Dissertations / Theses on the topic 'Tangles'
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Caples, Christine. "Classifying 2-string tangles within families and tangle tabulation." Diss., University of Iowa, 2017. https://ir.uiowa.edu/etd/5918.
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A knot can be thought of as a knotted piece of string with the ends glued together. A tangle is formed by intersecting a knot with a 3-dimensional ball. The portion of the knot in the interior of the ball along with the fixed intersection points on the surface of the ball form the tangle. Tangles can be used to model protein- DNA binding, so another way to think of a tangle is in terms of segments of DNA (the strings) bounded by the protein complex (the 3-dimensional ball). In this thesis, we look at an algorithm used to list tangles. We also classify tangles into families.
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Jones, Garrett L. "Modeling knotted proteins with tangles." Diss., University of Iowa, 2013. https://ir.uiowa.edu/etd/4862.
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Proteins play a vital role in all organic life. The structure of a protein is directly related to its function. Hence, how they fold and what they fold into is of great interest. Given the spontaneous manner in which many proteins fold, one would not expect complicated structures like knots to occur in native states. Nevertheless, current research has shown that proteins do indeed contain local knots; some with as many as 6 crossings. In general, the role of knots in proteins and how they are formed is not completely understood. This thesis develops models of protein knotting by using knot theory and tangles. Mathematically, a knot is just a topological embedding of a circle in Euclidean 3-space, R3, or the unit 3-sphere, S3. A tangle is defined as a pair, (B, T), where B is a 3-dimensional ball and T is a set of disjoint arcs properly embedded in B. We begin with 2-string tangles and use the tangle calculus developed by Ernst and Sumners to set up tangle equations. In this model the strings of the 2-tangles represent the protein chain. Solutions to these 2-string tangle equations are then found. Motivated by the hypothesized folding pathway of the knotted protein DehI, a more complicated 3-string tangle model is developed. It is hypothesized that a terminal end of the protein is threaded through two loops. In the proposed model, the threading of a terminal end of the protein through two loops is translated into a Γ;-move on 3-string tangles. A Γ;-move is a special type of 3-string tangle replacement. The 3-braids are utilized as a subset of 3-string tangles to find solutions in a limited case. Additionally, tangle models give insight into how to make specific knot types in proteins. We finish with a general result by proving that any knot of unknotting number 2 can be unknotted by the Γ;-move. With these models we determine which knots are the most biologically possible to occur in proteins.
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Kennedy, Kathleen Grace. "A Diagrammatic Multivariate Alexander Invariant of Tangles." Thesis, University of California, Santa Barbara, 2013. http://pqdtopen.proquest.com/#viewpdf?dispub=3596170.
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Recently, Bigelow defined a diagrammatic method for calculating the Alexander polynomial of a knot or link by resolving crossings in a planar algebra. In this dissertation, I will present my multivariate version of Bigelow's algorithm for the Alexander polynomial. The advantage to my algorithm is that it generalizes easily to a multivariate tangle invariant. I will also present preliminary results on the connection to Jana Archibald's tangle invariant and conclude with ideas for future research.
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Street, Ethan J. "Towards an Instanton Floer Homology for Tangles." Thesis, Harvard University, 2012. http://dissertations.umi.com/gsas.harvard:10193.
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In this thesis we investigate the problem of defining an extension of sutured instanton Floer homology to give an instanton invariant for a tangle. We do this in three separate steps. First, we investigate the representation variety of singular flat connections on a punctured Riemann surface \(\Sigma\). Suppose \(\Sigma\) has genus \(g\) and that there are \(n\) punctures. We give formulae for the Betti numbers of the space \(\mathcal{R}_{g,n}\) of flat \(SU(2)\)-connections on \(\Sigma\) with trace 0 holonomy around the punctures. By using a natural extension of the Atiyah-Bott generators for the cohomology ring \(H^*(\mathcal{R}_{g,n})\), we are able to write down a presentation for this ring in the case \(g=0\) of a punctured sphere. This is accomplished by studying the intersections of Poincaré dual submanifolds for the new generators and reducing the calculation to a linear algebra problem involving the symplectic volumes of the representation variety. We then study the related problem of computing the instanton Floer homology for a product link in a product 3-manifold \((Y_g, K_n) := (S^1 \times \Sigma, S^1 \times \{n pts\})\).<\p> It is easy to see that the Floer homology of this pair, as a vector space, is essentially the same as the cohomology of \(\mathcal{R}_{g,n}\), and so we set ourselves to determining a presentation for the natural algebra structure on it in the case \(g = 0\). By leveraging a stable parabolic bundles calculation for \(n = 3\) and an easier version of this Floer homology, \(I _*(Y_0, K_n, u)\), we are able to write down a complete presentation for the Floer homology \(I _*(Y_0, K_n)\) as a ring. We recapitulate somewhat the techniques in \([\boldsymbol{27}]\) in order to do this. Crucially, we deduce that the eigenspace for the top eigenvalue for a natural operator \(\mu^{ orb} (\Sigma)\) on \(I_* (Y_0, K_n)\) is 1-dimensional.Finally, we leverage this 1-dimensional eigenspace to define an instanton tangle invariant THI and several variants by mimicking the de nition of sutured Floer homology SHI in \([\boldsymbol{22}]\). We then prove this invariant enjoys nice properties with respect to concatenation, and prove a nontriviality result which shows that it detects the product tangle in certain cases.
Mathematics
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Zibrowius, C. B. "On a Heegaard Floer theory for tangles." Thesis, University of Cambridge, 2017. https://www.repository.cam.ac.uk/handle/1810/263367.
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The purpose of this thesis is to define a “local” version of Ozsváth and Szabó’s Heegaard Floer homology HFL^ for links in the 3-sphere, i.e. a Heegaard Floer homology HFT^ for tangles in the 3-ball. The decategorification of HFL^ is the classical Alexander polynomial for links; likewise, the decategorification of HFT^ gives a local version ∇ˢ of the Alexander polynomial. In the first chapter of this thesis, we give a purely combinatorial definition of this polynomial invariant ∇ˢ via Kauffman states and Alexander codes and investigate some of its properties. As an application, we show that the multivariate Alexander polynomial is mutation invariant. In the second chapter, we define HFT^ in two slightly different, but equivalent ways: One is via Juhász’s sutured Floer homology, the other by imitating the construction of HFL^. We then state a glueing theorem in terms of Zarev’s bordered sutured Floer homology, which endows HFT^ with additional structure. As an application, we show that any two links related by mutation about a (2,−3)-pretzel tangle have the same δ-graded link Floer homology. This result relies on a computer calculation. In the third and last chapter, we specialise to 4-ended tangles. In this case, we give a reformulation of HFT^ with a glueing structure in terms of (what we call) peculiar modules. Together with a glueing theorem, we can easily recover oriented and unoriented skein relations for HFL^. Our peculiar modules also enjoy some symmetry relations, which support a conjecture about δ-graded mutation invariance of HFL^. However, stronger symmetries would be needed to actually prove this conjecture. Finally, we explore the relationship between peculiar modules and twisted complexes in the wrapped Fukaya category of the 4-punctured sphere. There are four appendices, some of which might be of independent interest: In the first appendix, we describe a general construction of dg categories which unifies all algebraic structures used in this thesis, in particular type A and type D modules from bordered theory. In the second appendix, we prove a generalised version of Kauffman’s clock theorem, which plays a major role for our decategorified invariants. The last two appendices are manuals for two Mathematica programs. The first is a tool for computing the generators of HFT^ and the decategorified tangle invariant ∇ˢ. The second allows us to compute bordered sutured Floer homology using nice diagrams.
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Kneip, Jakob [Verfasser]. "Tangles and where to find them / Jakob Kneip." Hamburg : Staats- und Universitätsbibliothek Hamburg Carl von Ossietzky, 2020. http://d-nb.info/1223095886/34.
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Morshed, Trisha. "THE RELATIONSHIP OF PLAQUES, TANGLES, AND LEWY‐TYPE ALPHA‐SYNUCLEINOPATHY TO VISUAL HALLUCINATIONS IN PARKINSON’S DISEASE AND ALZHEIMER’S DISEASE." Thesis, The University of Arizona, 2015. http://hdl.handle.net/10150/535398.
