that allowed the identification of the critical interfaces implied in the interaction and its role in the signaling array assembly. RecA residues Gln20, Arg222, Arg176 and Lys250 that are located in the multi-functional N-terminal and central structural domains of the protein, were described as essential for the interaction. In the case of CheW protein, residues Phe21, Lys55, Asp83 and Phe121 were involved in the RecA-binding, that do not seem to interfere with any other CheW-biding targets. Further, the obtained results demonstrate that the loss of swarming ability when there is an increase of RecA concentration was the consequence of chemosensing array assembly disruption, that previous works have established as essential for swarming in temperate swarmers. Using high resolution microscopy assays we were able to track CheW and RecA protein distribution within the cell during SOS response induction, elucidating the role of the RecA protein in the distribution of CheW and the assembly of chemoreceptor signaling arrays. The obtained results head to the proposal of a model that explains how bacterial cells adapt their surface motility in response to the presence of DNA-damaging agents by sensing them via SOS system induction. During surface colonization, bacterial cells will likely be exposed to a wide range of injurious, and potentially lethal, compounds that are avoided through SOS response induction and consequent swarming ability impairment. When DNA injuries are generated, RecA activates the SOS machinery, and its concentration rises swi��ly since recA is one of the first genes to be induced in the hierarchy of SOS activation. The increase of intracellular RecA concentration during SOS-response disturbs the equilibrium between this protein and CheW, causing the cessation of swarming. RecA prompts the titration of CheW protein, preventing polar signaling array assembly during SOS response, and thereby inhibiting motility. By this mechanism, bacteria avoid exposure to higher concentrations of the DNA damaging agent, and so, cell death. Following DNA damage repair, RecA concentration returns to its basal level, releasing CheW, that restores chemosensory array assembly, returning the cell to a non-DNA damage motile condition. Therefore, the present work characterizes the molecular mechanisms that govern RecAmediated swarming modulation, by which using RecA as a sensor, Salmonella cells can adapt their surface motility in response to adverse environmental conditions.
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Kompus, Kristiina. "How the past becomes present neural mechanisms governing retrieval from episodic memory /." Doctoral thesis, Umeå : Umeå university, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-31873.
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Comber, Kate. "Investigation into the molecular mechanisms governing Drosophila embryonic hemocyte migration in vivo." Thesis, University of Bath, 2014. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.606669.
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Accumulating evidence highlights the importance of studying the migration of cells within the context of their natural environment as manipulating the substrate on which a cell is migrating can have a dramatic impact on the mode/mechanisms employed by cells during migration. Central to this phenomenon is the requirement of adhesion to the ECM in order to gain traction during migration. Integrins constitute the main family of cell receptors involved in mediating cell-ECM interactions during motility. Whilst traditionally two-dimensional cell culture studies have placed emphasis on the importance of these receptors for spreading and migration, it has become evident that within more confined environments these receptors, at least for some cell types, are less crucial. In this research we utilise Drosophila embryonic hemocytes as an in vivo model for cell migration. We show that whilst hemocytes migrate within confined environments in vivo, these cells depend on integrins for powering both developmental and inflammatory migrations. Given the close association between these receptors and the actin cytoskeleton we were surprised to discover that removal of the main β integrin subunit, Myospheroid, did not affect cell spreading in vivo and had only a small impact on lamellipodial structure and dynamics. Furthermore we discovered that, in contrast to other cell types previously analysed, removal of this integrin subunit in hemocytes was not accompanied by an increase in the rate of actin retrograde flow within the protrusions, which we believe could reflect abrogation of a positive feedback between Rho, ROCK and Myosin II contraction. Instead, we discover a key role for integrins in regulating the microtubule cytoskeleton, in the maintenance of a polarised microtubule bundle, termed a ‘microtubule-arm’. Although the molecular mechanisms by which this stabilisation is coordinated have yet to be identified, this provides important insight into the co-regulation of adhesion and microtubule cytoskeleton important for the migratory behaviour of these cells. Cell migration reflects the complex and integrated regulation of the actin cytoskeleton by diverse families of actin regulatory proteins. Using hemocytes as a model system, we also explore the regulatory interactions between two main actin regulatory proteins, Diaphanous and Enabled, in vivo. Whilst the function of these proteins in the formation of filopodial protrusions is overlapping, recent research has highlighted the ability of these proteins to regulate the activity of one another. We find that co-expression of Enabled in hemocytes is able to rescue the morphological and migratory defects resulting from overexpression of active Diaphanous. Thus, data here presents Enabled as a negative regulator of Diaphanous, which may play an important role in the migration of hemocytes in vivo.
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McDonagh, Ellen Mary. "The molecular mechanisms governing the regulation of chemokine receptors CXCR3 and CXCR6." Thesis, Imperial College London, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.523747.
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zhu, zhenduo. "Mechanisms Governing the Eyewall Replacement Cycle in Numerical Simulations of Tropical Cyclones." FIU Digital Commons, 2014. http://digitalcommons.fiu.edu/etd/1389.
