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1
O'Malley, Claire E. "Structure and access : the role of structural factors in text comprehension and information." Thesis, University of Leeds, 1985. http://etheses.whiterose.ac.uk/322/.
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In this thesis it is argued that structural factors play an important role in facilitating the access, comprehension, and recall of textual information, especially when the content of the material is unfamiliar to the reader. A study was made of the effects of manipulating text structure, familiarity of subjects with the text type, familiarity with the content, and instructions given to subjects, on comprehending and recalling information from scientific research reports. The results show that subjects familiar with the text type are able to make use of structure as an encoding strategy, and that the use of this structural strategy improves comprehension and recall when the content is unfamiliar. The study suggests that teaching readers to make use of structure in processing text can facilitate comprehension and recall. These results provide support for previous theories concerning the role of text structure, most of which has focused on narratives, to the neglect of research on expository prose. It is argued that some of the problems involved in the research using narratives, in particular, the problem of the lack of distinction between structural factors and more general knowledge of the content, may be obviated by research with other text types, such as the one used in this study. It is also argued that users of computer-based documentation systems need similar kinds of structural cues for accessing online information as they do for offline text comprehension and retrieval, and that the efficacy and type of such structural cues depends on several factors, such as the task requirement, as well the level of experience of the user. A second study examined the patterns of use of an online documentation system, and showed that users need different forms of organisation of the information as 'access structures, depending on different task requirements. Finally, proposals are made for improving the design of online documentation systems and for conducting future research into the needs of users of such systems.
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Clark, D. J. "Histone H1 and its structural role in chromatin." Thesis, University of Cambridge, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.384413.
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Ding, Sharon. "Developing structural representations : their role in analogical reasoning." Thesis, University of Nottingham, 1995. http://eprints.nottingham.ac.uk/11896/.
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Recent research into the development of analogical reasoning has shown that young children are able to recognise and use relational similarity between situations, provided that they possess the necessary domain knowledge (Goswami, 1992). However, in most of the reported studies, the relational structure of the analogy has been made very salient. Circumstances where the relational structure of a problem has to be represented by the problem-solver themselves could result in differing performance. We do not know whether, or in what circumstances, children can correctly construct a representation of the relevant relational information. This thesis reports a series of experiments which investigate the role and development of structural representations for the purposes of analogical reasoning. The first two experiments tested whether primary aged children are able to construct an integrated external task representation by combining separate pieces of relational knowledge. Using series problems as a domain, they provided evidence that performance was not affected by the actual relation used, i.e. either spatial or non-spatial (abstract). However, it was observed that the order in which the task information was presented had an effect. The next four studies explored this by using spatial series problems. They showed that tasks which required a novel item to be placed to the left of (that is, at the front of) a partially ordered array inhibited performance. A further three experiments found that the reason for the inhibition was that unless the different pieces of relational information were highlighted as distinct items, they would be incorrectly integrated by using simple 'add-to-end' ordering rules. The final set of studies, using abstract evaluative relations in series problems, found that relational-highlighting effects generalised to these types of tasks. Also, the results showed that some evaluative relations were tied to either horizontal or vertical spatial representations and that performance was affected by how consistent the representation was with the child's experience of every-day life. The thesis showed that the ability to construct structural task representations is affected by features which are inherent in the presentation of specific tasks, and that incorrect structural representations in turn affect analogical mapping. These findings are discussed in terms of the 'generalised schemas' used during analogical mapping. It is suggested that these might be reconstructed using specific task information, rather than being retrieved intact from memory.
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Santosh, Vishaka. "Rep-DNA complexes and their role in AAV DNA transactions." VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5648.
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Adeno-associated Virus (AAV) Rep proteins are multifunctional proteins that carry out various DNA transactions required for the life cycle of AAV. The Rep proteins have been found to be important for genome replication, gene regulation, site-specific integration and play an essential role in genome packaging. There are two main groups of Rep proteins: large and small Reps; both groups are SF3 helicase family members. During DNA packaging, studies have shown that the small Rep proteins are critical to produce fully packed particles. Using stopped-flow kinetic analysis, we show a significant difference in helicase activity between the small and large Rep proteins that support the notion that the small Rep proteins are the primary motor to package DNA due to more efficient motor activity. That leaves the large Rep proteins to serve a different role during packaging. In previous studies, we have shown that the large Rep proteins have the ability to change their oligomeric state depending on the nature of the DNA substrate. We can observe double octameric rings with single-stranded DNA (ssDNA) and heptameric complex with double-stranded DNA (dsDNA). To understand Rep protein structural plasticity, we solved a 6.96 Å cryo-EM structure of Rep68*/ssDNA complex illustrating that the formation of Rep octamer rings is dominated by interactions between their N-terminal origin-binding domain (OBD) using the same interface utilized to recognize dsDNA specifically. Our analysis of the structural data suggests that the double octameric ring structure is stabilized by ssDNA that bridges octameric rings together. The structure shows that the helicase domains are highly flexible and that ssDNA is present at the center of the ring. In addition, we have solved a preliminary 12 Å model of Rep68*/dsDNA complex showing a heptameric ring encircling a DNA molecule. Our structural and functional data offer insights to the various Rep-DNA scaffolds that can perform diverse functions during the AAV life cycle.
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Barney, Emma Ruth. "The Structural Role of Lone PairIons in Novel Glasses." Thesis, University of Warwick, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.504773.
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The structures of several glass systems containing the lone pair ions lead or tellurium have been studied using a range of techniques including; neutron diffraction, magic angle spinning nuclear magnetic resonance (MAS NMR), Raman scattering, extended X-ray absorption fine structure (EXAFS) and density measurements. Comparisons with related crystals have also been used to elucidate the role lone pair ions play in glass structure. Studies of lead aluminate glasses (compositions from 64 to 80 mol.% PbO) and the related crystal phase, Pb9AIs0 21 (-69.2 mol.% PbO), using neutron diffraction have shown the crystal to be a good model for glasses with high PbO content. The AI-o peak in the total correlation functions, T(r), indicated that aluminium tetrahedra in the glasses are as well defined as those measured in the crystal. Furthermore, Pb9AIs021 has a coordination number of less than 3 in the region of2.0 - 2.5 A due to a proportion ofthe lead atoms occupying symmetric ionically bonded sites, with higher coordination numbers and longer bonds. Although samples with more than 72.5 mol.% PbO are 3-coordinated in the region, indicating all of the lead atoms are occupying asymmetric lead sites which have short PbO bonds, the coordination number decreases as the PbO content is reduced. There is a corresponding change in the densities of the samples and it is suggested that glasses with similar PbO content to Pb9AIs0 21 contain symmetric lead sites. In refining the crystal structure for Pb9AIs0 21 using neutron diffraction data it was found that the crystal could be formed over a range ofcompositions and a refinement ofthe occupancies gave a refmed composition ofPbs.49±O.Q7Als02o.43±O.13. Within error this composition is chargebalanced. The refined structure gave better agreement with the density ofthe crystal, the 27Al 'MAS NMR, and gave better thermal parameters for the 03 site, which is an unfavourable environment for oxygen atoms, being under-bonded and having a 1800 AI-0-AI bond angle. This site was found to have an occupancy of 0.76. . 10 and 20 mol.% Na20 sodium tellurite glasses were studied using neutron diffraction and, using data for potassium and lithium tellurites of equivalent composition, the bond length, coordination number and disorder ofthe first Na-o coordination shell were extracted. It was shown that the sodium environment ofthe 20 mol.% glass was equivalent to that ofthe stable crystal structure Na2Te409. However, a comparison of T(r) for the glass, the stable crystal and the meta-stable crystal demonstrated that the tellurium environment in the meta-stable crystalline phase ofNa2Te409 was a better model for the glass than the stable crystal. A range of tellurium borate glasses were made, and it was shown that the glasses phase separate, and the compositions measured did not agree with the compositions reported in the literature for glaSses with similar densities and fraction of four-coordinated boron (N4). Comparison ofT(r) measured using neutron diffraction with T(r) for alkali tellurites ofsimilar composition demonstrate that the tellurite network evolves differently with the addition of a network former, with enters the network, than with a modifier, which allows the formation of non-bridging oxygen atoms, reducing the Te-0 bond lengths and breaking up the network . In addition, tellurite network changes from 4- to 3-coordinated more quickly with the addition ofB20 3 than with the addition ofa modifier, and the Te - 0 peak in T(r) is more symmetric.
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Chambers, Adam C. "The role of ODV structural proteins in baculovirus replication." Thesis, Oxford Brookes University, 2012. https://radar.brookes.ac.uk/radar/items/b1027647-229d-acb7-0839-8aee864cc8f3/1/.