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A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.Objective: Formed visual hallucinations are a common phenomenon in neurodegenerative disorders such as Parkinson’s Disease (PD), Alzheimer’s disease (AD) and Dementia with Lewy bodies (DLB). While Lewy‐type alpha‐synucleinopathy (LTSis the hallmark neuropathological finding in PD and DLB, amyloid plaques and neurofibrillary tangles are the pathological finding in AD. Previous research has linked complex or formed visual hallucinations (VH) to LTS in neocortical and limbic areas in patients with PD and DLB. As VH also occur in Alzheimer’s disease, and AD pathology often co‐occurs with LTS, we questioned whether this pathology might also be linked to VH. Methods: We performed a semi‐quantitative neuropathological study across brainstem, limbic, and cortical structures in subjects with a documented clinical history of VH and a clinicopathological diagnosis of Parkinson’s disease (PD), Alzheimer’s disease (AD), or dementia with Lewy bodies (DLB). 173 subjects – including 50 with VH and 123 without VH – were selected from the Arizona Study of Aging and Neurodegenerative Disorders. Clinical variables examined included the Mini‐mental State Exam, Hoehn & Yahr stage, and total dopaminergic medication dose. Neuropathological variables examined included total and regional LTS and plaque and tangle densities. Results: A significant relationship was found between the density of LTS and the presence of VH in all diagnostic groups. Plaque and tangle densities also were associated with VH in PD (p=.003 for plaque and p=.004 for tangles), but not in AD, where densities were high regardless of the presence of hallucinations.. Conclusion: Plaques and tangles as well as LTS may contribute to the pathogenesis of VH. Incident VH may be a clinical indicator of underlying pathological events: the development of plaques and tangles in patients with PD, and LTS in patients with AD.
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Suzuki, Sakie. "On the universal sl2 invariant of boundary bottom tangles." 京都大学 (Kyoto University), 2012. http://hdl.handle.net/2433/157739.
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Weißauer, Daniel [Verfasser], and Reinhard [Akademischer Betreuer] Diestel. "On Tangles and Trees / Daniel Weißauer ; Betreuer: Reinhard Diestel." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2018. http://d-nb.info/1166315363/34.
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Weißauer, Daniel Verfasser], and Reinhard [Akademischer Betreuer] [Diestel. "On Tangles and Trees / Daniel Weißauer ; Betreuer: Reinhard Diestel." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2018. http://nbn-resolving.de/urn:nbn:de:gbv:18-92847.
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Su, Tao. "A Hodge-theoretic Study of Augmentation Varieties Associated to Legendrian Knots/Tangles." Thesis, University of California, Berkeley, 2019. http://pqdtopen.proquest.com/#viewpdf?dispub=10824535.
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In this article, we give a tangle approach in the study of Legendrian knots in the standard contact three-space. On the one hand, we define and construct Legenrian isotopy invariants including ruling polynomials and Legendrian contact homology differential graded algebras (LCH DGAs) for Legendrian tangles, generalizing those of Legendrian knots. Ruling polynomials are the Legendrian analogues of Jones polynomials in topological knot theory, in the sense that they satisfy the composition axiom.
On the other hand, we study certain aspects of the Hodge theory of the "representation varieties (of rank 1)" of the LCH DGAs, called augmentation varieties, associated to Legendrian tangles. The augmentation variety (with fixed boundary conditions), hence its mixed Hodge structure on the compactly supported cohomology, is a Legendrian isotopy invariant up to a normalization. This gives a generalization of ruling polynomials in the following sense: the point-counting/weight (or E-) polynomial of the variety, up to a normalized factor, is the ruling polynomial. This tangle approach in particular provides a generalization and a more natural proof to the previous known results of M.Henry and D.Rutherford. It also leads naturally to a ruling decomposition of this variety, which then induces a spectral sequence converging to the MHS. As some applications, we show that the variety is of Hodge-Tate type, show a vanishing result on its cohomology, and provide an example-computation of the MHSs.
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Anumala, Upendra Rao. "Development of selective fluorescent imaging agents for neurofibrillary tangles in Alzheimer’s diagnosis." Phd thesis, TU Darmstadt, 2013. https://tuprints.ulb.tu-darmstadt.de/3718/1/Thesis_Upendra_Rao_Anumala.pdf.
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Alzheimer’s disease (AD) is a neurodegenerative disorder, a form of dementia that worsens over time. With the number of AD patients rising year by year, the total number of patients has already surpassed more than 25 million and this number will grow closer to 63 million by 2030. Symptoms of this disease include memory loss, challenges in problem solving, trouble in understanding visual images or spatial relationships and problems in speaking and writing. Current methods of detection rely on the minimal mental state examination. This is often inaccurate and cannot differentiate between AD and other forms of dementia. The two hallmarks that are responsible for AD are the formation of senile plaques (SPs) and neurofibrillary tangles (NFTs) in the brain. SPs are formed by the aggregation of insoluble amyloid beta protein and NFTs are formed by aggregation of hyperphosphorylated tau protein. In a healthy human brain, these two proteins are produced and broken down to small fragments and eliminated. In AD patients, SPs and NFTs are formed by aggregation of these two proteins.
It is possible to image these SPs and NFTs by techniques such as positron emission tomography (PET) or fluorescence imaging which may enable early diagnosis of AD. Although, SP imaging is known, SP deposition does not correlate with the disease and is observed in healthy patients also, hence, a diagnosis of the disease based solely on SPs imaging is likely to be inaccurate. In addition to this, it is difficult to correlate the disease progression with senile plaque quantity in the brain. On the other hand, NFT formation known to correlate with the disease progression, and therefore, fluorescence imaging of such NFTs may reveal the disease progression.
The present study describes a set of compounds able to visualize NFTs and SPs in a human AD brain obtained at autopsy. Several classes of compounds were synthesized and explored for their ability to stain NFTs, of these; rhodanine-3-acetic acids, 5H-imidazo [4,5-c] pyridine derivatives, bis(arylvinyl)pyrazine derivatives were identified as promising compounds for tau imaging. Our observations with these compounds showed us that thesecompounds bind to NFTs in an AD brain, which were clearly visualized by the fluorescence microscopy. In addition to this, selected compounds were tested for their cytotoxicity in hepatocellular carcinoma cell lines and zebrafish embryo development assay. These cytotoxicity studies indicated that these compounds display no or negligible cytotoxicity. Further, in vitro experiments of rhodanine-3-acetic acid derivatives in P30lS mice retina and in vitro experiments in human AD retina resulted in the absence of staining of retinal tissues. Remarkably, control tissues were stained with AT8 antibody. These results suggest that the tau aggregates in the retina of P301S mice are different from human tau deposits present in hyperphosphorylated NFTs. Further, in vitro experiments with 5H-imidazo [4,5-c] pyridine derivatives on olfactory epithelium tissues visualized tau deposits in olfactory epithelium tissues.
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Kurt, Mustafa Ayberk. "The ultrastructure and immunochemistry of Alzheimer's disease neuropathology : investigation of human biopsy and mouse model brains." Thesis, St George's, University of London, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313785.
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Schmutzler, Sandra. "Die potentielle neuroprotektive Funktion Perineuronaler Netze gegenüber Tau-Protein-Hyperphosphorylierungen und neurofibrillären Tangles in einem Mausmodell der Frontotemporalen Demenz (P301L)." Doctoral thesis, Universitätsbibliothek Leipzig, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-142626.
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Perineuronale Netze (PN) sind eine spezialisierte Form der neuronalen extrazellulären Matrix. Es wird vermutet, dass sie neuroprotektive Eigenschaften besitzen und die von ihnen umschlossenen Neurone gegenüber Degeneration schützen. Mehrere Studien untersuchten bereits die PN in Zusammenhang mit der Pathologie der Alzheimer-Erkrankung. Für die Frontotemporalen Demenzen, die nach der Alzheimer-Erkrankung und der vaskulären Demenz zu den häufigsten dementiellen Erkrankungen gehören, ist die Beziehung von PN und Tau-Protein (TP)-Pathologie noch nicht untersucht worden.
Die Dissertation beschäftigt sich mit der Korrelation von netztragenden Neuronen mit TP-Pathologie in einem Mausmodel der Frontotemporalen Demenz mit Parkinsonismus des Chromosoms 17 (FTDP-17). Sie geht der Frage nach, ob netztragende Neuronen vor Degeneration und intrazellulären Ablagerungen von verändertem TP, in Form von Hyperphosphorylierungen (HP) und Neurofibrillären Tangles (NFT), geschützt sind. Mit Hilfe immunhistochemischer Fluoreszenzmarkierung und Western Blot wurden die Gehirne transgener Mäuse mit der P301L-Mutation des TP im Alter von drei und achteinhalb Monaten untersucht. Dabei wurden sechs Hirnregionen ausgewählt: Primärer Somatosensorischer Kortex (PSC), Entorhinaler Kortex (EC), Hippokampus (Hipp), Pars magnocellularis des Nucleus ruber (NR-m), Pars reticulata der Substantia nigra (SN-r) und Motorischer Trigeminuskern (Mo5).
Die Untersuchungen zeigen, dass die PN bei der FTDP-17 die Neurone nicht explizit vor TP-Pathologie schützen. Jedoch kommt es zu keiner signifikanten Reduktion der netztragenden Zellen im Altersgang, sodass eine neuroprotektive Funktion der PN weiterhin vermutet werden kann.
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Tora, Veronica <1987>. "Mathematical models for brain diseases: formation of senile plaques and neurofibrillary tangles in Alzheimer's disease." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2019. http://amsdottorato.unibo.it/9040/1/tora_veronica_tesi.pdf.