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Eyewall replacement cycle (ERC) is frequently observed during the evolution of intensifying Tropical Cyclones (TCs). Although intensely studied in recent years, the underlying mechanisms of ERC are still poorly understood, and the forecast of ERC remains a great challenge. To advance our understanding of ERC and provide insights in improvement of numerical forecast of ERC, a series of numerical simulations is performed to investigate ERCs in TC-like vortices on a f-plane. The simulated ERCs possess key features similar to those observed in real TCs including the formation of a secondary tangential wind maximum associated with the outer eyewall. The Sawyer-Eliassen equation and tangential momentum budget analyses are performed to diagnose the mechanisms underlying the secondary eyewall formation (SEF) and ERC. Our diagnoses reveal crucial roles of outer rainband heating in governing the formation and development of the secondary tangential wind maximum and demonstrate that the outer rainband convection must reach a critical strength relative to the eyewall before SEF and the subsequent ERC can occur. A positive feedback among low-level convection, acceleration of tangential winds in the boundary layer, and surface evaporation that leads to the development of ERC and a mechanism for the demise of inner eyewall that involves interaction between the transverse circulations induced by eyewall and outer rainband convection are proposed. The tangential momentum budget indicates that the net tendency of tangential wind is a small residual resultant from a large cancellation between tendencies induced by the resolved and sub-grid scale (SGS) processes. The large SGS contribution to the tangential wind budget explains different characteristics of ERC shown in previous numerical studies and poses a great challenge for a timely correct forecast of ERC. The sensitivity experiments show that ERCs are strongly subjected to model physics, vortex radial structure and background wind. The impact of model physics on ERC can be well understood with the interaction among eyewall/outer rainband heating, radilal inflow in the boundary layer, surface layer turbulent processes, and shallow convection in the moat. However, further investigations are needed to fully understand the exhibited sensitivities of ERC to vortex radial structure and background wind.
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Carrick, Sam. "The dynamic interplay of mechanisms governing infiltration into structured and layered soil columns." Lincoln University, 2009. http://hdl.handle.net/10182/1328.
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Worldwide there is considerable concern over the effects of human activities on the quantity and quality of freshwater. Measurement of infiltration behaviour will be important for improving freshwater management. This study identifies that New Zealand has a sporadic history of measuring soil water movement attributes on a limited number of soil types, although the current practical demand should be large for management of irrigation, dairy farm effluent disposal, as well as municipal / domestic waste- and storm-water disposal. Previous research has demonstrated that infiltration behaviour is governed by the interplay between numerous mechanisms including hydrophobicity and preferential flow, the latter being an important mechanism of contaminant leaching for many NZ soils. Future characterisation will need to recognise the dynamic nature of these interactions, and be able to reliably characterise the key infiltration mechanisms. Since macropores are responsible for preferential flow, it is critical that infiltration studies use a representative sample of the macropore network. The aim of this project was to study the mechanisms governing the infiltration behaviour of a layered soil in large (50 x 70 cm) monolith lysimeters, where the connectivity of the macropore network remains undisturbed. Four lysimeters of the Gorge silt loam were collected, a structured soil with four distinct layers. On each lysimeter there were four separate infiltration experiments, with water applied under suctions of 0, 0.5, 1, and 1.5 kPa by a custom-built tension infiltrometer. Each lysimeter was instrumented with 30 tensiometers, located in arrays at the layer boundaries. There was also a field experiment using ponded dye infiltration to visually define preferential flowpaths. Analysis of dye patterns, temporal variability in soil matric potential (Ψm), and solute breakthrough curves all show that preferential flow is an important infiltration mechanism. Preferential flowpaths were activated when Ψm was above -1.5 kPa. During saturated infiltration, at least 97% of drainage was through the ‘mobile’ pore volume of the lysimeter (θm), estimated among the lysimeters at 5.4 – 8.7 % of the lysimeter volume. Early-time infiltration behaviour did not show the classical square-root of time behaviour, indicating sorptivity was not the governing mechanism. This was consistent across the four lysimeters, and during infiltration under different surface imposed suctions. The most likely mechanism restricting sorptivity is weak hydrophobicity, which appears to restrict infiltration for the first 5 – 10 mm of infiltration. Overall, the Gorge soil’s early-time infiltration behaviour is governed by the dynamic interaction between sorptivity, hydrophobicity, the network of air-filled pores, preferential flow and air encapsulation. Long-time infiltration behaviour was intimately linked to the temporal dynamics of Ψm, which was in turn controlled by preferential flow and soil layer interactions. Preferential flowpaths created strong inter-layer connectivity by allowing an irregular wetting front to reach lower layers within 2 – 15 mm of infiltration. Thereafter, layer interactions dominate infiltration for long-time periods, as Ψm in soil layers with different K(Ψm) relationships self-adjusts to try to maintain a constant Darcy velocity. An important finding was that Ψm rarely attained the value set by the tension infiltrometer during unsaturated infiltration. The results show that ‘true’ steady-state infiltration is unlikely to occur in layered soils. A quasi-steady state was identified once the whole column had fully wet and layer interactions had settled to where Ψm changes occurred in unison through each soil layer. Quasi-steady state was difficult to identify from just the cumulative infiltration curve, but more robustly identified as when infiltration matched drainage, and Ψm measurements showed each layer had a stable hydraulic gradient. I conclude that the in-situ hydraulic conductivity, K(Ψm), of individual soil layers can be accurately and meaningfully determined from lysimeter-scale infiltration experiments. My results show that K(Ψm) is different for each soil layer, and that differences are consistent among the four lysimeters. Under saturated flow the subsoil had the lowest conductivity, and was the restricting layer. Most interestingly this pattern reversed during unsaturated flow. As Ψm decreased below -0.5 to -1 kPa, the subsoil was markedly more conductive, and the topsoil layers became the restricting layers. All four soil layers demonstrate a sharp decline in K(Ψm) as Ψm decreases, with a break in slope at ~ -1 kPa indicating the dual-permeability nature of all layers.
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Johnson, Christopher. "An analysis of the molecular mechanisms governing nitrogen metabolite repression in 'Aspergillus nidulans'." Thesis, University of Newcastle Upon Tyne, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.442318.
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Shimatani, Hiroyuki. "Identification of Common and Separate Mechanisms Governing Circadian Locomotor Activity and Body Temperature." Doctoral thesis, Kyoto University, 2021. http://hdl.handle.net/2433/263603.
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Ng, York Hunt. "Cadherin-linked molecular mechanisms governing the terminal differentiation of human trophoblastic cells in vitro." Thesis, University of British Columbia, 2010. http://hdl.handle.net/2429/27098.