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Baculoviruses are arthropod-specific viruses with a circular, double-stranded DNA genome (80-180 kb). Two structural forms are produced during virus replication, comprising budded virus (BV) and occlusion-derived virus (ODV). The BV is produced from 12 hours post infection (hpi) and spreads the infection from tissue to tissue within the host. The ODV is formed 20 hpi and enveloped within occlusion bodies (OBs). The aim of this project was to elucidate the mechanisms involved in ODV production by deleting putative genes involved in ODV, but not BV production. A secondary aim of the project was to determine whether removing these genes improved the quantity/quality of recombinant proteins produced by baculovirus expression vectors.
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Takahashi, Mieko. "Gender dimensions in family life a comparative study of structural constraints and power in Sweden and Japan /." Doctoral thesis, Stockholm : Almqvist & Wiksell International, 2003. http://catalog.hathitrust.org/api/volumes/oclc/51722120.html.
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Horscroft, Nigel John. "Orbivirus non-structural protein NS2 : its role in virus replication." Thesis, University of Oxford, 1997. http://ora.ox.ac.uk/objects/uuid:9b550db6-dd9d-4127-941f-93eab2b6e038.
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Tremblay, André Y. "The role of structural forces in membrane transport: Cellulose membranes." Thesis, University of Ottawa (Canada), 1989. http://hdl.handle.net/10393/5886.
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The phenomena governing Transition RO/UF (nanofiltration) membrane transport have been critically studied. The residuals and predicted pore sizes of 965 individual permeation runs performed on 70 cellulose membranes were used to discriminate between several restricted transport models and various solute-solvent-membrane material interactions. Solute-membrane interactions were found to be mediated by the presence of structured solvent at the surface of the membrane. Two new interaction parameters, $\Psi\sb{DP}$ and $\kappa\sp\prime$ describing structural solvent forces at the surface of a membrane have been quantified. For solvent mediated interactions, the potential energy of a solute molecule $\phi\sbsp{DP}{\prime}(\underline d$) at a distance $\underline d$ from the membrane surface can be obtained by combining $\Psi\sb{DP}$ and $\kappa\sp\prime$ and the Stokes-Einstein radius a$\sb{s}$ of the solute as follows:$$\phi\sbsp{DP}{\prime}(\underline d) = -\Psi\sb{DP}\ a\sb{s}\ e\sp{-\kappa\sp\prime(\underline{d}-a\sb{s})}$$ A method to evaluate $\Psi\sb{DP}$ from simple permeation experiments and $\kappa\sp\prime$ from direct force measurements is given. This approach permits the decoupling of solute size and solute-membrane material interactions in predicting separation. The inverse of $\kappa\sp\prime$ was found to be approximately equal to the diameter of a solvent molecule. A linear correlation was obtained between the square root of $\Psi\sb{DP}$ and the solubility parameter $\delta\sb{SP}$ for all solutes tested in this work. The slope of this correlation reflects the ability of the membrane material to structure water dipoles at a solid-liquid interface. The ordinate's intercept of this correlation was equal to the solubility parameter of the solvent which implies that steric solute interactions $(\Psi\sb{DP}\to 0)$ occur when $\delta\sb{SP}$ of the solute approaches that of the solvent. The results of this study indicate that a solute molecule can penetrate hydrated layers of solvent at the surface of a material to different extents depending on its size and solvent compatibility. These findings are assumed to be applicable to reverse osmosis transport and indicate that if a membrane material is to be used in RO it must be capable of structuring solvent molecules at its surface. Several parametric studies were performed using the surface force pore flow (SFPF) model to determine the exact shape of the velocity profile in the membrane pore under conditions of solute adsorption and rejection. These studies were performed at various feed concentrations and values of $\lambda$ for polyethylene glycol, of molecular weight 1000, and casein. The shape of the solute separation vs. solute radius curve was studied parametrically as a function of pressure for four restricted transport models. The shape of this curve was also determined, using a radially dependent pore model (RDPM), for adsorptive and repulsive van der Waals interactions, electrical double layer (DLVO) interactions, increased viscosity in the membrane pore and effects of chain permeability and the shape of the interacting surface. Morphological reasons are given for the general inability to reduce the pore radius of cellulose membranes below 1.5 nm. Viscometric measurements performed on cellulose casting solutions indicate that the dissolved elements of the solution exist as rigid, rod-like structures. It is proposed, that the pore size of cellulose membranes be limited by the regular occurrence of indentations on the protofibril surface and by stacking limitations, enhanced by the geometry of the protofibrils. This interpretation is conform with the folded ribbon model of a cellulose protofibril described in the literature.
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Shaw, Andrew Edward. "The Role of Non-Structural Proteins in Bluetongue Virus Replication." Thesis, University College London (University of London), 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.519459.
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Brown, L. E. "Dissecting the structural role of GABAA receptors in synapse formation." Thesis, University College London (University of London), 2016. http://discovery.ucl.ac.uk/1476757/.
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GABAergic synapse formation involves the establishment of specific cellcell contacts between the presynaptic GABAergic neurones and their postsynaptic targets. Postsynaptic GABAA receptors (GABAARs) themselves have been shown to play a direct structural role in the initiation of functional synapses (Fuchs et al., 2013). Yet, characterisation of the molecular mechanisms underlying their structural involvement remains sparse. As the large N-terminal extracellular domains (ECDs) of the GABAAR subunits reside within the synaptic cleft, we hypothesised that these domains participate in trans-synaptic interactions with cleft-spanning presynaptic proteins. To investigate our hypothesis, a baculovirus/Sf9 cell expression system was used to express and purify the ECDs of the α1, β2 and γ2 GABAAR subunits. These ECDs were utilised in proteomics and mass spectrometry experiments to identify candidate trans-synaptic interacting proteins. To dissect the structural role(s) played by individual GABAAR subunits in synapse formation, a co-culture model system incorporating GABAergic medium spiny neurones and HEK293 cells expressing different combinations of GABAARs was developed. The results indicated that the γ2 subunit was necessary for contact formation and that its 'synaptogenic' effects were influenced by the subtype of α and β GABAAR subunits that were incorporated within the receptor. To elucidate whether the synaptogenic effects of the GABAAR subunits were directly mediated by their ECDs, the purified α1, β2 and γ2 ECDs were added to HEK293-MSN co-cultures at 14 Day in vitro (DIV). Contact formation was reduced in the presence of each of the exogenous ECDs. In parallel, the ECDs were added to pure cultures of MSNs to analyse their structural effects on GABAAR cluster size and number. The results demonstrated that synapsespecific effects were observed for each ECD. In summary, the synaptogenic effects of GABAARs depend on their individual subunit composition, with the ECDs structurally contributing towards the initial cell-cell contacts.
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Tao, Alice. "Form-maker and collaborator : the role of the structural engineer." Thesis, Massachusetts Institute of Technology, 2009. http://hdl.handle.net/1721.1/53067.
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Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Civil and Environmental Engineering, 2009.<br>Includes bibliographical references (p. 49).<br>Over the past century, there have existed two major types of structural engineers. Some, like Robert Maillart, contributed greatly to the advancement of new forms. Others, such as Peter Rice, produced their most innovative work in collaboration with architects. The present study analyzes the work and methodology of both groups of engineers, with the purpose of defining the common ground between them. Finally, there is a detailed discussion of the 'form-makers' and 'collaborators' in the context of the present day, in an effort to describe the basis for quality in structural engineering.<br>by Alice Tao.<br>M.Eng.
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Venkateswaran, Anuradha. "Role of cracks in creep of brittle, polycrystalline, structural ceramics." Diss., Virginia Polytechnic Institute and State University, 1985. http://hdl.handle.net/10919/49951.
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An analytical study was conducted of the effect of cracks on creep of polycrystalline, brittle structural ceramics. Two independent mechanisms of contribution of cracks were defined. The mechanism of elastic creep by crack growth represents the rate of increase in strain, with time, resulting from the time-dependent decrease in elastic moduli of the material, due ·to crack growth. The mechanism of crack-enhanced creep provides a measure of the increase in creep rate over that in an identical but crack-free material, due to the local stress field associated with the cracks and the resultant transfer of stress to the adjacent, crack-free material. Creep rates due to these mechanisms were quantified for simple crack geometries. It was shown that the contribution of cracks can result in an idealized 4-stage creep curve for a brittle, polycrystalline ceramic, in contrast to the conventional 3-stage creep curve for metals. The four stages consist of a primary or crack incubation period, a secondary sigmoidal region resulting from growth of microcracks along grain boundary facets, a tertiary or crack-enhanced stage associated with arrested microcracks, and a quarternary stage comprising crack linkage and coalescence. It was demonstrated that the formation and growth of cracks during creep can result in apparent power-law creep, positive grain size dependence of the creep rate, and grain size-dependent creep activation energy. It can also account for observations of decreasing creep rate with increasing time in constant load creep tests, anomalous stress relaxation behavior in structural ceramics, significantly higher creep rates in tension tests than in compression tests, and discrepancy between diffusion coefficients inferred from creep studies and measured in diffusivity experiments.