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Alzheimer’s disease (AD) is characterized by the presence of two specific structures in brain of patients: senile plaques (SP) and neurofibrillary tangles (NTFs). Oligomers of beta amyloid protein are the main component of SP, while NFTs are constituted by oligomers of hyperphosphorylated tau protein. The aim of this thesis is to present two studies concerning the process of diffusion and agglomeration of tau protein first into fibrils and eventually up to neurofibrillary tangles. The aforesaid researches share the use of Smoluchowski-type equations (including diffusion and monomers production) on a finite weighted graph, which is conceived as a theoretical approximation of the human brain, where each vertex represents a cerebral area of interest, while the connections between them are described by the edges. In the first chapter, we present a model for the aggregation and diffusion of hyperphosphorylated tau based on a finite dimensional Smoluchowski-type system on a finite graph, aimed at reproducing tau patterns obtained through suitable in vivo measurements. In such model, clusters whose length exceeds an a priori established critical threshold are defined to be tangles. Statistical analysis is performed, comparing the model-predicted tau concentrations (in monomeric, oligomeric form and in tangles) with cortical atrophy data and tau measurements in AD patients provided by in vivo neuroimaging. The second research considers the process of aggregation in tangles of hyperphosphorylated tau protein as a result of a coagulation process of this protein. The formation of neurofibrillary tangles is mathematically characterized in terms of a sol-gel phase transition for a polymerization problem, modelled by means of infinite dimensional Smoluchowski-type system on a finite graph. The process of formation of gel is a suitable tool for the description of the formation of neurofibrillary tangles, since it allows one to provide insights on the nature of this phenomenon in AD scenario.
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Kurkofka, Jan Verfasser], and Reinhard [Akademischer Betreuer] [Diestel. "Ends and tangles, stars and combs, minors and the Farey graph / Jan Kurkofka ; Betreuer: Reinhard Diestel." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2020. http://nbn-resolving.de/urn:nbn:de:gbv:18-106601.
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Kurkofka, Jan [Verfasser], and Reinhard [Akademischer Betreuer] Diestel. "Ends and tangles, stars and combs, minors and the Farey graph / Jan Kurkofka ; Betreuer: Reinhard Diestel." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2020. http://d-nb.info/1216998116/34.
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Hussey, Susan. "Studies on the preparation and properties of neurofibrillary tangles from brains of patients with Alzheimer-type dementia." Thesis, University of Edinburgh, 1988. http://hdl.handle.net/1842/18978.
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Alzheimer's disease and senile dementia of the Alzheimer type (Alzheimer-type dementia, ATD) are progressive dementing illnesses characterised histopathologically by the presence of neurofibrillary tangles and plaques. Ultrastructurally tangles are composed of paired helical filaments (PHF) (Kidd, 1963) of unknown origin. The purpose of this study was to investigate the biochemical and biophysical properties of tangles, and their constituent PHF. Investigation of tangle solubility by quantitative light microscopy of brain homogenates showed that a proportion of tangles, which varied between brains (ATD and Down's Syndrome with ATD pathology) were soluble in sodium dodecylsulphate (SDS) and NaOH. Tangle solubility in 1&37 SDS was inversely related to duration of dementia suggesting that patients with a long standing illness have more fragile tangles. Ultrastructural studies were carried out on tangle enriched fractions prepared by ultracentrifugation of supernatants from SDS treated brain homogenates and by sucrose density gradient centrifugation of brain homogenates not treated with SDS. PHF in the former preparation were found to be longer with lengthened pitches compared to PHF in the latter preparation. PHF from another SDS treated preparation which was repeatedly freeze thawed (up to 25oC) were observed to lose their their helical configuration. These electronmicroscopic observations suggest that the helical substructure of PHF can be subject to conformational change, whilst filament structure is retained. Preparation of tangle enriched fractions from ATD brains was investigated using Percoll, sucrose gradient centrifugation and fluorescence activated cell sorting (FACS). Percoll proved unsatisfactory; and sucrose gradient centrifugation was used to prepare fractions enriched in tangles from ATD brains, and control fractions prepared in the same way, from control brains. Tangle preparation using FACS was a new technique, whereby tangles labelled with the fluorescent dye, congo red, could be sorted from ATD brain homogenate. Partially purified tangle preparations were investigated using spectroscopy. The resulting spectra showed features consistent with an increase in β sheet in the tangle enriched versus the control fraction.
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Branca, Caterina, Darren M. Shaw, Ramona Belfiore, Vijay Gokhale, Arthur Y. Shaw, Christopher Foley, Breland Smith, et al. "Dyrk1 inhibition improves Alzheimer's disease-like pathology." WILEY, 2017. http://hdl.handle.net/10150/626504.
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There is an urgent need for the development of new therapeutic strategies for Alzheimer's disease (AD). The dual-specificity tyrosine phosphorylation-regulated kinase-1A (Dyrk1a) is a protein kinase that phosphorylates the amyloid precursor protein (APP) and tau and thus represents a link between two key proteins involved in AD pathogenesis. Furthermore, Dyrk1a is upregulated in postmortem human brains, and high levels of Dyrk1a are associated with mental retardation. Here, we sought to determine the effects of Dyrk1 inhibition on AD-like pathology developed by 3xTg-AD mice, a widely used animal model of AD. We dosed 10-month-old 3xTg-AD and nontransgenic (NonTg) mice with a Dyrk1 inhibitor (Dyrk1-inh) or vehicle for eight weeks. During the last three weeks of treatment, we tested the mice in a battery of behavioral tests. The brains were then analyzed for the pathological markers of AD. We found that chronic Dyrk1 inhibition reversed cognitive deficits in 3xTg-AD mice. These effects were associated with a reduction in amyloid-beta (Ab) and tau pathology. Mechanistically, Dyrk1 inhibition reduced APP and insoluble tau phosphorylation. The reduction in APP phosphorylation increased its turnover and decreased Ab levels. These results suggest that targeting Dyrk1 could represent a new viable therapeutic approach for AD.
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Genfors, Björn. "siRNA knockdown of Tau kinases in primary neurons." Thesis, KTH, Skolan för bioteknologi (BIO), 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-149472.
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Barrett, Alexander Steven. "Structural Basis for Ternary Complex Formation Between tau, Hsp90, and FKBP51." Scholar Commons, 2013. http://scholarcommons.usf.edu/etd/4436.
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The accumulation of the microtubule associated protein tau has been implicated in several neurological disorders; however, its interaction with chaperones along its normal degradation pathway remains largely uncharacterized at single residue resolution. In this study, nuclear magnetic resonance (NMR) spectroscopy was used to probe the interaction between tau, the molecular chaperone Hsp90, and the immunophilin FKBP51. Resonance intensity changes were observed for specific residues in the heteronuclear single quantum coherence (HSQC) spectra of 15N-labeled tau in the presence of Hsp90 and/or FKBP51. Analysis of the HSQC spectra identified the two hydrophobic hexapeptide motifs located at residues V275 - K280 and V306 - K311 in tau's C-terminal assembly domain as the sites of an interaction with both Hsp90 and FKBP51. Resonances that show reduced intensities did not experience line broadening, which suggests that slow chemical exchange is occurring with a bound conformation that is not observable due to the molecular weight of the complex. We have also investigated the role of the PPIase domain alone in binding to tau and found that specific residues within the PPIase active site experience significant reductions in intensity upon addition of tau. The experimental data is collectively used to propose a structural model for ternary complex formation between tau, Hsp90, and FKBP51.
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Pickett, Eleanor Kay. "Synapse dysfunction in Alzheimer's disease : contributions of amyloid-beta and tau." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/31343.