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Background: The formation of the multinucleated syncytial trophoblast of the human placenta is a critical step in pregnancy, which is prone to failure. In these studies, I have examined the role of TWIST, a transcription factor identified as a key repressor of E-cad expression in normal and cancer cells of diverse origins, in the differentiation of human trophoblastic cells in vitro. The invasion of extravillous cytotrophoblasts (EVTs) into the underlying maternal tissues and vasculature is a key step in human placentation. The molecular mechanisms underlying the development of the invasive phenotype of EVTs include many of those first identified as having a role in cancer cell metastasis. In view of these observations, I have examined the expression, regulation, and function of Twist, Runx2 and N-cad in human trophoblastic cells in vitro.
Materials and Methods: Gain or loss-of-function studies were then performed to determine the role of Twist in terminal differentiation and fusion in these cells. The presence of multinucleated syncytium was confirmed by indirect immunofluorescence. Concentration- and time-dependent studies were performed to determine whether interleukin (IL)-1β and transforming growth factor (TGF)-β1 regulate Twist and Runx2 mRNA and protein levels in EVTs. Next, a siRNA strategy was employed to determine the role of Twist, Runx2 and N-cad in HTR-8/SVneo EVT cells.
Results: Exogenous expression of Twist resulted in a continuous and progressive decrease in E-cad expression and the subsequent formation of syncytium in BeWo cells maintained under normal culture conditions. In contrast, siRNA specific for Twist inhibited the cAMP-mediated differentiation of these cells over time in culture. The cytokines, IL-1β and TGF-β1, respectively induced the differential up- and down-regulation of Twist and Runx2 expression in primary cultures of EVTs in both a concentration and time-dependent manner. Use of a siRNA strategy demonstrated that a reduction in Twist, Runx2 or N-cad in HTR-8/SVneo cells concomitantly decreased the invasiveness of these cells.
Conclusions: Collectively, my findings demonstrate that TWIST is an upstream regulator of the E-CAD-mediated terminal differentiation and fusion of human trophoblastic cells in vitro. TWIST, RUNX2 and N-CAD are key molecules underlying the invasive capacity of EVTs.
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Ziegler-Purcell, Ulrike G. "Rheological mechanisms governing variation in the extent of gas cell expansion in bread dough." Thesis, University of Reading, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.250682.
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Baudoin, Camille. "Numerical evaluations of mechanisms governing the heat transport in the edge plasma of tokamaks." Thesis, Aix-Marseille, 2018. http://www.theses.fr/2018AIXM0053/document.
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La fusion nucléaire est une solution technologique prometteuse pour une nouvelle source d'énergie. Cependant, utiliser la par fusion nucléaire confinement magnétique comme source d'énergie constitue un challenge scientifique et technologique car cela requière à la fois un bon confinement du plasma de cœur et un contrôle des flux de chaleurs arrivant à la paroi. Ce travail est motivé par la problématique de la gestion des flux de chaleur dans les réacteurs de fusion. Cela est nécessaire pour éviter d'endommager les coûteux composants faisant face au plasma. La compréhension des mécanismes physiques régissant le transport de la chaleur dans le plasma de bord est une tâche critique pour le design des futures machines. Dans ce contexte, il est nécessaire de faire des prédictions fiables de l'étalement de la chaleur dans le but de dimensionner correctement ces futures machines. Cela appelle à un fondement théorique décrivant la manière dont l'énergie s'échappe du plasma. Des études théoriques et expérimentales ont tenté aboutir à cette fin, cependant les mécanismes en jeux ne sont toujours pas clairs. Pour atteindre ce but, la modélisation numérique est un complément nécessaire aux expériences. Ce travail de thèse est dédié à l'étude numérique des différents aspects du transport de la chaleur dans le plasma de bord un utilisant les approches fluides. Une attention particulière est porté à deux mécanismes suspectés de joué un grand rôle dans le transport de la chaleur : le transport intermittent due à la turbulence et le transport convectif à large échelle par les vitesses dérives. Le problème a été traité avec une approche graduelle en utilisant différent outils numériquesFusion devices are a promising solution for a new source of energy. However, using fusion reaction to produce power within a magnetic confinement is a scientific and technological challenge as it requires a high confinement in the core plasma at the same time as a good control of plasma exhaust on the material walls. This work is motivated by the key problematic of power handling in fusion power plants necessary to avoid damaging the expensive plasma facing components (PFC). The understanding of the physics underlying the heat transport, and more specifically is a critical task for the engineering design of future Tokamak devices. In this context, it is mandatory to make reliable predictions of the power spreading in order to correctly size the future Tokamaks. This calls for a theoretical ground describing the way energy escapes the core plasma through the separatrix and deposits on the PFCs. Some theoretical and experimental studies attempt to achieve such a task, however no definitive conclusion have been drawn yet. To achieve this goal, numerical modelling is a necessary complement to experimental results. This PhD work has been dedicated to the study of the different aspects of the heat transport in the edge plasma using a numerical fluid approach. Special focus was devoted to two types of mechanisms suspected to play an important role in the heat transport: intermittent turbulence; the large-scale convective transport
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Evans, Katherine J. "A quantitative analysis of the physical mechanisms governing the life cycles of persistent flow anomalies." Diss., Georgia Institute of Technology, 2000. http://hdl.handle.net/1853/26013.
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O'Connor, Caitlin M. "Mechanisms Governing the Tumor Suppressive Functions of the A-alpha Subunit of Protein Phosphatase 2A." Case Western Reserve University School of Graduate Studies / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=case1560175638682868.
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Lehain, Stephanie. "Molecular mechanisms governing CD4+ T cell recognition of human papilloma virus (HPV) E6 in cervical carcinoma." Thesis, Cardiff University, 2009. http://orca.cf.ac.uk/55812/.