A simple model was presented for the effect of cracks on creep rate in bending, based on the time-rate of change of curvature of a bend specimen.
Analysis of the effect of cracks on creep was extended to a general state of multiaxial stress, through matrix formulation of stress, creep rate, and creep compliance tensors. Derivation of components of the creep compliance tensor from analogs in elasticity was demonstrated for crack-enhanced creep, for uniaxial and uniform triaxial tension, for simple crack geometries. It was demonstrated that materials containing cracks can exhibit a finite rate of creep under hydrostatic tension, in contrast to a corresponding creep rate of zero in crack-free materials.
Recommendations are made for analysis and interpretation of experimental creep data for structural ceramics.<br>Ph. D.<br>incomplete_metadata
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Lansdon, Lisa Ann. "The role of structural variation in cleft lip and palate." Diss., University of Iowa, 2018. https://ir.uiowa.edu/etd/6172.
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Clefts of the lip and/or palate (CL/P) are one of the most common birth defects in the world occurring about every 1 in 700 live births. Individuals with non-syndromic clefting (NSCL/P) account for about 70% of all cleft cases and exhibit a cleft only whereas syndromic occurrences (SCL/P) include additional cognitive or structural abnormalities. Linkage, genome-wide association, candidate gene, animal model, sequencing and copy number variant (CNV) analyses have been used to study CL/P and have established that it is a heterogeneous, complex disorder. However, the impact of identified sequence variants on protein structure and the contribution of structural genetic variation to CL/P remains poorly understood.
In our first analysis we reassessed the phenotype of a 30-year-old individual of SCL/P and noticed phenotypic overlap with Hartsfield syndrome, a rare syndrome resulting from sequence variants in Fibroblast growth factor 1 (FGFR1). We sequenced the coding region of FGFR1 and identified a novel, de novo variant. Due to the fact sequence variants in FGFR1 contribute to multiple syndromes encompassing a wide phenotypic spectrum, we performed an extensive literature search to record every published sequence variant of FGFR1 and mapped it to the protein structure by disease and phenotype. Although no statistically significant protein domain-phenotype correlations were identified, many regions neared significance. This work stresses the need for systematic, comprehensive phenotyping of patients and provides a method for assessing the impact of the location of sequence variants within the 3D structure of the protein.
Although rare and common CNVs have been identified in individuals with CL/P, prior to our work no large-scale studies of rare CNVs for the identification of novel clefting genes had been performed. For our second set of analyses, we conducted two such studies, first focusing on a smaller cohort of 140 individuals with NSCL/P from the Philippines to establish our informatic and functional validation pipeline. We used whole-genome tiling arrays to assess rare deletions overlapping genes not previously implicated in clefting, and identified one deletion overlapping Isthmin1 (ISM1) and a deletion just 3’ of the gene in a second affected individual. Functional validation of Ism1 in Xenopus laevis showed strong expression in structures necessary for craniofacial development, and morpholino and CRISPR/Cas9 knockdown of Ism1 resulted in a median cleft lip in some embryos, establishing ISM1 as a novel craniofacial patterning gene. We then expanded our study and assessed genomic CNVs in 1021 individuals with NSCL/P and 81 individuals with SCL/P, finding no differences in CNV number, load or burden between these groups. We also identified 8 putative clefting genes overlapped by deletions in two or more individuals but at a rare (< 1% frequency) in the cohort. Functional validation of these genes using CRISPR/Cas9 in zebrafish and Xenopus tropicalis is currently underway.
This work has identified a novel sequence variant leading to the diagnosis of Hartsfield syndrome in an individual with SCL/P, developed an innovative method for assessing the impact of sequence variation on protein structure, improved our understanding of the contribution of CNVs to SCL/P and NSCL/P and identified several putative novel clefting loci which may help explain a portion of the missing heritability of CL/P.
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Patra, Gurudatt. "Structure of mitotic chromosome and the role of condensin protein in the structural organization of chromosomes." Electronic Thesis or Diss., Strasbourg, 2024. http://www.theses.fr/2024STRAJ020.
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Au cours de la mitose, la chromatine interphasique subit une compaction massive en structures en forme de bâtonnets. Les condensines sont des complexes protéiques dont on sait qu'ils jouent un rôle majeur dans l'organisation des chromosomes mitotiques. Les eucaryotes possèdent deux complexes de condensines conservés, à savoir les condensines 1 et 2. Des études in vitro sur des modèles d'ADN nus montrent que les condensines ont une activité d'extrusion de boucles dans l'organisation des chromosomes. Cependant, il reste encore beaucoup à explorer en ce qui concerne l'étude de la fonction des condensines dans l'environnement encombré de la chromatine. Nous avons utilisé la technologie halo tag où le domaine SMC2 des condensines est marqué par fluorescence à l'aide d'un ligand halo TMR. Cette approche nous aide à localiser les régions riches en condensines dans les chromosomes mitotiques partiellement décondensés en utilisant la cryo-microscopie en lumière à l'intérieur des chromosomes vitrifiés pour les études de cryo-tomographie électronique. Nos tomographies montrent les complexes de condensine dans l'environnement chromatinien. Cela ouvre une fenêtre sur l'étude de l'activité de liaison à l'ADN de la condensine, l'oligomérisation ou le regroupement de la condensine et son interaction avec d'autres composants non histoniques des chromosomes mitotiques<br>During mitosis, the interphase chromatin undergoes a massive round of compaction into rod-shaped structures. Condensins are protein complexes that have been known to play a major role in mitotic chromosome organization. Eukaryotes have two conserved condensin complexes, namely condensin 1 and 2. In vitro studies on naked DNA templates show evidence for loop extrusion activity of condensins in chromosome organization. However, there is still a lot to explore regarding the study of condensin function inside the crowded chromatin environment. We have used halo tag technology where the SMC2 domain of condensins is tagged to fluorescently label using a halo TMR ligand. This approach helps us to locate condensin-rich regions in partially decondensed mitotic chromosomes using cryo-light microscopy inside the vitrified chromosomes for cryo-electron tomography studies. Our tomograms show condensin complexes inside the chromatin environment. This opens up a window into the study of DNA binding activity of condensin, the oligomerization or clustering of condensin and its interaction with other non-histone components of mitotic chromosomes
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Zufferli, Alessandra. "Role of sphingolipids in muscle atrophy." Phd thesis, INSA de Lyon, 2011. http://tel.archives-ouvertes.fr/tel-00701490.
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The sphingolipids are a family of membrane lipids with only a structural role, influencing lipid bilayer properties, but they also act as effector molecules with essential roles in many aspects of cell biology. The sphingolipids ceramide, sphingosine and S1P have shown opposite effects: whereas ceramide and sphingosine usually inhibit proliferation and promote apoptotic responses to different stress stimuli, S1P is known to stimulate cell growth, and promote cell survival. Ceramide can be produced through the de novo synthesis pathway, and by membrane sphingomyelin hydrolysis catalyzed by sphingomyelinases. Both pathways can be activated by the pro-inflammatory cytokine TNFa. Because this cytokine has been shown to promote muscle loss and seems to be crucial in the development of cachexia, we hypothesized that the formation of ceramide, or a metabolite, can be involved in tumor-induced muscle wasting. We investigated the role of ceramide in the in vitro atrophic effects of TNFa on differentiated C2C12 myotubes, by using cell permeant ceramides and inhibitors of sphingolipid metabolism. We observed that TNFa atrophic effects, as evaluated by the reduction in myotube area, are mimicked by exogenous ceramides, supporting the idea that ceramide can participate in muscle atrophy. To verify if ceramide is a mediator of TNFa-induced atrophy, and to identify the metabolites potentially involved, we analyzed the effects of drugs able to block sphingolipid metabolism at different steps: the inhibition of de novo synthesis pathway was unable to restore myotube size in the presence of TNFa whereas the inhibitors of neutral sphingomyelinases reversed TNFa-induced atrophy. Moreover, an accumulation of ceramide and sphingosine induced pro-atrophic effects, whereas sphingosine-1-phosphate had a protective effect. These observations establish that in C2C12 myotubes, ceramide or other downstream metabolites such as sphingosine, produced by the neutral sphingomyelinase pathway in response to TNFa stimulation, participate in cell atrophy. To evaluate the in vivo role of sphingolipids, we treated BalbC mice carrying C26 adenocarcinoma woth Myriocin, an inhibitor of the de novo pathway of ceramide synthesis, that is able to deplete muscle tissue in all sphingolipids, was administered daily to the animals. This treatment partially protected animals against tumor-induced loss of body weight and muscle weight, without affecting the size of tumors. Moreover, myriocin treatment significantly reversed the decrease in myofiber size associated with tumor development, and reduced the expression of atrogenes Foxo3 and Atrogin-1, showing that it was able to protect against muscle atrophy. These results strongly suggest that ceramide, or a downstream sphingolipid metabolite, is involved in tumor-induced muscle atrophy. The sphingolipid pathway thus appears as a new potential target of pharmacological interventions aiming at protecting muscle tissue against atrophy.