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Alzheimer's disease (AD) is characterised by memory loss, insidious cognitive decline, profound neurodegeneration, and the extracellular accumulation of amyloid-beta (Aβ) peptide in senile plaques and intracellular accumulation of tau in neurofibrillary tangles. Synaptic dysfunction and loss is the strongest pathological correlate of cognitive decline in AD with increasing evidence implicating neuropathological forms of both amyloid-beta and tau protein in this process. A large amount of evidence suggests that oligomeric forms of Aβ, associated with senile plaques, are toxic to synapses but the precise localisation of Aβ and which forms are synaptotoxic remain unknown. Using the high-resolution technique, array tomography, this thesis characterised the synaptic localisation of different forms of Aβ oligomers in a mouse model of amyloidopathy. These results show that different oligomeric Aβ species are present in both presynapses and postsynapses. This study highlights the potential of array tomography for rapid testing of aggregation state specific Aβ antibodies in brain tissue. Following these results, the presence of tau at synapses was examined. Despite the knowledge that tau spreads through defined synaptic circuits, it is currently unknown whether synapse loss occurs before the accumulation of tau or as a consequence. To address this, array tomography was used to examine a mouse model in which mutant P301L human tau is expressed primarily in the entorhinal cortex (rTgTauEC). It has previously been shown that rTgTauEC mice exhibit neuronal loss in the entorhinal cortex and synapse density loss in the middle molecular layer (MML) of the dentate gyrus at 24 months of age. The density of tau-expressing and total presynapses, and the spread of tau into the postsynapse in the MML of 3-6, 9, and 18 month old mice were examined. No loss of synapse density was observed in the MML up to 18 months of age, even in axons expressing tau. Despite the maintenance of synapse density, we see spread of human tau from presynaptic terminals to postsynaptic compartments in the MML at very early ages. This indicates that the spread of tau through neural circuits is not due to the degeneration of axon terminals and is an early feature of the disease process. Following examination of both synaptic amyloid-beta and tau in separate models, this thesis then examined how these two proteins may be synergistically working together to drive synaptic pathology. To investigate this a novel mouse model was used in which amyloid-beta deposits are present in combination with non-mutated human tau expression (APP/PS1 + hTau). These results suggested that the addition of human tau expression does not increase plaque associated synapse loss, neither does it increase the proportion of synapses colocalising with amyloid-beta. Similarly the presence of human tau at individual postsynapses was not enhanced in the presence of oligomeric Aβ. Surprisingly, intact long-term recognition memory was observed in APP/PS1 + hTau mice. However a hyperactive phenotype was detected in these mice that could be prevented upon tau suppression. This suggests a synergistic relationship may exist in the presentation of this phenotype. Finally in the last part of this thesis, synapses from post-mortem human Alzheimer's disease and age-matched controls were investigated. It has previously been suggested that both amyloid-beta and tau can interfere with mitochondrial transport to the synapse and mitochondrial function. For this reason the presence of synaptic mitochondria at both the presynapse and postsynapse was determined in order to investigate any alteration in the diseased state. A reduction in the proportion of presynapses with multiple mitochondria present was detected in anterior/posterior transverse temporal cortex (BA41/42). This was not observed in dorsolateral prefrontal cortex (BA46), suggesting either a selective vulnerability of the former brain region or a selective resistance of the latter brain region, to mitochondrial depletion at the synapse. The findings presented in this thesis demonstrate that when investigated in isolation, pathological forms of amyloid-beta are present at a subset of synapses where they may contribute to toxicity, whilst the spread of tau protein is an early feature of the disease process and occurs prior to overt synapse loss. This thesis also explores the proposed synergistic relationship between amyloid-beta and tau using a novel mouse model and human post-mortem brain tissue. Since these two proteins both have been implicated in synaptic dysfunction, investigating Aβ and tau in new mouse models and human brain tissue will be instrumental in furthering our understanding of mechanisms and features of synaptotoxicity that could be important therapeutic targets.
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Pham, Van Anh. "Loop Numbers of Knots and Links." TopSCHOLAR®, 2017. http://digitalcommons.wku.edu/theses/1952.
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This thesis introduces a new quantity called loop number, and shows the conditions in which loop numbers become knot invariants. For a given knot diagram D, one can traverse the knot diagram and count the number of loops created by the traversal. The number of loops recorded depends on the starting point in the diagram D and on the traversal direction. Looking at the minimum or maximum number of loops over all starting points and directions, one can define two positive integers as loop numbers of the diagram D. In this thesis, the conditions under which these loop numbers become knot invariants are identified. In particular, the thesis answers the question when these numbers are invariant under flypes in the diagram D.
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Price, Candice Renee. "A biological application for the oriented skein relation." Diss., University of Iowa, 2012. https://ir.uiowa.edu/etd/3369.
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The traditional skein relation for the Alexander polynomial involves an oriented knot, K+, with a distinguished positive crossing; a knot K−, obtained by changing the distinguished positive crossing of K+ to a negative crossing; and a link K0, the orientation preserving resolution of the distinguished crossing. We refer to (K+,K−,K0) as the oriented skein triple.
A tangle is defined as a pair (B, t) of a 3-dimensional ball B and a collection of disjoint, simple, properly embedded arcs, denoted t. DeWitt Sumners and Claus Ernst developed the tangle model which uses the mathematics of tangles to model DNA-protein binding. The protein is seen as the 3-ball and the DNA bound by the protein as properly embedded curves in the 3-ball. Topoisomerases are proteins that break one segment of DNA allowing a DNA segment to pass through before resealing the break. Effectively, the action of these proteins can be modeled as K− ↔ K+. Recombinases are proteins that cut two segments of DNA and recombine them in some manner. While recombinase local action varies, most are mathematically equivalent to a resolution, i.e. K± ↔ K0. The oriented triple is now viewed as K− = circular DNA substrate, K+ = product of topoisomerase action, K0 = product of recombinase action.
The theorem stated in this dissertation gives a relationship between two 2-bridge knots, K+ and K−, that differ by a crossing change and a link, K0 created from the oriented resolution of that crossing. We apply this theorem to difference topology experiments using topoisomerase proteins to study SMC proteins.
In recent years, link homology theories have become a popular invariant to develop and study. One such invariant knot Floer homology, was constructed by Peter Ozsváth, Zoltán Szabó, and independently Jacob Rasmussen, denoted by HFK. It is also a refinement of a classical invariant, the Alexander polynomial.
The study of DNA knots and links are of great interest to molecular biologists as they are present in many cellular process. The variety of experimentally observed DNA knots and links makes separating and categorizing these molecules a critical issue. Thus, knowing the knot Floer homology will provide restrictions on knotted and linked products of protein action.
We give a summary of the combinatorial version of knot Floer homology from known work, providing a worked out example. The thesis ends with reviewing knot Floer homology properties of three particular sub-families of biologically relevant links known as (2, p)- torus links, clasp knots and 3-strand pretzel links.
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Distl, Roland. "Filipin-Darstellung des Cholesterins der Tangle-tragenden Neurone in Gehirnen von Patienten mit Alzheimer- und Niemann-Pick-Typ-C-Krankheit." Doctoral thesis, [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=969501110.
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Anumala, Upendra Rao [Verfasser], Boris [Akademischer Betreuer] Schmidt, and Harald [Akademischer Betreuer] Kolmar. "Development of selective fluorescent imaging agents for neurofibrillary tangles in Alzheimer’s diagnosis / Upendra Rao Anumala. Betreuer: Boris Schmidt ; Harald Kolmar." Darmstadt : Universitäts- und Landesbibliothek Darmstadt, 2013. http://d-nb.info/1108093981/34.
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Ahlquist, Mari. "On Knots and DNA." Thesis, Linköpings universitet, Matematiska institutionen, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-144294.
Full textAbstract:
Knot theory is the mathematical study of knots. In this thesis we study knots and one of its applications in DNA. Knot theory sits in the mathematical field of topology and naturally this is where the work begins. Topological concepts such as topological spaces, homeomorphisms, and homology are considered. Thereafter knot theory, and in particular, knot theoretical invariants are examined, aiming to provide insights into why it is difficult to answer the question "How can we tell knots appart?". In knot theory invariants such as the bracket polynomial, the Jones polynomial and tricolorability are considered as well as other helpful results like Seifert surfaces. Lastly knot theory is applied to DNA, where it will shed light on how certain enzymes interact with the genome.
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Platt, Thomas. "LEPTIN RESISTANCE INDUCED OBESITY AND DIABETES PROMOTE NEUROPATHOLOGICAL CHANGES IN THE AGING BRAIN." UKnowledge, 2014. http://uknowledge.uky.edu/biochem_etds/18.
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The aging brain is prone to the development of pathology and dementia. With a rapidly growing elderly population diagnoses of neurodegenerative diseases, such as Alzheimer’s disease (AD), frontotemporal dementia (FTD), and Parkinson’s disease are on the rise. Additionally, diabetes and obesity are linked to an increased risk of dementia. The convergence of this increasingly aged population with the obesity and diabetes epidemic give rise to new concerns regarding the future of prevention and treatment of neurodegenerative diseases. Our lab has previously shown that leptin, an adipokine involved in signaling satiety to the hypothalamus, can modulate the generation of the amyloid beta (Aβ) peptide (a toxic peptide associated with neurologic disease) and attenuate hyperphosphorylation of the tau protein (another peptide prone to forming large insoluble structures causing neurodegeneration). From these studies we have elucidated that leptin resistant mice (which develop severe obesity and type-2 diabetes mellitus) with knock-in mutations for the amyloid precursor protein (APP) and presenilin-1 (PS1) genes develop extensive vascular pathology and cognitive impairments. Interestingly, these mice do not display increased levels of amyloid deposition in the brain. Additionally, increased tau phosphorylation occurs in these mice with leptin resistance. As a follow up to this study db mice were transduced, via adeno-associated virus, with the tau P301L mutant to induce the development of tangle pathology. These mice displayed no cognitive deficits, yet they displayed increases in both tau phosphorylation and tangle count within the hippocampus. Collectively, these studies indicate leptin resistance, obesity, and type-2 diabetes mellitus promote the development of cerebrovascular and neurofibrillary tangle pathologies associated with neurodegeneration and dementia. These observations open many previously unexplored avenues for developing novel therapeutics to treat these devastating diseases.