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Genital human papillomavirus (HPV) infection is common and the majority of infected individuals successfully clear with this virus. But in less than 5% of the cases the infection by high-risk HPV induces cervical cancer, which is preceded by a phase of persistent HPV infection during which the host immune system fails to eliminate the virus. Effective eradication of HPV-positive tumours may require both CD8+ and CD4+ T-cell-mediated immune responses. Specific CD4 T cell responses against the protein E6 of the HPV16 have been described in healthy subjects, but appear absent in patients with cervical cancer. This suggests the importance of specific CD4+ T-cell responses against E6 protein for the clearance of the virus. The aim of this project was to investigate the molecular interactions involved in T cell recognition of the HPV16 E6127-141 (DKKQRFHNIRGRWTG) peptide, in particular, mapping the important amino acids for T cell receptor (TCR) and MHC contact. Initially, this was to be done directly by studying the biophysical interactions between soluble TCR and MHC molecules. Several constructs were made with the pBACgus expression vector in an attempt to generate soluble HLA-DR1/HPV16 E6127-141 complexes. These vectors were used to generate recombinant baculovirus to infect insect cells, but unfortunately no stable MHCipeptide complexes were expressed.. Since the biophysical approach was unsuccessful, the impact of changes in the peptide structure was assessed using functional T cell activation (IFN-gamma secretion). Two separate T-cell clones against HPV16 E6127-141 were tested against truncated versions of the peptide. The results show that the amino acids from the Cterminal end are essential for functional activation of both T-cell lines. Conversely, the amino acids from the N-terminal end do not appear to be as important. These variations in the responses induce by truncated peptides could be due to effects on TCR contact or MHC binding. However, molecular modelling of the HPV16 E6127-141 associated with the MHC complex suggests that the Cterminal end of the peptide contributes to MHC binding.. These two clones were tested against variants of HPV16 E6127-141 from different High risk HPV types (HPV31, 52, 33, 58, 67). Three types of response could be demonstrated. Indeed two peptides (HPV31, 52) have a null effect on the two T-cell clones, two others (HPV33, 58) have a partial agonist effect and one peptide (HPV67), has an antagonist effect on the T-cell clone. Based on these limited results, a model mechanism for viral immune evasion is proposed, whereby co-infection or sequential infection by different high risk HPV types could induce antagonistic effects on T cell responses. This could potentially inhibit effective clearance of a single HPV type, leading to viral persistence and disease.
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Mauser, Jonathon. "Regulatory Mechanisms Governing the Establishment of Cell Polarity and Mitotic Spindle Orientation in the Drosophila Neuroblast." Thesis, University of Oregon, 2014. http://hdl.handle.net/1794/18344.
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The Drosophila neuroblast undergoes repeated asymmetric cell divisions that produce one daughter cell that assumes a neuronal fate and another that remains a neuroblast. During mitosis, the neuroblast polarizes the conserved Par polarity complex to the apical cortex, which is responsible for segregating fate determinants to the basal cell cortex. Polarity is accompanied by orientation of the mitotic spindle through the proteins Pins, Mud, and Dlg to ensure that the cleavage furrow properly segregates the fate determinants. The adaptor protein Inscuteable coordinates these two pathways. In my work, I have addressed how asymmetrically dividing cells are dynamically polarized during the cell cycle and how the resulting polarity is coupled to spindle position.
To address how neuroblast polarity is dynamically controlled, I identified the protein Inscuteable as a continuously polarized cue for Par complex localization during mitosis. Inscuteable and Bazooka, a member of the Par complex, interact directly and form a complex that is regulated by the mitotic kinase Aurora A. Regulating this interaction allows for cell-cycle dependent establishment of polarity and for the subsequent loss of polarity after the cell divides.
To investigate how Par complex directed polarity is connected to spindle position, I investigated the effect of Inscuteable binding on the spindle orientation ability of the protein Pins. When bound to Inscuteable, Pins' spindle orientation activity becomes repressed. Inscuteable competes with Mud for Pins binding and represses the Gai-Pins-Mud signaling pathway. Function of the parallel Pins-Dlg pathway remains unaffected. This repression behavior may allow differential timing of spindle attachment (through Dlg) and spindle shortening (through Mud) pathways that ensures correct alignment of the mitotic spindle.
I was able to model the spindle orientation behavior of Pins using a synthetic protein containing activation sites that have different affinities for the activator. Changing the number and affinities of these activation sites leads to different response profiles that mimic the ultrasensitive behavior of Pins using a non-cooperative mechanism. Together, these regulatory mechanisms cooperate to allow for spatial and temporal control of polarity and for physical connection of polarity to the mitotic spindle.
This dissertation includes previously published and unpublished co-authored material.
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Platts, Lauren. "Molecular mechanisms governing the effects of arginine and other positively charged amino acids on protein thermal stability." Thesis, University of Sheffield, 2016. http://etheses.whiterose.ac.uk/17678/.
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Arginine is an amino acid that is used extensively as an excipient in therapeutic protein formulations due to its unique ability to solubilise proteins and prevent aggregation without negative effects on protein stability. However, the mechanisms by which it exerts these distinctive effects are still open to conjecture. It is also undecided as to whether arginine is capable of destabilising at least some proteins. A major problem with the existing data on arginine effects on protein stability is the lack of low concentration data, and the presence of salt-containing buffers. The major aim of this thesis was to establish whether arginine acts on protein stability as a combination of its two major functional groups: glycine and guanidinium hydrochloride (GdnHCl). These two molecules are well-known stabilisers and destabilisers respectively. A detailed thermal stability study of three globular proteins in the presence of these three cosolutes demonstrated that arginine affects protein stability as an additive combination of its two functional groups: glycine and GdnHCl, with mechanisms originating from both groups. This results in two stage concentration-dependent stability effects, with low cosolute concentrations (100 mM) causing less severe protein-specific effects. Lysine and histidine, the other positively charged amino acids are also shown to affect protein thermal stability via a combination of their respective functional groups. Glycine-GdnHCl mixtures are shown to also act on protein thermal stability similar to arginine, or in a synergistically stabilising manner (depending on the protein), meaning they have the potential to be developed as ‘designer excipients’ whereby bespoke ratios of the functional groups are used in place of arginine to exert the desired stability effects. Experimental evidence of arginine clustering is also presented, with head-to-tail electrostatic interactions and Gdn-Gdn self-association thought to be responsible. Although no link between clustering and protein stability effects are found.