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Burgess, Richard James. "Structural change in the music industry : the evolving role of the musician." Thesis, University of South Wales, 2010. https://pure.southwales.ac.uk/en/studentthesis/structural-change-in-the-music-industry(9bc91707-aa31-4037-a303-0b0116b7d163).html.
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The recording industry is little more than one hundred years old. In its short history there have been many changes that have redefined roles, enabled fortunes to be built and caused some to be dissipated. Recording and delivery formats have gone through fundamental conceptual developments and each technological transformation has generated both positive and negative effects. Over the past fifteen years technology has triggered yet another large-scale and protracted revision of the business model, and this adjustment has been exacerbated by two serious economic downturns. This dissertation references the author’s career to provide context and corroboration for the arguments herein. It synthesizes salient constants from more than forty years’ empirical evidence, addresses industry rhetoric and offers methodologies for musicians with examples, analyses, and codifications of relevant elements of the business. The economic asymmetry of the system that exploits musicians’ work can now be rebalanced. Ironically, the technologies that triggered the industry downturn now provide creative entities with mechanisms for redress. This is a propitious time for ontologically reexamining music business realities to determine what is axiological as opposed to simply historical axiom. The primary objective herein is to contribute to the understanding of applied fundamentals, the rules of engagement that enable aspirants and professionals alike to survive and thrive in this dynamic and capricious vocation. The secondary goal is to empower creative practitioners to circumvent systemic injustices that have been perpetrated and perpetuated by the oligopolistic market conditions that have prevailed for most of the century of recorded sound.
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De, Melo Abinadabe Jackson. "Molecular basis for the structural role of human DNA ligase IV." Thesis, Aix-Marseille, 2016. http://www.theses.fr/2016AIXM4040.
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Les défauts dans la réparation des cassures double-brin de l'ADN (DSBs) peuvent avoir d'importantes conséquences pouvant entrainer une instabilité génomique et conduire à la mort cellulaire ou au développement de cancers. Dans la plupart des cellules mammifères, le mécanisme de Jonction des Extrémités Non Homologues (NHEJ) est le principal mécanisme de réparation des DSBs. L'ADN Ligase IV (LigIV) est une protéine unique dans sa capacité à promouvoir la NHEJ classique. Elle s'associe avec deux autres protéines structuralement similaires, XRCC4 et XLF (ou Cernunnos). LigIV interagit directement avec XRCC4 pour former un complexe stable, tandis que l'interaction entre XLF et ce complexe est médiée par XRCC4. XLF stimule fortement l'activité de ligation du complexe LigIV/XRCC4 par un mécanisme encore indéterminé. Récemment, un rôle structurel non catalytique a été attribué à LigIV (Cottarel et al., 2013). Dans le travail de thèse présenté ici, nous avons reconstitué l'étape de ligation de la NHEJ en utilisant des protéines recombinantes produites dans des bactéries afin d’une part, d'explorer les bases moléculaires du rôle structural de LigIV, d’autre part de comprendre le mécanisme par lequel XLF stimule le complexe de ligation, et enfin de mieux comprendre comment ces trois protéines coopèrent au cours de la NHEJ. Nos analyses biochimiques suggèrent que XLF via son interaction avec XRCC4 lié à LigIV, pourrait induire un changement conformationnel dans la LigIV. Ce réarrangement de la ligase exposerait son interface de liaison à l'ADN ce qui lui permettrait alors de ponter deux molécules indépendantes d'ADN, une capacité indépendante de l'activité catalytique de LigIV<br>Failure to repair DNA double-strand breaks (DSBs) may have deleterious consequences inducing genomic instability and even cell death. In most mammalian cells, Non-Homologous End Joining (NHEJ) is a prominent DSB repair pathway. DNA ligase IV (LigIV) is unique in its ability to promote classical NHEJ. It associates with two structurally related proteins called XRCC4 and XLF (aka Cernunnos). LigIV directly interacts with XRCC4 forming a stable complex while the XLF interaction with this complex is mediated by XRCC4. XLF strongly stimulates the ligation activity of the LigIV/XRCC4 complex by an unknown mechanism. Recently, a structural noncatalytic role of LigIV has been uncovered (Cottarel et al., 2013). Here, we have reconstituted the end joining ligation step using recombinant proteins produced in bacteria to explore not only the molecular basis for the structural role of LigIV, but also to understand the mechanism by which XLF stimulates the ligation complex, and how these three proteins work together during NHEJ. Our biochemical analysis suggests that XLF, through interactions with LigIV/XRCC4 complex, could induce a conformational change in LigIV. Rearrangement of the LigIV would expose its DNA binding interface that is able to bridge two independent DNA molecules. This bridging ability is fully independent of LigIV’s catalytic activity. We have mutated this interface in order to attempt to disrupt the newly identified DNA bridging ability. In vitro analysis of this LigIV mutant will be presented as well as a preliminary in vivo analysis
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Fielder, Anne. "A structural role for the H-NS protein in bacterial chromatin." Thesis, University of Oxford, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.308709.
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Patterson, Clare. "The role of structural and discourse-level cues during pronoun resolution." Phd thesis, Universität Potsdam, 2013. http://opus.kobv.de/ubp/volltexte/2014/7128/.
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Pronoun resolution normally takes place without conscious effort or awareness, yet the processes behind it are far from straightforward. A large number of cues and constraints have previously been recognised as playing a role in the identification and integration of potential antecedents, yet there is considerable debate over how these operate within the resolution process. The aim of this thesis is to investigate how the parser handles multiple antecedents in order to understand more about how certain information sources play a role during pronoun resolution. I consider how both structural information and information provided by the prior discourse is used during online processing. This is investigated through several eye tracking during reading experiments that are complemented by a number of offline questionnaire experiments.
I begin by considering how condition B of the Binding Theory (Chomsky 1981; 1986) has been captured in pronoun processing models; some researchers have claimed that processing is faithful to syntactic constraints from the beginning of the search (e.g. Nicol and Swinney 1989), while others have claimed that potential antecedents which are ruled out on structural grounds nonetheless affect processing, because the parser must also pay attention to a potential antecedent’s features (e.g. Badecker and Straub 2002). My experimental findings demonstrate that the parser is sensitive to the subtle changes in syntactic configuration which either allow or disallow pronoun reference to a local antecedent, and indicate that the parser is normally faithful to condition B at all stages of processing. Secondly, I test the Primitives of Binding hypothesis proposed by Koornneef (2008) based on work by Reuland (2001), which is a modular approach to pronoun resolution in which variable binding (a semantic relationship between pronoun and antecedent) takes place before coreference. I demonstrate that a variable-binding (VB) antecedent is not systematically considered earlier than a coreference (CR) antecedent online. I then go on to explore whether these findings could be attributed to the linear order of the antecedents, and uncover a robust recency preference both online and offline. I consider what role the factor of recency plays in pronoun resolution and how it can be reconciled with the first-mention advantage (Gernsbacher and Hargreaves 1988; Arnold 2001; Arnold et al., 2007). Finally, I investigate how aspects of the prior discourse affect pronoun resolution. Prior discourse status clearly had an effect on pronoun resolution, but an antecedent’s appearance in the previous context was not always facilitative; I propose that this is due to the number of topic switches that a reader must make, leading to a lack of discourse coherence which has a detrimental effect on pronoun resolution.
The sensitivity of the parser to structural cues does not entail that cue types can be easily separated into distinct sequential stages, and I therefore propose that the parser is structurally sensitive but not modular. Aspects of pronoun resolution can be captured within a parallel constraints model of pronoun resolution, however, such a model should be sensitive to the activation of potential antecedents based on discourse factors, and structural cues should be strongly weighted.<br>Pronomenauflösung erfolgt normalerweise scheinbar mühelos und ohne bewusste Anstrengung. Jedoch ist die Verarbeitung von pronominalen Referenzen aus linguistischer Sicht ein hochkomplexer Prozess. Durch unterschiedliche wissenschaftliche Studien wurden bereits zahlreiche Faktoren ermittelt, die bei der Pronomenauflösung eine Rolle spielen, allerdings herrscht weitgehend noch keine Einigkeit darüber, wie genau diese Faktoren die Verarbeitung von Pronomen beeinflussen. Ziel dieser Dissertation ist es zu untersuchen, wie der Leser/Hörer mit Pronomen umgeht, denen mehrere Antezedenten zugeordnet werden können, um zu verstehen, welche Rolle bestimmte Informationsquellen in der Verarbeitung von Pronomen spielen. Besondere Beachtung findet dabei, wie strukturelle Eigenschaften sowie Informationen aus dem vorangegangenen Diskurs für die Suche nach einem passenden Antezedenten benutzt werden. Die angewandte Untersuchungsmethode der vorliegenden Dissertation ist Eye-tracking during reading, ergänzt mit verschiedenen offline-Fragebögen.