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Meier, Shelby. "PATHOLOGICAL TAU AS A CAUSE, AND CONSEQUENCE, OF CELLULAR DYSFUNCTION." UKnowledge, 2019. https://uknowledge.uky.edu/physiology_etds/44.
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Tauopathies are a group of neurodegenerative diseases characterized by the abnormal deposition of the protein tau, a microtubule stabilizing protein. Under normal physiological conditions tau is a highly soluble protein that is not prone to aggregation. In disease states alterations to tau lead to enhanced fibril formation and aggregation, eventually forming neurofibrillary tangles (NFTs). The exact cause for NFT deposition is unknown, but increased post-translational modifications and mutations to the tau gene can increase tangle formation.
Tauopathic brains are stuck in a detrimental cycle, with cellular dysfunction contributing to the development of tau pathology and the development of tau pathology contributing to cellular dysfunction. The exact mechanisms by which each part of the cycle contributes to the other are still being explored. To investigate the unique contributions of each part of this cycle we utilized two separate models of tauopathy: one chronic and one acute. Overall this project provides novel insight into the role of pathological tau as both a cause, and a consequence, of cellular dysfunction.
To understand how development of tau pathology contributes to cellular dysfunction we studied chronic disease models. Using human brain tissue we found that under normal conditions tau associates with ribosomes but that this interaction is enhanced in Alzheimer’s disease brains. We then used in vitro and in vivo models of tauopathy to show that this association causes a decrease in protein synthesis. Finally, we show that wild type tau and mutant tau reduce protein translation to similar levels.
To understand how general cellular dysfunction contributes to development of pathology we used an acute model of tauopathy through traumatic brain injury (TBI). We injured rTg4510 tau transgenic mice at different ages to investigate the effect of TBI on tau fibrillization (2 month old) and the effect of TBI on tau already in NFTs (4.5 month old). In 2 month old mice, we found that tau hyperphosphorylation was decreased at 24 hours and increased at 7 days post injury, and that tau oligomerization was decreased at 24 hours post injury. We also found that tau fibrillization was not increased after 24 hours or 7 days post injury. In 4.5 month old mice, we found that TBI did not increase or decrease tangle counts in the brain, but we did qualitatively observe decreased variability within groups.
Overall these studies contribute novel understanding of tau’s role in different disease states. We identified a functional consequence of the interaction between tau and ribosomes, and demonstrated that a single head impact did not increase tau fibril formation within 7 days of injury. While human diseases associated with TBI show neurofibrillary tangle deposition, we have yet to recreate that aspect of the disease in research models of TBI. Our findings support the need for further investigation into the nuances of tau in disease, especially following TBI.
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Brun-Salabert, Anne-Sophie. "Développement préclinique de sondes fluorées utilisées dans l'imagerie moléculaire des pathologies neurodégénératives." Thesis, Toulouse 3, 2015. http://www.theses.fr/2015TOU30371/document.
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Les mécanismes physiopathologiques liés aux maladies neurodégénératives restent encore largement méconnus. Deux processus semblent être particulièrement en cause dans les phénomènes de neurodégénérescence : la neurotoxicité par afflux massif de calcium due à une activation excessive des récepteurs NMDA (GluN) et la neurotoxicité par déstabilisation du cytosquelette du neurone par le biais de la phosphorylation anormale de la protéine tau. L'imagerie moléculaire par le biais de la tomographie par émission de positons (TEP) et de radiotraceurs, en étudiant les mécanismes moléculaires in vivo, permet de détecter et quantifier ces phénomènes. Ce travail a eu pour objet d'étudier un dérivé de la mémantine, un antagoniste des GluN se fixant sur un site intra-canal accessible uniquement lorsque ces récepteurs sont activés ce qui en fait donc un vecteur d'imagerie intéressant pour étudier leur activation. Nous avons mis au point la synthèse d'un nouveau radiotraceur dérivé de la mémantine : la [18F]-FNM (Fluoroéthylnormémantine). Il s'agit d'une synthèse par substitution nucléophile d'un groupement tosylate par du [18F], suivie d'une hydrolyse acide. Cette synthèse est reproductible avec un rendement de 10%, son activité spécifique est > 355 GBq/µmol. Chez le rat, le traceur passe la barrière hémato-encéphalique et sa distribution cérébrale est bien corrélée avec la localisation des GluN (r=0.622, p<0.0001). Sa cinétique de fixation (40 minutes) est compatible avec son utilisation en TEP. En ce qui concerne les tauopathies, la protéine tau stabilise l'organisation microtubulaire. Lors d'une phosphorylation anormale, l'interaction avec les microtubules diminue et les protéines tau vont s'accumuler en formant des Paires de Filaments en Hélice (PHF). Nous avons optimisé la radiosynthèse de l' [18F]-AV1451 ciblant les PHF. Notre rendement de synthèse est de 30% et l'activité spécifique du traceur > 10 GBq/µmol. Nous avons réalisé des autoradiographies sur des coupes de cerveaux atteints de tauopathie et nous avons constaté la capacité du traceur à différencier les coupes saines des coupes malades. La production de cet outil dans notre centre va nous permettre d'étudier la présence de PHF chez le marmouset, un primate particulièrement intéressant dans l'étude du vieillissement. Nous avons donc réalisé la synthèse de deux radiotraceurs innovants : la [18F]-FNM et le [18F]-AV1451, les synthèses sont reproductibles et les rendements compatibles avec des productions de doses en recherche pré-clinique et cliniqueThe pathophysiological mechanisms associated with neurodegenerative diseases remain largely unknown. Two processes appear to be particularly involved in the phenomena of neurodegeneration: neurotoxicity induced by massive influx of calcium caused by excessive activation of NMDA receptors (GluN) and neurotoxicity by destabilization of neuron cytoskeleton through abnormal protein tau phosphorylation. Molecular imaging through positron emission tomography (PET) and radiotracers, by studying the molecular mechanisms in vivo, allows to detect and quantify these phenomena. This work was intended to study a memantine derivative, a GluN antagonist. We chose to develop a ligand that selectively binds to the ion channel in the open and active state which therefore makes it an interesting vector to study their overactivation. We have developed the synthesis of a new memantine analogue radiotracer: the [18F]-FNM (Fluoroéthylnormémantine). This is a synthesis by nucleophilic substitution of a tosylate with [18F], followed by acid hydrolysis. This synthesis is reproducible with a yield of 10%, its specific activity was> 355 GBq / µmol. In rats, the tracer cross the blood-brain barrier and brain distribution correlates well with the location of GluN (r = 0.622, p <0.0001). The binding kinetics (40 minutes) is compatible with its use in PET. Regarding tauopathies, the tau protein stabilizes microtubule organization. During abnormal phosphorylation, interaction with microtubules and tau proteins decreases and tau will accumulate to form Paired helical Filament (PHF). We optimized the radiosynthesis of [18F] AV1451 targeting 3 tau PHF. Our yield of synthesis is 30% and the specific activity of the tracer> 10 GBq / µmol. We made autoradiography on brains sections and have shown tracer ability to differentiate healthy and pathological slices. This tool will allow us to study the presence of PHF in marmosets, a particularly interesting primate in the study of aging. So we performed the synthesis of two innovative radiotracers: the [18F]-FNM and [18F]-AV1451, syntheses are reproducible and yields compatible with doses manufacturing in pre-clinical and clinical research
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Yu, Shona Huimin. "The Cyclotomic Birman-Murakami-Wenzl Algebras." Thesis, The University of Sydney, 2007. http://hdl.handle.net/2123/3560.