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Weir, Marion. "Novel Mechanisms Governing Autoregulation of the Src Family Kinase Fyn and its Crosstalk with Protein Kinase A." ScholarWorks @ UVM, 2016. http://scholarworks.uvm.edu/graddis/592.
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ABSTRACT
Phosphorylation is a post-translational modification important for regulating protein activity and protein binding capacity. It is used in many different signaling pathways within the cell. Src Family Kinases and Protein Kinase A (PKA) are two prototyptical non-receptor tyrosine and serine/ threonine kinases, respectively, which are found in canonical signaling pathways. These two kinases are critical for signaling in essentially every cell of a multicellular organism, and are particularly important in development, cell migration and proliferation. Although both proteins have been intensely studied for many decades, an understanding of the molecular mechanisms which govern their regulation and the regulation that they effect on other proteins are still being elucidated.
Fyn, like its related Src Family Kinase members, has previously been shown to be regulated by two tyrosine phosphorylation events at residues Y420 and Y531. Y420 is located in the kinase (Src Homology 1(SH1)) domain and it is a highly-characterized intermolecular autophosphorylation site that increases the activity of the kinase. Y531 is located near the C-terminus and is phosphorylated by C-terminal Src kinase (Csk). Phosphorylation of Y531 allows it to bind to R176 in the SH2 domain in an intramolecular fashion. In this conformation Fyn has only basal activity. Since these sites are essential for regulating the activity of the kinase, we hypothesized that four novel sites of tyrosine phosphorylation in Fyn could also importantly regulate the protein. Three of the novel sites lie in the SH2 domain, and one is located in the kinase domain. Mass spectrometry, in vitro kinase assays, as well as western blot analysis aided in uncovering that these novel Fyn phosphorylation sites fine tune the activity and substrate binding of the protein.
PKA has been implicated in a multitude of signaling pathways and is particularly important in cell growth, proliferation, and migration. Fyn and PKA have classically been considered to be in separate signaling pathways. However, research over the past several decades has provided evidence that there is crosstalk that exists between the two pathways. The SFK Fyn and PKA can phosphorylate each other, thereby regulating each other's activity. Based on these data, we hypothesized the existence of downstream effectors of this relatively uncharacterized pathway. It was hypothesized that the presence of Fyn could lead to PKA activation and to differences in PKA binding partners. Through the use of co-immunoprecipitations, Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and quantitative mass spectrometry, many proteins were found to increase their binding to PKA in the presence of Fyn. Several proteins were selected and further biochemically validated. These data suggest that the presence of Fyn could allow for PKA to more importantly interact with discrete pools of proteins within the cell to effectuate its signal transduction. Together these studies provide understanding on critical and fundamental processes by which all cells function.
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Gale, Thomas Kenyon. "Mechanisms governing multi-species metal capture by kaolinite, hydrated lime, and novel sorbents in high-temperature combustion environments." Diss., The University of Arizona, 2001. http://hdl.handle.net/10150/280397.
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The objective of this work was to provide a solution to the problem of toxic metal emissions from high temperature combustion processes. Multi-metal as well as single-metal interactions were investigated to provide an understanding of mechanisms that exist in industrial furnaces, where multiple metals are present. Specifically, multiple toxic metals, lead and cadmium, and a common non-toxic metal, sodium, were investigated. Sodium capture by kaolinite was found to exhibit a negative activation energy (between 1100 and 1300°C) similar to that shown previously for lead, due to a catastrophic deactivating melt initiated by the metal oxide/kaolinite reaction product. In addition, an overall sodium/kaolinite reaction rate (soluble + insoluble) was determined. It was also discovered that a larger percentage of sodium/kaolinite reaction product was water soluble when formed at lower equivalence ratios than at high equivalence ratios. The majority of the initially formed sodium/kaolinite reaction products were probably insoluble sodium aluminosilicates. However, at high sorbent utilizations (low equivalence ratios), the meta-kaolinite structure probably broke down to form sodium silicates and aluminates, thus enabling at least twice as much sodium capture as the sodium aluminosilicate products. The cadmium/kaolinite reaction rate was highly activated between 1100°C and 1300°C, due to a self-enhancing melt, which occurred at the high but not low temperature condition. For the Cd/Pb multi-metal system, cadmium capture was enhanced by a melt initiated by the lead/kaolinite reaction product. Also, cadmium enhanced lead capture by reducing the extent of catastrophic melt caused by the lead/kaolinite product. The formation of an optimum eutectic melt accounts for the enhancement of total bimetal capture by kaolinite at high and low temperatures (1100°C to 1300°C). Sodium capture by kaolinite completely dominated over lead capture from a bimetal system. On the other hand, sodium was found to behave similar to lead in terms of enhancing cadmium capture by kaolinite at the low temperature condition. In addition to kaolinite, hydrated lime was found to be effective at capturing cadmium, and CDEM sorbent, composed of calcium carbonate, lime, and kaolinite, was effective at capturing cadmium and a mixture of cadmium and lead.
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Perignon, Mariela C. "Mechanisms governing avulsions in transient landscapes : analysis of the May 2006 Suncook River avulsion in Epsom, New Hampshire." Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/114334.
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Thesis: S.B., Massachusetts Institute of Technology, Department of Earth, Atmospheric, and Planetary Sciences, 2007.Cataloged from PDF version of thesis.
Includes bibliographical references (pages 60-66).