Die Experimente erforschen die Rolle der folgenden Aspekte in der Verarbeitung von Pronomen: Prinzip B der Bindungstheorie (Chomsky 1981; 1986), Koreferenz und Variablenbindung laut der Primitives of Binding Hypothese (Reuland 2001, Koornneef 2008), Antezedentenreihenfolge im Satz, und Diskursstatus des Antezedents. Obwohl es zeigt sich, dass der Hörer/Leser sensibel für subtile Veränderungen in der syntaktischen Konfiguration ist, wie z.B. für die Reihenfolge der Antezedenten im Satz und für den Diskursstatus des Antezedenten, gibt es keinen Nachweis dafür, dass Variablenbindung zeitlich vor Koreferenz erfolgt. Einige Aspekte der Auflösung pronominaler Referenzen können in einem parallel constraints model erfasst werden, allerdings sollte so ein Modell strukturelle Informationen stark gewichten und sensitiv sein für die Aktivierung potenzieller Antezedenten aufgrund von Diskursfaktoren.
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Rowlands, Ruth. "The role of structural disorder in crystalline, glassy and liquid materials." Thesis, University of Bath, 2016. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.687387.
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Schachtner, Hannah. "Investigation of the functional and structural role of podosomes in megakaryocytes." Thesis, University of Glasgow, 2013. http://theses.gla.ac.uk/4032/.
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Megakaryocytes (Mks) give rise to platelets via extension of proplatelet arms, which are released through the vascular sinusoids into the bloodstream. Mks and their precursors undergo varying interactions with the extracellular environment in the bone marrow during their maturation and positioning in the vascular niche. The dynamic remodeling of the actin cytoskeleton and the formation of cell -matrix contacts such as podosomes are fundamental for this process. However, the role and function of podosome structures in Mks are poorly understood. Podsomes are well characterized in different cell-types of the myeloid lineage such as macrophages and dendritic cells. Their formation is associated with a dynamic F-actin turnover, fascilitated cell migration and the degradation of extracellular matrix (ECM). The function of podosome organelles is multifaceted and is described in association with cell adhesion, motility, ECM lysis, invasion and mechanosensors. A fundamental analysis of podosomes was necessary to define a potential function for these structures in Mks. I determined an abundant formation of classical podosomes with an F-actin core and a Vinculin ring in primary murine Mks, which were adherent on different physiological relevant ECM substrates such as fibrinogen, collagen I and a native basement membrane. Lifetime analysis was performed and was demonstrated to be dependent on the substrate as well as on Myosin-II activity. Another key feature of podosomes, the degradation of ECM proteins, could be detected and was mediated in an MMP associated manner. Furthermore, I verified that podosomes are necessary to penetrate a native basement membrane, which is amongst others part of blood vessels. II In this thesis I therefore demonstrate multifaceted properties of Mk podosomes and direct a potential function of these structures in the process of Mk maturation and possibly in platelet formation
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Brahmachari, Ruchi. "The role of the insula in dyslexia : a structural MRI approach /." Available to subscribers only, 2008. http://proquest.umi.com/pqdweb?did=1594499201&sid=14&Fmt=2&clientId=1509&RQT=309&VName=PQD.
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Griswold, Ian James. "The structural role of CheW in the bacterial chemotaxis receptor complex /." view abstract or download file of text, 2001. http://wwwlib.umi.com/cr/uoregon/fullcit?p3018365.
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Thesis (Ph. D.)--University of Oregon, 2001.<br>Typescript. Includes vita and abstract. Includes bibliographical references (leaves 163-175). Also available for download via the World Wide Web; free to University of Oregon users.
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Chapman, Brandon D. "The role of disorder in structural phase transitions in perovskite ferroelectrics /." Thesis, Connect to this title online; UW restricted, 2003. http://hdl.handle.net/1773/9692.
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Lusher, Dean Stewart. "Masculinities in local contexts : structural, individual and cultural interdependencies /." Connect to thesis, 2006. http://eprints.unimelb.edu.au/archive/0002448.
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Scott, Drew Austin. "RECOVERY OF WHOLE SOIL CONDITIONS THROUGH RESTORATION FROM AGRICULTURE AND ITS ROLE IN MEDIATING PLANT-PLANT COMPETITION." OpenSIUC, 2015. https://opensiuc.lib.siu.edu/theses/1826.
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The tallgrass prairie has been severely reduced in size, making restoration important to maintain communities and functions of this ecosystem. A chronosequence approach was used to determine recovery of physical and biological soil properties. The recovery models of soil properties provided information to explain the variation in total C stock of the whole soil. Recovery models also provided information to design a competition experiment based on variation in whole soil conditions with land use history. The filter framework hypothesis is a useful concept for examining tallgrass prairie restoration; the theory states only a subset of species in the region will be able to establish in a specific location due to abiotic and biotic filters. With this theory in mind, I explored the influence of whole soil conditions as affected by land use history (cultivation/restoration) and how these conditions altered plant-plant competition dynamics of a dominant grass was studied. Belowground plant biomass recovers with cessation of tillage and restoration back to prairie, providing an organic matter source for microbial populations to recover and soil macroaggregates to form. This has potential to increase C sequestration in soils and decrease nitrous oxide efflux from soils. Intact 5.5 cm dia cores were collected to a depth of 10 cm in each field to determine physical and biological soil properties. Belowground plant, microbial community, and soil structure properties were modeled to recover coinciding with an increase in total C stock of the whole soil. Structural equation modeling revealed that soil structure physically protecting organic matter explained the most variation in soil carbon sequestration with restoration. Most of the total C was contained within the macroaggregate size fraction; within this fraction most of that C is within the microaggregates within macroaggregates fraction. Soil structure is critical for recovery of soil carbon stocks and the microaggregate within macroaggregate fraction is the best diagnostic of sequestered C. ANCOVA results indicate that while the slopes of nitrous oxide efflux rates did not differ, cumulative efflux differed, though this was not related to time since restoration. Dominant grasses, such as Andropogon gerardii, can exclude subordinate species from grassland restorations. Thus, understanding changes in competition dynamics of dominant grasses could help maintain richness in grassland restorations. There may be changes in competition dynamics with whole soil conditions affected by land use history (cultivation/restoration) as plant available nutrients will decrease, microbial populations will increase, and soil structure will improve with restoration from cultivation to prairie. Using 4 soil treatments of varying land use history with four species treatments, to determine if effects are general or species specific, pairwise substitution competition experiments were conducted. Relative A. gerardii response to competition was compared among soil and species treatments using competition intensity and competition importance indices utilizing final plant biomass, relative growth rate based on maximum height, and net absolute tiller appearance rate. The experiment was conducted over 18 weeks, allowing A. gerardii to flower. A significant intensity result and significant importance results utilizing biomass measurements indicated that the 16 year restored prairie soil cause A. gerardii to be a relatively better competitor against forbs than in all other soils except for cultivated soil, likely due to positive plant-soil feedbacks. Significant importance results utilizing tiller appearance rate indicated that the cultivated and 3 year restored prairie soil caused A. gerardii to be a relatively better competitor than in the 16 year restored and never cultivated native prairie soils, likely due to changes in whole soil conditions related to land use history. There were only general soil effects, as soil treatments did not interact with species treatments. A. gerardii was a relatively better competitor against non-leguminous forbs, indicating that legumes are a better competitor for a limiting nutrient than A. gerardii or that this species is not in direct competition with legumes.
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Goode, Natassia. "Determinants of the control of dynamic systems: The role of structural knowledge." Thesis, The University of Sydney, 2011. http://hdl.handle.net/2123/8967.