Full textAbstract:
This thesis presents a study of the cyclotomic BMW algebras, introduced by Haring-Oldenburg as a generalization of the BMW (Birman-Murakami-Wenzl) algebras related to the cyclotomic Hecke algebras of type G(k,1,n) (also known as Ariki-Koike algebras) and type B knot theory involving affine/cylindrical tangles. The motivation behind the definition of the BMW algebras may be traced back to an important problem in knot theory; namely, that of classifying knots (and links) up to isotopy. The algebraic definition of the BMW algebras uses generators and relations originally inspired by the Kauffman link invariant. They are intimately connected with the Artin braid group of type A, Iwahori-Hecke algebras of type A, and with many diagram algebras, such as the Brauer and Temperley-Lieb algebras. Geometrically, the BMW algebra is isomorphic to the Kauffman Tangle algebra. The representations and the cellularity of the BMW algebra have now been extensively studied in the literature. These algebras also feature in the theory of quantum groups, statistical mechanics, and topological quantum field theory. In view of these relationships between the BMW algebras and several objects of "type A", several authors have since naturally generalized the BMW algberas for other types of Artin groups. Motivated by knot theory associated with the Artin braid group of type B, Haring-Oldenburg introduced the cyclotomic BMW algebras B_n^k as a generalization of the BMW algebras such that the Ariki-Koike algebra h_{n,k} is a quotient of B_n^k, in the same way the Iwahori-Hecke algebra of type A is a quotient of the BMW algebra. In this thesis, we investigate the structure of these algebras and show they have a topological realization as a certain cylindrical analogue of the Kauffman Tangle algebra. In particular, they are shown to be R-free of rank k^n (2n-1)!! and bases that may be explicitly described both algebraically and diagrammatically in terms of cylindrical tangles are obtained. Unlike the BMW and Ariki-Koike algebras, one must impose extra so-called "admissibility conditions" on the parameters of the ground ring in order for these results to hold. This is due to potential torsion caused by the polynomial relation of order k imposed on one of the generators of B_n^k. It turns out that the representation theory of B_2^k is crucial in determining these conditions precisely. The representation theory of B_2^k is analysed in detail in a joint preprint with Wilcox in [45] (http://arxiv.org/abs/math/0611518). The admissibility conditions and a universal ground ring with admissible parameters are given explicitly in Chapter 3. The admissibility conditions are also closely related to the existence of a non-degenerate Markov trace function of B_n^k which is then used together with the cyclotomic Brauer algebras in the linear independency arguments contained in Chapter 4. Furthermore, in Chapter 5, we prove the cyclotomic BMW algebras are cellular, in the sense of Graham and Lehrer. The proof uses the cellularity of the Ariki-Koike algebras (Graham-Lehrer [16] and Dipper-James-Mathas [8]) and an appropriate "lifting" of a cellular basis of the Ariki-Koike algebras into B_n^k, which is compatible with a certain anti-involution of B_n^k. When k = 1, the results in this thesis specialize to those previously established for the BMW algebras by Morton-Wasserman [30], Enyang [9], and Xi [47]. REMARKS: During the writing of this thesis, Goodman and Hauschild-Mosley also attempt similar arguments to establish the freeness and diagram algebra results mentioned above. However, they withdrew their preprints ([14] and [15]), due to issues with their generic ground ring crucial to their linear independence arguments. A similar strategy to that proposed in [14], together with different trace maps and the study of rings with admissible parameters in Chapter 3, is used in establishing linear independency of our basis in Chapter 4. Since the submission of this thesis, new versions of these preprints have been released in which Goodman and Hauschild-Mosley use alternative topological and Jones basic construction theory type arguments to establish freeness of B_n^k and an isomorphism with the cyclotomic Kauffman Tangle algebra. However, they require their ground rings to be an integral domain with parameters satisfying the (slightly stronger) admissibility conditions introduced by Wilcox and the author in [45]. Also, under these conditions, Goodman has obtained cellularity results. Rui and Xu have also obtained freeness and cellularity results when k is odd, and later Rui and Si for general k, under the assumption that \delta is invertible and using another stronger condition called "u-admissibility". The methods and arguments employed are strongly influenced by those used by Ariki, Mathas and Rui [3] for the cyclotomic Nazarov-Wenzl algebras and involve the construction of seminormal representations; their preprints have recently been released on the arXiv. It should also be noted there are slight differences between the definitions of cyclotomic BMW algebras and ground rings used, as explained partly above. Furthermore, Goodman and Rui-Si-Xu use a weaker definition of cellularity, to bypass a problem discovered in their original proofs relating to the anti-involution axiom of the original Graham-Lehrer definition. This Ph.D. thesis, completed at the University of Sydney, was submitted September 2007 and passed December 2007.
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Yu, Shona Huimin. "The Cyclotomic Birman-Murakami-Wenzl Algebras." School of Mathematics and Statistics, 2007. http://hdl.handle.net/2123/3560.
Full textAbstract:
Doctor of PhilosophyThis thesis presents a study of the cyclotomic BMW algebras, introduced by Haring-Oldenburg as a generalization of the BMW (Birman-Murakami-Wenzl) algebras related to the cyclotomic Hecke algebras of type G(k,1,n) (also known as Ariki-Koike algebras) and type B knot theory involving affine/cylindrical tangles. The motivation behind the definition of the BMW algebras may be traced back to an important problem in knot theory; namely, that of classifying knots (and links) up to isotopy. The algebraic definition of the BMW algebras uses generators and relations originally inspired by the Kauffman link invariant. They are intimately connected with the Artin braid group of type A, Iwahori-Hecke algebras of type A, and with many diagram algebras, such as the Brauer and Temperley-Lieb algebras. Geometrically, the BMW algebra is isomorphic to the Kauffman Tangle algebra. The representations and the cellularity of the BMW algebra have now been extensively studied in the literature. These algebras also feature in the theory of quantum groups, statistical mechanics, and topological quantum field theory. In view of these relationships between the BMW algebras and several objects of "type A", several authors have since naturally generalized the BMW algberas for other types of Artin groups. Motivated by knot theory associated with the Artin braid group of type B, Haring-Oldenburg introduced the cyclotomic BMW algebras B_n^k as a generalization of the BMW algebras such that the Ariki-Koike algebra h_{n,k} is a quotient of B_n^k, in the same way the Iwahori-Hecke algebra of type A is a quotient of the BMW algebra. In this thesis, we investigate the structure of these algebras and show they have a topological realization as a certain cylindrical analogue of the Kauffman Tangle algebra. In particular, they are shown to be R-free of rank k^n (2n-1)!! and bases that may be explicitly described both algebraically and diagrammatically in terms of cylindrical tangles are obtained. Unlike the BMW and Ariki-Koike algebras, one must impose extra so-called "admissibility conditions" on the parameters of the ground ring in order for these results to hold. This is due to potential torsion caused by the polynomial relation of order k imposed on one of the generators of B_n^k. It turns out that the representation theory of B_2^k is crucial in determining these conditions precisely. The representation theory of B_2^k is analysed in detail in a joint preprint with Wilcox in [45] (http://arxiv.org/abs/math/0611518). The admissibility conditions and a universal ground ring with admissible parameters are given explicitly in Chapter 3. The admissibility conditions are also closely related to the existence of a non-degenerate Markov trace function of B_n^k which is then used together with the cyclotomic Brauer algebras in the linear independency arguments contained in Chapter 4. Furthermore, in Chapter 5, we prove the cyclotomic BMW algebras are cellular, in the sense of Graham and Lehrer. The proof uses the cellularity of the Ariki-Koike algebras (Graham-Lehrer [16] and Dipper-James-Mathas [8]) and an appropriate "lifting" of a cellular basis of the Ariki-Koike algebras into B_n^k, which is compatible with a certain anti-involution of B_n^k. When k = 1, the results in this thesis specialize to those previously established for the BMW algebras by Morton-Wasserman [30], Enyang [9], and Xi [47]. REMARKS: During the writing of this thesis, Goodman and Hauschild-Mosley also attempt similar arguments to establish the freeness and diagram algebra results mentioned above. However, they withdrew their preprints ([14] and [15]), due to issues with their generic ground ring crucial to their linear independence arguments. A similar strategy to that proposed in [14], together with different trace maps and the study of rings with admissible parameters in Chapter 3, is used in establishing linear independency of our basis in Chapter 4. Since the submission of this thesis, new versions of these preprints have been released in which Goodman and Hauschild-Mosley use alternative topological and Jones basic construction theory type arguments to establish freeness of B_n^k and an isomorphism with the cyclotomic Kauffman Tangle algebra. However, they require their ground rings to be an integral domain with parameters satisfying the (slightly stronger) admissibility conditions introduced by Wilcox and the author in [45]. Also, under these conditions, Goodman has obtained cellularity results. Rui and Xu have also obtained freeness and cellularity results when k is odd, and later Rui and Si for general k, under the assumption that \delta is invertible and using another stronger condition called "u-admissibility". The methods and arguments employed are strongly influenced by those used by Ariki, Mathas and Rui [3] for the cyclotomic Nazarov-Wenzl algebras and involve the construction of seminormal representations; their preprints have recently been released on the arXiv. It should also be noted there are slight differences between the definitions of cyclotomic BMW algebras and ground rings used, as explained partly above. Furthermore, Goodman and Rui-Si-Xu use a weaker definition of cellularity, to bypass a problem discovered in their original proofs relating to the anti-involution axiom of the original Graham-Lehrer definition. This Ph.D. thesis, completed at the University of Sydney, was submitted September 2007 and passed December 2007.
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Schmutzler, Sandra [Verfasser], Thomas [Akademischer Betreuer] Arendt, Markus [Akademischer Betreuer] Morawski, and unbekannt [Gutachter] unbekannt. "Die potentielle neuroprotektive Funktion Perineuronaler Netze gegenüber Tau-Protein-Hyperphosphorylierungen und neurofibrillären Tangles in einem Mausmodell der Frontotemporalen Demenz (P301L) / Sandra Schmutzler ; Gutachter: unbekannt unbekannt ; Thomas Arendt, Markus Morawski." Leipzig : Universitätsbibliothek Leipzig, 2014. http://d-nb.info/1238601715/34.