Avulsions, or rapid changes in the location of a river, usually occur in environments such as deltas, floodplains, and alluvial fans where net-deposition can raise the bed of the river above its floodplain. Avulsions are less frequent in transient landscapes, such as New England, where topography and hydrography are still responding to recent glaciation. One of these rare avulsions occurred during a 100-year flood on the Suncook River, Epsom, NH, between May 14 and 15,2006. We studied the Suncook River event to develop a model for the drivers of avulsions in transient landscapes. We suggest that a strong substrate in the parent channel, such as bedrock or immobile boulders, can facilitate an avulsion by preventing incision and driving water overbank. Easily erodible substrates in the path of the new channel can also contribute to avulsions by allowing a knickpoint to migrate quickly upstream and create a channel with a more favorable slope during a single flood. Based on Slingerland and Smith's (2004) model, we also propose that a low water-surface slope in the parent channel could be a direct driver for avulsions. In the Suncook River, this low water-surface slope was created in the backwater of a small mill dam in the parent channel. A 200-year flood that occurred in the Suncook River in 1936 did not create an avulsion. We suggest that ice floats could have damaged the dam and increased the water-surface slope of the parent channel, making an avulsion less favorable and reducing the depth of water flowing overbank. The topography in the path of the 2006 avulsion, which was lowered by activity in a sand pit starting in the 1960s, probably prevented water from finding a new path. We believe that these anthropogenic modifications directly contributed to the occurrence of the May 2006 avulsion in the Suncook River. These conditions are common throughout New England, and could increase the risk of avulsions in the region.
by Mariela C. Perignon.
S.B.
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Zhao, Beibei. "Identification of the cellular and molecular mechanisms governing the post-translational regulation of the neuron- specific potassium/chloride cotransporter KCC2." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=40680.
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The neuron-specific K+/Cl- cotransporter 2 (KCC2) is one of the major cation Cl- cotransporter (CCC) proteins in the central nervous system that controls Cl- homeostasis via mediating Cl- extrusion. KCC2 has been established as an essential protein in promoting the maturation of synaptic inhibition during development and controlling neuronal excitibility in the adult central nervous system (CNS). Although various mechanisms are known to regulate KCC2 gene expression, accumulating evidence has shown KCC2 activity can be altered on much shorter time scales in a manner of 10-20 minutes. This suggested post-translational mechanisms, which take place much more rapidly than gene expression, may also be an important means by which KCC2 function can be regulated. However, what these post-translational mechanisms are and how they contribute to the control of KCC2 function remain elusive. In this thesis, I set out to characterize the molecular mechanisms governing the post-translational regulation of KCC2, including its endocytosis, quaternary assembly, and cell surface expression. Specifically, my results suggest: 1) Endogenous KCC2 interacts with the clathrin-mediated endocytosis (CME) machinery; 2) KCC2 is constitutively endocytosed via a CME-dependent mechanism; 3) A di-leucine motif, 657LL658, is essential for both KCC2 constitutive endocytosis and the binding of KCC2 to the CME adaptor protein AP-2 complex; 4) Two regions within KCC2 proximal and central carboxyl terminus respectively mediate KCC2 dimerization, and in particular mutating the 657LL658 residues to alanines completely abolishes KCC2 dimerization; 5) The 657LL658 sequence is highly conserved amongst closely related K+/Cl- cotransporter proteins, but absent from the more distant Na+/Cl- cotransporters controlling Cl- uptake, suggesting an evolutionarily conserved mechanism may regulate the constitutive endocytosis and dimerization of functionally homologous KCC members; and 6) KCC2 expression at the neurLe co-transporteur d’ions K+ et Cl- (KCC2), spécifique aux neurones, est l’un des plus importants co-transporteurs de cations chlorure (CCC) du système nerveux central. Il contrôle l’homéostasie de la cellule en régulant l’extrusion d’ions chlorure. KCC2 est reconnu comme étant une protéine essentielle à la maturation de l’inhibition synaptique au cours du développement et au contrôle de l’excitabilité des neurones dans le système nerveux central de l’adulte. Bien que les mécanismes régulant l’expression de KCC2 soient connus, de nouvelles données suggèrent que l’activité de KCC2 peut aussi être modifiée sur de plus courtes périodes, de l’ordre de 10 à 20 minutes. Ceci suggère qu’un contrôle post-traductionnel, agissant beaucoup plus rapidement qu’un contrôle transcriptionnel, pourrait aussi être important dans la régulation de l’activité de KCC2. Toutefois, la nature de ces mécanismes post-traductionnels et la façon par laquelle ils contribuent à la fonction de KCC2 demeurent inconnus.Dans cette thèse, je vise à caractériser les mécanismes moléculaires qui gouvernent la régulation post-traductionnelle de KCC2, incluant son expression à la surface cellulaire, son endocytose et son assemblage quaternaire. Plus spécifiquement, mes résultats suggèrent que: 1) Le KCC2 endogène interagit avec la machinerie d’endocytose par clathrines (CME) ; 2) Le KCC2 est endocyté constitutivement par un mécanisme dépendant des clathrines; 3) Le motif di-leucine 657LL658 est essentiel non seulement à l’endocytose constitutive de KCC2, mais aussi à l’interaction entre KCC2 et le complexe protéique adaptateur AP-2; 4) Deux régions à l’intérieur de KCC2, l’une proximale et l’autre centrale à l’extrémité C-terminale, sont responsables de la dimérisation de KCC2 qui peut être abrogée par la substitution des leucine 657 et 658 par des alanines; 5) La séquence 657LL658 est très conservée par
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Bhagwandin, Candida B. "The Regulatory Mechanisms Governing The E3 Ubiquitin Ligase, Membrane-Associated RING-CH1 (MARCH1), And The Consequences Of Dysregulation On Metabolism." Diss., The University of Arizona, 2014. http://hdl.handle.net/10150/333037.