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In educational and organisational settings it has become common practice to use computer-based complex problems that represent dynamic systems for assessment and training purposes. In the interpretation of performance scores and the design of training programs, it is often assumed that the capacity to effectively control the outcomes of a dynamic system depends on the acquisition of structural knowledge. Control performance scores are generally interpreted as evidence of individual differences in the capacity to acquire and utilise structural knowledge and training programs typically try to improve learners‘ mental models of the system of interest. However, a causal relationship between the acquisition of structural knowledge and successful system control has not been established, and some findings suggest that it may be possible to control dynamic systems in the absence of structural knowledge. Therefore, the goals of this project were to determine the conditions that are required to learn how to control dynamic systems and the psychological processes that separate successful from less successful problem solvers in the performance of this task. The main emphasis of this investigation was to clarify the role of structural knowledge in the control of dynamic systems and to identify sources of individual differences in problem solvers‘ capacity to acquire such knowledge and apply it in a goal-orientated application. In a series of studies, a combined experimental and differential approach was adopted to address these goals. This consisted of the experimental manipulation of the task and structural characteristics of complex problems combined with the use of process indicators and external psychometric tests. Study 1 examined whether problem solvers need to directly interact with a dynamic system in order to acquire structural knowledge that is useful for system control. Study 2 examined whether increments in structural knowledge lead to improvements in control performance and whether dynamic systems can be successfully controlled without structural knowledge. Study 3 examined whether the relationship between structural knowledge and control performance is moderated by system complexity. Each of these studies also investigated the role of fluid intelligence in the acquisition and application of knowledge. Additional methodological contributions include the application of Cognitive Load Theory to the design of the instructions used to manipulate structural knowledge, the use of randomly generated control performance scores to evaluate the success of performance and the development of a theoretically driven operationalisation of system complexity. Across the studies, it was found that structural knowledge was a necessary condition of better than random performance and that there was a causal relationship between structural knowledge and control performance. However, the likelihood that structural knowledge would be acquired and utilised was found to be dependent on the complexity of the system. Small increments in system complexity resulted in floor effects on performance. Fluid intelligence was found to play a crucial role in the acquisition and subsequent application of knowledge. Overall, the results indicate that the complexity of the system determines the amount of knowledge that is acquired by the problem solver, which in turn, combined with their intelligence, determines the quality of their control performance.
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St-Amour, J. C. "The structural role of titanium in alkali and alkaline-earth bearing glasses." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp04/mq29254.pdf.
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Rundqvist, Louise. "Thermodynamical and structural properties of proteins and their role in food allergy." Doctoral thesis, Umeå universitet, Institutionen för medicinsk kemi och biofysik, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-68020.
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Proteins are important building blocks of all living organisms. They are composed of a defined sequence of different amino acids, and fold into a specific three-dimensional, ordered structure. The three-dimensional structure largely determines the function of the protein, but protein function always requires motion. Small movements within the protein structure govern the functional properties, and this thesis aims to better understand these discrete protein movements. The motions within the protein structure are governed by thermodynamics, which therefore is useful to predict protein interactions. Nuclear magnetic resonance (NMR) is a powerful tool to study proteins at atomic resolution. Therefore, NMR is the primary method used within this thesis, along with other biophysical techniques such as Fluorescence spectroscopy, Circular Dichroism spectroscopy and in silico modeling. In paper I, NMR in combination with molecular engineering is used to show that the folding of the catalytical subdomains of the enzyme Adenylate kinase does not affect the core of the protein, and thus takes a first step to linking folding, thermodynamic stability and catalysis. In paper II, the structure of the primary allergen from Brazil nut, Ber e 1, is presented along with biophysical measurements that help explain the allergenic potential of the protein. Paper III describes the need for a specific Brazil nut lipid fraction needed to induce an allergenic response. NMR and fluorescence spectroscopy is used to show that there is a direct interaction between Ber e 1 and one or several components in the lipid fraction.
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Tai, Hung, and 戴雄. "The role of the non-structural protein, NS1, in influenza virus replication." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B44660303.
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Magadmi, Rania. "Structural and functional role of CADM1 on mast cell-neuron cross-talk." Thesis, University of Sheffield, 2016. http://etheses.whiterose.ac.uk/15889/.
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Preacher, Kristopher J. "The Role of Model Complexity in the Evaluation of Structural Equation Models." The Ohio State University, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=osu1054130634.
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PELOSI, Orietta. "The structural role of light elements in magmas: P, Cl and S." Doctoral thesis, Università degli Studi di Camerino, 2008. http://hdl.handle.net/11581/401883.
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This study is focused on the geochemical and structural behaviour of light elements in magmas. In particular we are interested in investigating the role of phosphorus, chlorine and sulfur in silicate glasses in order to get important information to apply in a natural model. The geochemical and structural role of P, S and Cl in silicate glasses of composition relevant for the Earth Sciences has been investigated by X-ray Absorption Spectroscopy (XAS). The geochemical behavior of these elements in silicate melts and glasses is of major importance for problems ranging from volcano-climate interactions to the genesis of ore deposits of great economic importance to industrial glass-forming processes and treatment of vitreous waste material from refuse incineration activities. Evaluation of such problems requires new data on the structural environments around P, Cl and S dissolved in silicate melts and potential interactions with metal cations. Direct structural data (local bonding environment) are lacking, due to experimental difficulty in analyzing minor to trace light elements. We collected high quality XANES and EXAFS data on synthetic glasses in order to obtain information on the local chemical and structural environment around the studied elements. Use of synthetic glasses produced under controlled pressure, temperature and oxygen fugacity conditions allowed to understand how the structural and geochemical role of these light elements vary according to the physical and chemical conditions existing in the magma chamber. Data analysis has been accomplished by comparison with well characterized model compounds with known absorber oxidation state and coordination number. Theoretical XANES calculations have further helped in understanding the chemical and structural environment of the studied elements (e.g. cations bonded to [PO4]3- groups or to Cl- and S2- anions) in the synthetic glasses
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Kazan, Ramy. "Role of aIF5B in archaeal translation initiation." Thesis, Institut polytechnique de Paris, 2022. http://www.theses.fr/2022IPPAX043.
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Dans les trois domaines du vivant, le démarrage de la traduction permet la sélection précise du codon de démarrage sur un ARN messager, spécifiant ainsi la phase de lecture pour la synthèse protéique. Cette étape essentielle implique un complexe de démarrage macromoléculaire (IC, environ 1 million de Daltons) comprenant la petite sous-unité du ribosome, l’ARNm, l’ARNt initiateur méthionylé spécifique et des facteurs de démarrage (IFs). Une fois le codon de démarrage sélectionné au site P du ribosome et la grande sous-unité ribosomale associée, les facteurs de démarrage sont relâchés. Le ribosome est alors prêt pour l'étape d'allongement. Chez les archées et les eucaryotes, malgré des étapes initiales très différentes pour la liaison de l'ARNm à la petite sous-unité du ribosome, les mécanismes d'identification des codons de démarrage présentes d’importantes similitudes.Après la sélection du bon codon, les étapes tardives du démarrage eucaryotes et archées mettent en œuvre deux facteurs, a/eIF1A et a/eIF5B. Ces deux facteurs sont aussi des orthologues des protéines IF1 et IF2. Ainsi les étapes tardives du démarrage ont un caractère universel.Nous avons déterminé la structure par cryo-microscopie électronique d'un complexe de démarrage de la traduction archée contenant une petite sous-unité ribosomale, un ARNm modèle, un ARNt initiateur méthionylé et les deux facteurs de démarrage aIF5B et aIF1A. Les deux facteurs sont très bien définis dans la densité électronique. Le facteur aIF5B est lié à la méthionine de l'ARNt initiateur par son domaine IV et il est en contact avec le corps de la petite sous-unité ribosomal près de la région uS12-h5 par ses domaines I, II et III. De plus, et pour la première fois, une interaction entre aIF5B et aIF1A est observée. Cette structure nous permet de modéliser les étapes tardives du démarrage et de comprendre comment aIF5B facilite l'association de la grande sous-unité ribosomale. Nos résultats sont comparés aux mécanismes eucaryotes et bactériens<br>Translation initiation universally occurs with accurate selection of the start codon that defines the reading frame on the mRNA. The mechanism involves a macromolecular complex composed of the small ribosomal subunit, the mRNA, a specialized methionylated initiator tRNA and initiation factors (IFs). Once the start codon is selected at the P site on the small ribosomal subunit and the large subunit is associated, the IFs are released and an elongation competent ribosome is formed. Although the general principles are the same in the three domains of life, the molecular mechanisms are different in bacteria, eukaryotes and archaea as illustrated by the different number and types of the initiation factors.In eukaryotes and in archaea, late steps of translation initiation involve the two initiation factors a/eIF1A and a/eIF5B. Importantly, a/eIF5B and a/eIF1A are orthologues of the bacterial proteins IF1 and IF2 respectively. Therefore, late steps of translation initiation have a universal character.We determined the cryo-EM structure of an archaeal translation initiation complex containing the small ribosomal subunit, a model mRNA, the methionylated initiator tRNA and the two initiation factors aIF5B and aIF1A. The two initiation factors are very well defined in the cryo-EM map. aIF5B is bound to the methionine group of the initiator tRNA by its domain IV while domains I, II, and III contacts the body part of the small ribosomal subunit in the uS12, h5 region. For the first time, interaction between archaeal aIF1A and aIF5B is observed. The structure allows us to model the late steps of translation initiation and to understand how aIF5B facilitates the joining of the large ribosomal subunit. Our results are compared to the eukaryotic and bacterial cases
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Smith, Paul. "Exploring the role of technology acceptance in business buying of tax technology." Thesis, University of Manchester, 2014. https://www.research.manchester.ac.uk/portal/en/theses/exploring-the-role-of-technology-acceptance-in-business-buying-of-tax-technology(7dd62167-266f-4372-bf8a-c189fb235fd6).html.