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Edler, Melissa K. "Alzheimer's disease pathology in aged chimpanzees." Kent State University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=kent1461401487.
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Paula, Vanessa de Jesus Rodrigues de. "Efeitos do lítio sobre a expressão e atividade das enzimas fosfolipase A2 e glicogênio sintase quinase 3beta e sua relação com o estado de fosforilação da proteína tau." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/5/5142/tde-26102015-143450/.
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O presente estudo comparou o efeito do tratamento crônico com lítio em doses subterapêuticas (0,02mM e 0,2mM) e dose terapêutica (2mM) em cultura primária de neurônios corticais e hipocampais. As amostras foram analisadas e comparadas com o grupo controle (sem tratamento) tanto para os neurônios corticais, como para os neurônios hipocampais. O objetivo do estudo foi: 1) avaliar, nessas culturas celulares, a atividade de diferentes quinases (PKA, CaMKII, AKT e GSK3beta), diferentes sítio de fosforilação da Tau (Ser, 199, 205, 214, 396, C-terminal e seis isoformas), a partir da inibição da PLA2 pelo lítio; 2) Investigar as vias de sinalização envolvidas na modulação do estado de fosforilação da proteína tau a partir da inibição da PLA2 em culturas primárias de neurônios; 3) avaliar, simultaneamente, a expressão de fatores neurotróficos (BDNF) e citocinas (GM-CSF, IL-1b, IL-2, IL-4, IL-5, IL6, IL-10, IL-12, IFN-y e TNF-alfa) mediante o tratamento de neurônios primários com lítio e 4) avaliar expressão gênica por microarray das culturas tratadas com diferentes doses, subterapêuticas e terapêutica, de cloreto de lítio. Nossos resultados sugerem uma dissociação de efeitos em neurônios corticais dos observados em neurônios hipocampais. O lítio aumentou a atividade enzimática da iPLA2 e da cPLA2, tanto em neurônios corticais como em neurônios hipocampais. A atividade da GSK3beta foi inibida pelo tratamento crônico com lítio em neurônios hipocampais e apresentou efeito contrário em neurônios corticais. Observamos comportamentos diferentes das diferentes proteínas analisadas em culturas de neurônios corticais e hipocampais, e não tivemos significância estatística para as alterações na proteína tau. O tratamento nas doses subterapêuticas aumentou a secreção de citocinas pró-inflamatórias tanto em neurônios corticais quanto em neurônios hipocampaisThe present study compared the effect of lithium chronic treatment with subtherapeutic doses (0.02mM and 0.2mM) and therapeutic dose (2mM) in primary cortical and hippocampal neurons cell culture. This samples were analyzed and compared with the control group (no treatment). The study\'s goal was: 1) to evaluate in these Cell Culture a different activity kinases (PKA, CaMKII, AKT and GSK3beta), different phosphorylation site of the Tau (199, 205, 214, 396, C-terminal and Six isoforms) and PLA2 inhibition; 2) To investigate how signaling pathways involved in modulation of tau phosphorylation from the inhibition of PLA2 in primary cultures of neurons; 3) analyze an expression of neurotrophic factors (BDNF) and cytokines (GM-CSF, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IFNy TNFalfa 4) to evaluate gene expression via microarray with different doses of lithium treatment. Our results suggest a dissociation effects on cortical and hippocampal neurons cell culture. Lithium increased the enzyme activity of iPLA2 and cPLA2, in both cortical and hippocampal neurons. The GSK3beta the activity was inhibited by chronic treatment with lithium in hippocampal neurons and presented contrary effect on cortical neurons. We observe not statistics significance on tau protein. The treatment at subtherapeutic and therapeutic doses increased the secretion of pro and anti-inflammatory cytokines both in cortical and hippocampal neurons
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Cheikh, Meriam. "Devenir respectable: une jeunesse populaire féminine au prisme de l'économie intime, Tanger - Maroc." Doctoral thesis, Universite Libre de Bruxelles, 2015. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209001.
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Turco, Lucia. "Tanja : processi mediterranei e pratiche di resistenza : un’etnografia situata e in traduzione delle lotte delle donne dei quartieri popolari." Thesis, Aix-Marseille, 2018. http://www.theses.fr/2018AIXM0145/document.
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La recherche proposée mène une analyse des processus de mondialisation qui intéressent la ville de Tanger et des conséquentes luttes de femmes des quartiers populaires contre les effets du développement néo-libéral sur le territoire. À partir d'une dimension internationale, liée spécifiquement aux discours sur la constitution de la macro-région méditerranéenne, j’insiste sur la manière dont les politiques de privatisation et d'accaparement des IDE Investissements Directs Étrangers ont produit des conséquences importantes surtout dans la région du Nord. Au nom de la politique de régionalisation et à la lumière du rôle central reconnu désormais à la géographie méditerranéenne, la région nord est le territoire où les plans méditerranéens se mettent en place: des nombreuses zones franches et industrielles ont vu le jour et par conséquent une forte migration des campagnes vers les villes a créé une urbanisation toujours croissante. La recherche ethnographique a été développée à Tanja, le principal centre urbain de la région nord, où une série de luttes populaires à grande participation féminine a eu lieu. Je les analyse en les contextualisant avec les projets de développement qui intéressent la zone. A l’aide d’une observation participante et d’une série d’interviews individuelles et de groupes, j’indique des parcours de réflexion autour de certains axes thématiques, tels que l'autorité, la protestation, la façon de traverser l’espace. La dernière partie consiste dans l’application de la méthode déconstructionniste sur un signifiant spécifique qui ressort, même si situé différemment, des récits des femmes interviewées: la maisonHere proposed un analysis of the development projects concerning the city of Tangier and the struggles of the women living in the popular zones.Starting from an international dimension, which is particularly related to the construction of the Mediterranean region, I underline how the privatization processes and the FDI Foreign Direct Investments grabbing, produced deep consequences especially in the Northern region of Morocco. Connecting to the regionalization process and the central role of the Mediterranean geography, the region is the territory for the implementation of Mediterranean projects: installation of industrial and free zones that produces the increase of the internal migration (from countryside to city) with the consequent progressive urbanization of the region.The ethnographic research took place in Tanja, the main urban centre of the North where different popular fights, with a predominant women’s participation, occur. The narration of these struggles is in a constant dialogue with insights on some specific development projects Some lines of thought around thematic aces like authority, protest and space crossing are identified through a methodology of participant observation and several semi-structured interviews with the women implicated in the struggles.The last part of the work consist in applying the deconstructionist method to a specific signifier: the home
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Piper, Eleanor Anne. "Chasing After the Tangle." PDXScholar, 2016. http://pdxscholar.library.pdx.edu/open_access_etds/3017.
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This is a collection of narrative nonfiction that spans forms: immersive journalism, quick character profiles, middling personal essays, and nostalgia in fragments, these works examine Sasquatch hunters, female mixed martial artists, absent fathers, Cuban punk rockers, and the gasps of an industry in decline.
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Taylor, Alexander John. "Analysis of quantised vortex tangle." Thesis, University of Bristol, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.683405.
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This thesis is an investigation of the tangled vortex lines that arise in the interference of complex waves in three dimensions; they are nodal lines of the intensity where both the real and imaginary components of the wavefield cancel out, and are singularities of the complex phase about which it sweeps out a quantised total change. We investigate the behaviour of this tangle as expressed in random degenerate eigenfunctions of the 3-torus, 3-sphere and quantum harmonic oscillator as models for wave chaos, in which many randomly weighted interfering waves produce a statistically characteristic vortex ensemble. The geometrical and topological nature of these vortex tangles is examined via large scale numerical simulations of random wave fields; local geometry is recovered with sufficient precision to confirm the connection to analytical random wave models, but we also recover the (high order) torsion that appears analytically inaccessible, and quantify the different length scales along which vortex lines decorrelate. From our simulations we recover statistics also on much larger scales, confirming a fractality of individual vortices consistent with random walks but also comparing and contrasting the scaling of the full vortex ensemble with other models of filamentary tangle. The nature of the tangling itself is also investigated, geometrically where possible but in particular topologically by testing directly whether vortex curves are knotted or linked with one another. We confirm that knots and links exist, but find their statistics greatly influenced by the nature of the random wave ensemble; vortices in the 3-torus are knotted far less than might be expected from their scales of geometrical de correlation, but in the 3-sphere and harmonic oscillator exhibit more common and more complex topology. We discuss how this result relates to the construction of each system, and finish with brief discussion of some selected topological observations.
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Ozawa, Makoto. "Tangle decompositions of knots and links /." Electronic version of summary, 1999. http://www.wul.waseda.ac.jp/gakui/gaiyo/2848.pdf.
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Avogadro, di Collobiano Simone. "Tangled Nature : a model on ecological evolution." Thesis, Imperial College London, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.271963.