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Membrane-Associated RING-CH1 (MARCH1) is a highly-conserved E3 ubiquitin ligase identified as a potent regulator of the immune modulatory molecules, Major Histocompatibility Complex II (MHC-II), and co-stimulatory molecules (such as CD86). Antigen-presenting cells (APCs), such as dendritic cells, are induced to mature following interaction with stimuli, including microbial ligands and cytokines, whereupon MHC-II and CD86 surface expression is significantly upregulated. At the surface of the APC, these MARCH1 substrates provide signals critical for T cell activation and induction of the appropriate adaptive immune response. As a key regulator of the T cell-APC conversation, it is imperative to gain a thorough understanding of the underlying regulatory mechanisms governing MARCH1 expression and function, and the biological consequences of dysregulation of this E3 ligase. Indeed, it has been demonstrated that MARCH1 gene transcription is negatively-regulated upon APC maturation. We have shown that MARCH1 function is regulated at additional levels. We have observed that MARCH1 is rapidly degraded under normal circumstances. Further, its activity also appears to be negatively regulated by APC maturation, possibly through post-translational modifications including phosphorylation. The fact that MARCH1 is subject to multiple levels of regulation indicates a need for precise control of antigen-presentation. Interestingly, MARCH1-deficient mice on a normal diet show changes in organismal metabolism, which is known to be regulated, in part, by immune cells. We observed gender-associated dimorphisms in weight gain, visceral adipose tissue (VAT) deposits, and increased inflammation of the VAT, all characteristic of insulin-resistance and type II diabetes progression. However, despite exhibiting these hallmark risk factors of metabolic dysregulation, MARCH1-deficient mice show increased glucose tolerance compared to wildtype mice. Collectively, the data support the hypothesis that MARCH1 is stringently regulated to ensure proper control of the adaptive immune response, and suggest a novel role for this E3 ligase in the maintenance of metabolic homeostasis.
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Meini, Stefano [Verfasser]. "The Influence of Irreversible Electrochemical Reactions on the Fundamental Mechanisms Governing Capacity and Cycle Life of Li-O2 Batteries / Stefano Meini." München : Verlag Dr. Hut, 2013. http://d-nb.info/1042878412/34.
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Eraso, Pichot Abel. "Adaptive regulation of calcium excitability and energy metabolism by CREB-dependent transcription in astrocytes: study of the mechanisms governing astrocyte plasticity." Doctoral thesis, Universitat Autònoma de Barcelona, 2018. http://hdl.handle.net/10803/664170.
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Cada cop més evidencies suggereixen que els astròcits participen en les altes funcions cerebrals, controlant des de la transmissió sinàptica fins a les ones cerebrals globals i els processos d’aprenentatge i memòria. Diferents mecanismes han sigut proposats com a responsables d’aquests processos mediats per astròcits, entre ells, l’alliberació de gliotransmissors a partir de les senyals de calci així com la de lactat semblen els principals efectors. L’existència d’aquest control de les funcions cerebrals per part dels astròcits suggereix que aquestes cèl·lules poden regular les funcions cerebrals en resposta a experiència tan com les neurones, constituint el fenomen de plasticitat astrocitària. En neurones s’ha demostrat que el conegut factor de transcripció CREB, coordina les plasticitats sinàptica i intrínseca. El fet que, en astròcits, l’activació de CREB també està regulada per activitat cerebral, situa aquest factor de transcripció com a la diana ideal per promoure canvis dependents d’activitat en astròcits. En aquesta tesi hem analitzat l’efecte de l’activació de la transcripció depenent de CREB en astròcits, centrant-nos en l’excitabilitat del calci i en el metabolisme d’aquestes cèl·lules. Hem demostrat que l’activació de la transcripció depenent de CREB redueix les senyals citosòliques de calci a través del mitocondri a la vegada que augmenta l’alliberació de lactat, dos canvis que poden tenir impacte en la transmissió sinàptica. Una altra contribució important d’aquest estudi es l’anàlisi molecular dels mitocondris dels astròcits, que ha revelat que aquestes cèl·lules poden utilitzar metabòlits que no són glucosa, com ara àcids grassos, per respondre a les necessitats metabòliques energètiques. Els nostres resultats estableixen el CREB en astròcits con un eix de la plasticitat astrocitària i revelen la interacció entre la plasticitat i el metabolisme energètic en astròcits. Aquests descobriments constitueixen un avenç mecanístic i conceptual en el coneixement de la biologia dels astròcits i com aquestes cèl·lules poden controlar l’aprenentatge i la memòria.An increasing body of evidence suggests that astrocytes participate in higher-brain functions, controlling from synaptic transmission to global brain waves and learning and memory processes. Different mechanisms have been proposed to mediate these astrocyte-dependent processes, astrocytic lactate release and calcium-dependent gliotransmission being the main known effectors. The existence of control of brain functions by astrocytes suggests that astrocytes may shape brain functions in response to experience as much as neurons, thus constituting the phenomenon of astrocyte plasticity. In neurons, the transcription factor CREB is the best known coordinator of synaptic and intrinsic plasticity. The fact that, in astrocytes, CREB activation is also activity-dependent, positions CREB as an ideal target to promote plasticity-related changes in astrocytes, too. In this thesis, we have analyzed the effect of the activation of CREB-dependent transcription in astrocytes, specifically regarding calcium signals and metabolism. We have demonstrated that activation of CREB-dependent transcription reduces cytosolic calcium events via mitochondria and increases in lactate release, which may have impact on synaptic transmission. An important contribution of the study is the molecular analysis of astrocytic mitochondria, which has revealed that astrocytes may use fuels other than glucose such as fatty acids to meet basic energy metabolic demands. Taken together, our results establish astrocytic CREB as a hub in astrocyte-plasticity and shed light on the interplay between plasticity and energy metabolism in astrocytes; these findings constitute a conceptual and mechanistic advance in the knowledge of astrocytic biology and how these cells may control learning and memory.
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Moose, Holly Elizabeth. "Intrinsic Mechanisms Governing Retinal Progenitor Cell Biology: Retinal Homeobox Transcriptional Regulation and the Function of Forkhead Transcription Factors During Eye Development." The Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1251827616.