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This study developed and empirically examined a model to help understand how key individuals in businesses decide on whether or not to buy and utilise technology in the context of managing their obligations in relation to business taxes. In restricting the frame of reference to a taxation context, it enabled a link to be made to individual decision making, as it is ordinarily the case that one lead buyer is evident in the context of tax and technology in organisations. The model was developed from a review of extant literature in the areas of technology acceptance, behavioural intention, and consumer and business buying models. The overall model was built on a framework that has at its core the Augmented Technology Acceptance Model (Taylor & Todd, 1995a). A correspondence between attitude to use of the technology and product quality is theorised, allowing a connection to a wider model of purchase intention. The initial model was developed with thirteen hypotheses, ultimately leading to an examination of intention to buy tax technology. After an initial pilot study, in the main study a questionnaire was designed to capture empirical data for measurements related to the model. Data collected from 125 informants (i.e. senior tax staff in large organisations) about tax technology buying decisions they were currently considering was used to empirically test the model, using Structural Equation Modelling. The low sample size caused a need to simplify the original model to retain statistical power. This had the result of reducing the number of hypotheses to ten. The analysis was performed testing the measurement model and the model fit and thereby investigating its underlying hypotheses. The results supported the key hypotheses and the overall explanatory power of the model in examining intention to buy tax technology was strong. The use of technology acceptance principles as core to helping explain buying intention for tax technology was strongly supported. Only one hypothesis was not supported, relating to a proposed positive relationship between Relationship Quality and Intention to Buy constructs. Potential explanations for this finding with regard to relationship quality were introduced. The general research contributions and implications of the study were also discussed.
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Brown, Hillary E. "Crustal rupture, creation, and subduction in the Gulf of California, Mexico and the role of gas hydrate in the submarine Storegga slide, offshore Norway." Laramie, Wyo. : University of Wyoming, 2007. http://proquest.umi.com/pqdweb?did=1475164361&sid=10&Fmt=2&clientId=18949&RQT=309&VName=PQD.
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Seegar, Tom CM. "TIED TOGETHER: A MOLECULAR ROLE FOR TIE1 IN ANGIOPOIETIN TIE2 SIGNALING." VCU Scholars Compass, 2010. http://scholarscompass.vcu.edu/etd/2122.
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The primary function of the vascular system is the maintenance of oxygen homeostasis for all metazoan tissue. Angiogenesis, the remodeling and maintenance of new blood vessels from an existing vessel, is primarily controlled through the endothelial specific receptor tyrosine kinase Tie2, and the orphan receptor tyrosine kinase, Tie1. Although these receptors share highly conserved, genetic and biochemical analysis has shown these receptors have distinct and essential roles in angiogenesis. Tie2 activation typically results in vessel stability and quiescences and has further been shown to interact with all four sub-types of the angiopoietin signaling factors, Ang1-4. Conversely, Tie1 is involved in vascular remodeling and has no known ligands. The aim of this study is to resolve the molecular mechanism in which Tie1 modulates Angiopoietin-induced Tie2 signaling. Using biophysical, structural, and biochemical assays we show Tie1 directly interacts with Tie2 via electrostatic interactions housed within the extracellular domains. The binding of Tie1 to Tie2 attenuates Tie2 phosphorylation. We further show the constitutive agonist of Tie2, Ang-1, is capable of excluding Tie1 initiating Tie2 activation. Whereas the antagonist, Ang-2, is in incapable of excluding Tie1. Finally, we identify a region within the angiopoietin receptor-binding domain that is capable of including or excluding Tie1 from Tie2. Based upon the available data, we provide a model for Angiopoietin-induced Tie2 signaling.
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zhang, qifang. "Role of Jak/Stat pathway in the pathogenesis of breast cancer." VCU Scholars Compass, 2010. http://scholarscompass.vcu.edu/etd/41.
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The Jak/Stat signaling cascade mediates cell proliferation, differentiation, survival, apoptosis and immune responses. Aberrant activation of this pathway mediates neoplastic transformation and abnormal growth of many malignancies including breast cancer, the most common cancer among women, and the second leading cause of cancer deaths in women in United States. The mechanism by which the Jak/Stat pathway modulates the pathogenesis of breast cancer is unclear. This dissertation elucidates roles of Jak/Stat members that mediate the pathogenesis of breast cancer. For these studies, we used 4T1 mouse mammary tumor cells as a model which mimics human breast cancer. First, we investigated the role of Tyk2 tyrosine kinase in the pathogenesis of breast cancer. Here we show for the first time that compared with wild type mice, Tyk2 -/- mice show increased tumor growth rate as well as metastatic disease and splenomegaly when inoculated with 4T1 breast cancer cells. Such increased tumorigenicity was associated with a significant decrease of IFNg production in 4T1 tumor-bearing Tyk2 deficient mice T cells compared with wild type (WT) mice. We demonstrated that NK cells or CD8+ T cells control tumor growth in both Tyk2-/- and WT mice, but neither Tyk2-/- NK cells alone nor Tyk2-/- CD8+ T cells alone do not contribute to enhanced tumor growth and metastatic disease of Tyk2-/- mice. Tumor-bearing Tyk2-/- mice have increased level of myeloid-derived suppression cells than tumor-bearing mice. Tyk2-/- MDSCs have a slight increase in suppression of T cell proliferation. Since elevated phosphorylation of Stat3 has been seen in human and murine breast cancer, and expression of Stat3 in the mitochondria (mitoStat3) appears to have important affects on cell growth, we studied the ability of Stat3 targeted to the mitochondria (MLS Stat3) to influence growth and metastasis of 4T1 cells. We show that a serine mutant of Stat3 expressed in the mitochondria (Stat3 S727A) inhibits the ability of 4T1 tumor cells to grow and metastasize. In contrast, a serine to aspartic acid mutant of Stat3 (S727D) enhances tumorigenesis. We found that expression of mitochondrial-targeted Stat3 does not affect cell growth rate in cell culture under normal conditions, however in low glucose, the serine to alanine mutant shows reduced growth rate and ability to invade. Moreover, we found that expression of mitochondrial-targeted Stat3 protects cells from hypoxia. Our data indicate that serine phosphorylation of mitochondrial-localized Stat3 is required for cell transformation. In summary, our studies provided new insights into the role of Stat3 in breast cancer and suggest new therapeutic targets for the treatment of this disease.
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Zhu, Yanlei. "The structural and functional role of whirlin in inner ear hair cells during development." Electronic Thesis or Diss., Sorbonne université, 2020. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2020SORUS358.pdf.
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Le syndrome d'Usher est l'un des syndromes neurosensoriels génétiques les plus courants, affectant à la fois la vision et l'audition. A ce jour, neuf gènes portant des mutations sont liés à ce syndrome. Mon projet de thèse porte sur la protéine Usher appelée Whirline, une protéine à domaine PDZ cruciale dans les systèmes auditifs et visuels. Nous avons caractérisé la fonction du troisième domaine PDZ, exposé à l'extrémité C-terminale de la protéine. Le PDZ3 reconnaît au moins sept protéines portant des motifs PBM (PDZ Binding Motif): CASK, MPP1, Myosine 15a, Protocadhérine 15 CD3, Cadhérine 23, Harmonine a1 et Taperine. Nous avons résolu les structures à haute résolution de quatre d'entre elles et mis en évidence la capacité de liaison très variée du PDZ3 de la Whirline à divers partenaires des cellules ciliées cochléaires. Du côté N-terminal de la Whirline, le premier domaine PDZ1 reconnait à la fois des motifs peptidiques et des lipides. Nous avons caractérisé en détail ce PDZ1, isolé et inclus dans des constructions multi-domaines, en interaction avec des protéines et des membranes lipidiques par diverses approches biophysiques. La structure de PDZ1 en complexe avec des PBM partenaires et avec des lipides a été résolu, mettant en évidence les résidus impliqués dans de telles interactions. De plus, nous avons documenté le rôle du domaine HHD1 situé juste en amont du domaine PDZ1 et impliqué dans l'auto-association de la Whirline. L’ensemble de ces propriétés de la Whirline est lié à sa fonction de protéine d'échafaudage qui assure l'ancrage des protéines membranaires Usher, un réseau de protéines sous-membranaires essentielles au développement des cellules ciliées<br>Usher syndrome is one of the most common genetic neurosensory syndromes, which affects both vision and hearing. So far, nine genes’ mutations have been found related to the Usher syndrome. My PhD project focuses on one Usher protein Whirlin, a PDZ containing multi-domain scaffolding protein. We characterised the function of the third PDZ domain which is fully exposed at the C-terminus of the protein. PDZ3 recognizes at least seven proteins PBM (PDZ Binding Motif): CASK, MPP1, Myosin 15a, Protocadherin 15 CD3, Cadherin 23, Harmonin a1 and Taperin, and we solved the high-resolution structures of four of them. We highlighted the unexpected binding capacity of the Whirlin PDZ3. The first N-terminal PDZ1 is a domain of dual functions, which recognizes both protein PBM and lipids. We deeply characterised the PDZ1 in interaction with proteins and lipid membranes by various biophysical approaches. We solved the structures of PDZ1 in complex with partner PBM and with lipid, and highlighted the residues specifically involved in such interactions. In addition, we emphasized the role of the upstream N-terminal HHD1 domain adjacent to the PDZ1 domain and involved in the self-association of Whirlin. Altogether, these properties of Whirlin are related to its function as a scaffolding protein that ensures the anchoring of the membrane Usher proteins, a submembrane protein network essential for the development of hair bundle and for the photoreceptor functioning
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HOLLAND, MICAH. "RETHINKING THE ROLE OF FOREIGN INVESTMENT AND INTERNATIONAL LENDERS IN DEVELOPING ECONOMIES." University of Cincinnati / OhioLINK, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1163699231.