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Ling, H. "Unravelling the tangled web of atypical parkinsonism." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1418946/.
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This thesis focuses on sporadic parkinsonian syndromes that are associated with neurofibrillary degeneration and the accumulation of abnormal tau protein in the brain. The classic clinical presentation of corticobasal degeneration is a specific constellation of cortical and extrapyramidal signs, collectively termed corticobasal syndrome. The evaluation of all the archival cases with corticobasal degeneration in the Queen Square Brain Bank for Neurological Disorders reveals the high frequency of other phenotypic presentations. The result indicates that corticobasal degeneration commonly presents with a clinical picture, closely resembling progressive supranuclear palsy (PSP) or Richardson’s syndrome. On the other hand, cases with typical PSP pathology may occasionally present with a corticobasal syndrome. A quantitative assessment of the severity of tau pathology in different brain regions of the two phenotypic presentations of PSP reveals topographical differences that are closely linked with their respective clinical features. The features of repetitive finger tapping and handwriting in patients with PSP and Parkinson’s disease are compared and a distinct abnormality is identified in PSP which may be useful in differentiating PSP-parkinsonism from Parkinson’s disease. Twelve cases clinically presenting with a levodopa-responsive parkinsonian syndrome and post-mortem findings of nigral degeneration and predominant tau inclusions, which could not be readily classified into any recognised clinicopathological entity are also studied.
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Berryman, Archer. "Pulling Tangled Strings: "The Puppeteer" and Other Stories." Thesis, University of North Texas, 2006. https://digital.library.unt.edu/ark:/67531/metadc5388/.
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Pulling Tangled Strings: "The Puppeteer" and Other Stories is a collection of stories with strong thematic and emotional connections that includes an opening preface describing the process used when writing the stories. Each of the stories is united by a main character that desperately wants to gain control of his environment. From a character acting out a classic revenge tale on his friend to a comatose teenager victimized by an ambiguous tragedy, these are characters who have been put into difficult life situations and need to feel like they are pulling the strings in their lives again. In all cases, however, the characters come to find that control does not come easily and that the motivations for their behavior are never clear cut, even to themselves.
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Chandrasekhar, Kartik. "Mechanical and microstructural behaviour of tangled metal wire devices." Thesis, University of Sheffield, 2016. http://etheses.whiterose.ac.uk/17182/.
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As the push towards the use of lighter and more efficient materials continues, energy dissipation from vibrating structures made from such materials is growing in importance. Viscoelastic materials have most often been employed to tackle vibration problems. In several applications, such as in the space and defence fields, the operating conditions usually do not allow for such solutions to be utilised. Tangled metal wire (TMW) devices offer an alternative damping strategy. Since the microstructure of such devices is made of metallic materials, they operate resiliently over a wide range of environments. The microstructure of a typical TMW device is made of metal wires that have been woven and compressed into an entangled state. Although they possess favourable properties, the manufacturing process makes the microstructure very complex, and the mechanical behaviour, as a result, tends to be unpredictable. The main theme of this thesis links the mechanical behaviour of TMW devices to their microstructural characteristics. A new algorithm is developed to study the microstructure of TMW devices from images obtained via microcomputed tomography (μ-CT) scanning. Following the application of compressive loads during the μ-CT scanning, it has been shown, for the first time, how the complex microstructural state evolves under different loading conditions. Parallel to this, displacement controlled experiments are performed on the TMW devices under quasi-static, low frequency, and high frequency loading conditions in an effort to ascertain the important phenomenological effects that dominate their response. Various analytical models are also explored and analysed with the aim of identifying an appropriate model for TMW devices. An analytical model, the frictional Zener model, is developed further to replicate the experimentally observed force-displacement hysteretic trends. The developed models, named the multi-chain frictional Zener models, include various additional terms to the basic model. Parameters are identified for the proposed models, and a model that gives acceptable accuracy with respect to experimentally observed hysteresis is found. This model is able to exhibit the spring-like nature of TMW devices, and it provides energy dissipation via classical Coulomb friction. The terms in the model are justified through analysis of the image processing results. Previous researchers have thus far not been able to fully justify the reasons why TMW devices behave the way they do since the microstructure has not been completely understood. The benefit of studying both the microstructural and mechanical properties of TMW devices in the manner outlined above is that a more holistic reasoning for observed behaviour is attained. The relatively simple proposed analytical model can be used to predict dynamic response when TMW devices are applied to real structures. As the confidence levels in the understanding of the TMW device microstructure and modelling aspects increase, more applications can take advantage of the favourable mechanical properties (especially in terms of energy dissipation) TMW devices showcase.
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Lauda, Aaron Dean. "Open-closed topological quantum field theory and tangle homology." Thesis, University of Cambridge, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.614322.
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MacKinnon, Rebeccah. "An equivalence between combinatorial tangle floer and contact categories." Diss., University of Iowa, 2019. https://ir.uiowa.edu/etd/6989.
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We prove an equivalence between the category underlying combinatorial tangle Floer homology and the contact category by building on the prior work of Lipshitz, Ozsváth, and Thurston and later Zhan. In his 2015 paper "Formal Contact Categories", Cooper establishes a relationship between the categories associated to oriented surfaces by Heegaard Floer theory and embedded contact theory. In this thesis, we examine a special case of his general argument to show an equivalence between the categories discussed by Petkova and Vértesi and those discussed by Tian. To do this, we construct two bimodules associated to the transformations between the underlying structure of combinatorial tangle Floer homology and the contact category. We take the tensor product of these bimodules and show that the product is equivalent to the identity, inducing an isomorphism between the categories of interest.
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Conci, Andrea. "BugBits: Making tangibles with children." Doctoral thesis, Università degli studi di Trento, 2018. https://hdl.handle.net/11572/369008.
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The thesis presents and discusses the processes that lead to the development of a tangible toolkit for supporting design workshops aimed at building tangible interfaces with children. The toolkit, called BugBits, was used to explore and instantiate participatory design workshops with children enabling them to be creative and develop new prototypes. BugBits was tested in three case studies with children of different ages. The first study was conducted in a modern art museum, where children aged between 13 and 15 years old (N=185) built personalised artefacts with the toolkit. The artefacts were then used to perform an augmented visit to some of the exhibition rooms of the museum. The second study (N=31) was conducted in a kindergarten with children between 3 and 6 years old. The toolkit was adopted to perform two educational exercises about colours characteristics. The third study (N=24) explored how the toolkit can be used to instantiate creative processes during participatory design workshops with children between 7 and 11 years old. During the studies, qualitative and quantitative data were collected and analysed.
The outcomes of the analysis show that the toolkit can be used with success to keep the children engaged (study 1, 2, 3) and obtain an active and effective participation (study 3) and allow them to build new and evolving TUI prototypes (study 3). By retrospectively reflecting on the process, the thesis presents the KPW process to guide and instantiate the design of generative tools for TUI design with children. The KPW process poses particular attention to the children roles, and how the technological choices affect the design.
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Conci, Andrea. "BugBits: Making tangibles with children." Doctoral thesis, University of Trento, 2018. http://eprints-phd.biblio.unitn.it/3439/1/Andrea_Conci_-_BugBits_Making_tangibles_with_children_-_Eprints.pdf.
Full textAbstract:
The thesis presents and discusses the processes that lead to the development of a tangible toolkit for supporting design workshops aimed at building tangible interfaces with children. The toolkit, called BugBits, was used to explore and instantiate participatory design workshops with children enabling them to be creative and develop new prototypes. BugBits was tested in three case studies with children of different ages. The first study was conducted in a modern art museum, where children aged between 13 and 15 years old (N=185) built personalised artefacts with the toolkit. The artefacts were then used to perform an augmented visit to some of the exhibition rooms of the museum. The second study (N=31) was conducted in a kindergarten with children between 3 and 6 years old. The toolkit was adopted to perform two educational exercises about colours characteristics. The third study (N=24) explored how the toolkit can be used to instantiate creative processes during participatory design workshops with children between 7 and 11 years old. During the studies, qualitative and quantitative data were collected and analysed.
The outcomes of the analysis show that the toolkit can be used with success to keep the children engaged (study 1, 2, 3) and obtain an active and effective participation (study 3) and allow them to build new and evolving TUI prototypes (study 3). By retrospectively reflecting on the process, the thesis presents the KPW process to guide and instantiate the design of generative tools for TUI design with children. The KPW process poses particular attention to the children roles, and how the technological choices affect the design.
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Ainsworth, Diann Elizabeth Smith. ""Strangely tangled threads" American women writers negotiating naturalism, 1850-1900 /." Fort Worth, Tex. : Texas Christian University, 2007. http://etd.tcu.edu/etdfiles/available/etd-12072007-113413/unrestricted/ainsworth.pdf.
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Valicenti, Elizabeth Anne. "The Tangled Web: How Nonprofit Board Members Experience Organizational Crisis." Antioch University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=antioch1337818367.
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