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Moroz, V. M., S. A. Moroz, and M. V. Moroz. "Analysis of the level of labor potential development in higher educational institutions of Ukraine: competitiveness of university graduates." Thesis, Henan science and technology press, 2016. http://repository.kpi.kharkov.ua/handle/KhPI-Press/46715.
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The article focuses on the possibility of using the criterion of competitiveness of domestic higher education institutions in the international labor market to analyze the level of development of labor potential of a particular university. In the article the relationship between the level of professional competence of future professionals and the quality of labor potential of universities which were involved in their formation and development. This article contains statistical information on the results of participation of Ukrainian university students in international student competitions, which the author used to characterize the quality of professional institutions in the field of competitiveness of future specialists. In addition, the article contains generalizations as for the possibility of usage the competitiveness feature level of graduates as an indicator (index) of the quality of university's labor potential.
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Andrade, Débora Machado [Verfasser], Stefan [Akademischer Betreuer] Hell, Jörg [Akademischer Betreuer] Enderlein, and Erwin [Akademischer Betreuer] Neher. "On the mechanisms governing plasma membrane organization - a STED-FCS investigation / Débora Machado Andrade. Gutachter: Jörg Enderlein ; Erwin Neher. Betreuer: Stefan Hell." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2014. http://d-nb.info/1051977304/34.
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Kurrer, Michael Odo. "Mechanisms governing initiation, progression and organ destruction in immunopathology : lessons from mouse models of autoimmune myocarditis, allergic asthma bronchiale and autoimmune diabetes /." Zürich, 2004. http://opac.nebis.ch/cgi-bin/showAbstract.pl?sys=000253371.
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Meini, Stefano [Verfasser], Hubert [Akademischer Betreuer] Gasteiger, Tom [Akademischer Betreuer] Nilges, and Kai-Olaf [Akademischer Betreuer] Hinrichsen. "The Influence of Irreversible Electrochemical Reactions on the Fundamental Mechanisms Governing Capacity and Cycle Life of Li-O2 Batteries / Stefano Meini. Gutachter: Hubert Gasteiger ; Tom Nilges ; Kai-Olaf Hinrichsen. Betreuer: Hubert Gasteiger." München : Universitätsbibliothek der TU München, 2013. http://d-nb.info/1038787106/34.
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Jensen, Lauren B. "Mechanism governing the cellular susceptibility to secretory phospholipase A2 /." Diss., CLICK HERE for online access, 2004. http://contentdm.lib.byu.edu/ETD/image/etd451.pdf.
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Jensen, Lauren Blackburn. "Mechanism Governing the Cellular Susceptibility to Secretory Phospholipase A2." BYU ScholarsArchive, 2004. https://scholarsarchive.byu.edu/etd/1137.
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Secretory phospholipase A2 (sPLA2) is an important part of apoptosis and disposal of damaged and dying cells. However, healthy cells are not susceptible to attack by sPLA2. Recent studies have focused on membrane properties necessary to induce susceptibility in both artificial and biological membranes. Hydrolysis of phospholipids by sPLA2 requires at least two preliminary steps: first, adsorption of the enzyme to the cellular membrane, and second, movement of a phospholipid into the active site of the enzyme. We determined the effects of susceptibility on each of the two steps and determined the contributions changing the equilibrium constants have on susceptibility. The equilibrium constant for step one increased by a factor of 2 during susceptibility, while the equilibrium constant for step two increased by a factor of 4. The rise in the second equilibrium constant caused the majority of the change in hydrolysis rate seen during susceptibility; the influence of the first equilibrium constant is minimal. We confirmed these results with adsorption studies (assessment of the first step). We additionally found that sPLA2 has a high affinity for the cellular membrane and that only a small percentage (3-5%) of the membrane is covered when all adsorption sites are filled by the enzyme. We proposed a mathematical model describing the mechanism of action of sPLA2, and we were able to experimentally justify the assumptions made in the model.
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Ho, Mei Yung. "Governing parameters for stress-dependent soil-water characteristics, conjunctive flow and slope stability /." View abstract or full-text, 2007. http://library.ust.hk/cgi/db/thesis.pl?CIVL%202007%20HO.
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Vezie, Deborah Lynn. "Ultrastructural studies of the mechanism governing compressive deformation in rigid-rod polymers." Thesis, Massachusetts Institute of Technology, 1993. http://hdl.handle.net/1721.1/12743.
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Lew, Yong Kyu. "Governing international technology alliances : innovation capabilities and performance outcomes in the mobile computing market." Thesis, University of Manchester, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.549054.
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This paper investigates governance mechanisms in international technology alliances (ITAs), firm-level innovation capabilities, and performance outcomes in the mobile computing market. This high-tech market is characterized by numerous cross-border strategic technology collaborations between hardware (HW) and software (SW) firms. Anchoring this work in the relational view, transaction cost economics, and the resource-based view, I develop a model and empirically test and validate relationships related to behavioral ITA governance mechanisms, innovation capabilities, and business performance. In the international cross-industry context, the findings explain to what extent complementary technology resources, through a relational governance mechanism, contribute to the innovation capabilities and superior business performance of high-tech firms, providing a competitive advantage. The data which is analyzed using partial least squares (PLS) path modeling, indicates technological commitment is a factor in expediting technology resource exchange in ITAs between HW and SW firms. The findings also show that the multi-dimensional business performance of firms is only influenced by market development capability, and not new product development capability in product innovation. The results are consistent, regardless of controlling for firm size, industry type, partner-specific experience, and alliance duration in the model. Thus, this research offers insights into how heterogeneous HW and SW high-tech firms in the emerging high-velocity market benefit from a relational governance mechanism in ITAs, thereby establishing competitive advantage through firm-level innovation capabilities. It also explains the relationships between firm-level product innovation mechanisms and business performance. Furthermore, this research provides evidence of the methodological usefulness of PLS path modeling in explaining new phenomena in international business, strategic management, and innovation fields.