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Francy, Christopher Alfred. "Investigating the Functional Role of Drp1 in Mitochondrial Fission." Case Western Reserve University School of Graduate Studies / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case1480952643685349.
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King, Oscar, and Vinyoh Yiyen. "The Role of Structural Bonds in the Development of Strategic Buyer-Supplier Relationships." Thesis, Internationella Handelshögskolan, Högskolan i Jönköping, IHH, Centre of Logistics and Supply Chain Management, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:hj:diva-18389.
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Background: The need to cut costs, save money, become profitable, be innovative, improve product quality and be responsive to customers’ demands is encouraging some organizations to form strategic relationships with suppliers. In achieving this, certain joint investments, called structural bonds, are developed within the relationship life-cycle. Although the bonds tend to tie down the partners and also create impediments for the termination of the relationship, they inevitably contribute to the achievement of mutual goals and sustaining competitive advantage. Past researches failed to relate the structural bonds’ development to any of the stages of the relationship life-cycle, which this study investigated. Purpose: The purpose of this research is to investigate why and in which stages of a strategic buyer-supplier relationship are structural bonds initiated. Method: A multiple case study approach, involving four companies, was undertaken to achieve the purpose of this study. The method used in collecting the empirical data is in-depth interviews with purchasing employees of these companies: Lagermetall AB, Atlas Copco AB, SAAB Tech AB and Husqvarna AB. Results: Most of the structural bonds, based on this study, were introduced at the beginning of the relationships. Some of the reasons for introducing these bonds are: improved product quality, joint product development, knowledge transfer, innovation and communication. Though the bonds may be introduced by the more powerful organization in the relationship, there is interdependency in the relationship. The bonds influenced the following in the relationship: trust, commitment and cooperation, information sharing, and performance but also generated lock-in effects.
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Chakrabarty, Arnab. "Role of sensory input in structural plasticity of dendrites in adult neuronal networks." Diss., lmu, 2013. http://nbn-resolving.de/urn:nbn:de:bvb:19-155241.
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陳炳賢 and Ping-yin Jason Chan. "The role of avoidance in anxiety and depression: a structural equation modeling study." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B41547585.
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Caunt, Christopher James. "The role of Ras subfamily GTPases in structural regulation of IL-1 signalling." Thesis, University of Sheffield, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.251408.
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Tsim, Matthew Chung Wah. "Structural and biochemical studies of FtsZ and its role in bacterial cell division." Thesis, University of Cambridge, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.709454.
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Chan, Ping-yin Jason. "The role of avoidance in anxiety and depression a structural equation modeling study /." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B41547585.
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Son, Tiffany G. "The Role of a Conserved Helix in the Structural Evolution of Cro Protein." Thesis, The University of Arizona, 2011. http://hdl.handle.net/10150/144968.
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PASQUALINI, LORETTA. "Models of innovation in small firms: the role of structural and behavioural variables." Doctoral thesis, Università Politecnica delle Marche, 2011. http://hdl.handle.net/11566/242005.
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L’obiettivo di questa tesi è studiare i modelli di innovazione delle imprese, in particolare delle piccole e medie imprese (PMI) che operano nel contest economico italiano. I modelli di innovazione sono studiati in base a due filoni principali: da un lato l’analisi delle variabili strutturali, ad esempio l’appartenenza ad un settore produttivo o ambiti tecnologici, che determinano il comportamento innovativo delle imprese. Dall’altro lato, il
focus è sulle variabili comportamentali delle imprese che influenzano il modo di fare
innovazione delle stesse. L’analisi della variabili strutturali come determinanti dell’innovazione, parte dallo studio
della tassonomia di Pavitt e dalla sua validità per le imprese manifatturiere italiane. Studi precedenti hanno mostrato che la tassonomia di Pavitt non sembra completamente efficace nel descrivere i processi di innovazione delle imprese manifatturiere italiane. Alcuni
problemi metodologici, circa la significatività degli indicatori quantitativi misurati e la natura dei dati di riferimento, hanno riguardato queste ricerche. Di conseguenza, in questo lavoro, sono stati costruiti indicatori quantitativi per descrivere le indicazioni qualitative di Pavitt con l’obiettivo di renderli più idonei a testare la tassonomia di Pavitt. Inoltre, indicatori quantitativi sono stati applicati su dati appartenenti
a un database più appropriato (CIS) che descrive in maniera più accurata i modelli di
innovazione delle imprese italiane. I risultati mostrano una migliore corrispondenza del comportamento innovativo delle imprese alle indicazioni di Pavitt rispetto ai risultati dei lavori precedenti. Comunque, sembra evidenziarsi una dicotomia tra science based e specialized suppliers da un lato e supplier dominated e scale intensive dall’altro, riguardo il
modo di fare innovazione. Le variabili comportamentali sono state studiate grazie all’approfondimento dei concetti di
definizione e misura mento del grado di innovazione che è stato utilizzato come misura dell’risultato dell’innovazione. L’analisi è basata sull’ipotesi che entrambi opportunità tecnologiche e opportunità non tecnologiche influenzano il grado di innovazione. Il focus è su come le collaborazione per innovare che le imprese stabiliscono con soggetti esterni
possano influenzare il grado delle innovazioni introdotte. L’obiettivo è dimostrare che le collaborazioni delle imprese con i soggetti esterni non appartenenti al settore produttivo
dell’impresa e più specializzati nell’attività di ricerca, come le università e gli istituti di ricerca pubblici, siano più efficaci per ottenere innovazioni con un alto grado di novità. Lo studio delle determinanti del grado di innovazione in generale potrebbe essere utile per
meglio indirizzare le iniziative politiche volte a sostenere l’attività di innovazione nelle imprese manifatturiere italiane.<br>The aim of thesis is study models of innovation of firms, especially of small and medium enterprises (SMEs) which act on Italian economic context. Models of innovation are studied by basing on two mains fields: on the one hand the
analysis of structural variables, for example affiliation to an industry or technological aspects, that determine innovative behavior of firms. On the other hand, the focus is on firms’ behavioral variables that influence way to do innovation of firms. The analysis of structural variables as determinants of innovation, it starts from study of
Pavitt’s taxonomy and of its validity for Italian manufacturing firms. Previous studies
showed that Pavitt’s taxonomy seems not completely effective in order to describe
innovation processes of Italian manufacturing firms. Some methodological problems, about the significance of quantitative indicators measured and the nature of referring data find on
previous analyses, were encountered on this research. Therefore quantitative indicators are built in order to describe qualitative predictions of Pavitt aiming to render them more suitable in order to test Pavitt’ taxonomy. In addition, quantitative indicators are measured on data of an appropriate database (Community
Innovation Survey by ISTAT) that describes accurately innovation models of Italian firms. Results highlight existence of a dichotomy about way of doing innovation between two clusters: science based and specialized supplier on the one hand and supplier dominated and scale intensive on the other hand. Behavioral variables are studied thanks to deepening into definition and measurement of degree of innovation that it is used as measure of innovation output. Analysis is based on the hypothesis that both technological opportunities and non technological opportunities influence the degree of innovation. The focus is on how collaborations to innovate, that firms establish with external subjects, could influence the degree of introduced innovations.
The aim is demonstrate that influence of non industrial subjects specialized in research
activity, as universities or public research institutes, is more effective to obtain innovations with an high degree of novelty respect to influence of subjects belonging to firm’s industry, as supplier or clients or competitors. Results from model applied to whole manufacturing
industry confirm hypothesis of major influence on degree of innovation of non industrial subjects. Application of model on Pavitt’s group register particular results different among groups which press to move analysis from Pavitt’s groups to single industry in order of better identify firms innovative behavior.