Dynamic characterization of cellulose nanofibrils in sheared and extended semi-dilute dispersions

New materials made through controlled assembly of dispersed cellulose nanofibrils (CNF) has the potential to develop into biobased competitors to some of the highest performing materials today. The performance of these new cellulose materials depends on how easily CNF alignment can be controlled with hydrodynamic forces, which are always in competition with a different process driving the system towards isotropy, called rotary diffusion. In this work, we present a flow-stop experiment using polarized optical microscopy (POM) to study the rotary diffusion of CNF dispersions in process relevant flows and concentrations. This is combined with small angle X-ray scattering (SAXS) experiments to analyze the true orientation distribution function (ODF) of the flowing fibrils. It is found that the rotary diffusion process of CNF occurs at multiple time scales, where the fastest scale seems to be dependent on the deformation history of the dispersion before the stop. At the same time, the hypothesis that rotary diffusion is dependent on the initial ODF does not hold as the same distribution can result in different diffusion time scales. The rotary diffusion is found to be faster in flows dominated by shear compared to pure extensional flows. Furthermore, the experimental setup can be used to quickly characterize the dynamic properties of flowing CNF and thus aid in determining the quality of the dispersion and its usability in material processes.Comment: 45 pages, 13 figure

Non-Hermitian Hamiltonians in field theory

This thesis is centred around the role of non-Hermitian Hamiltonians in Physics both at the quantum and classical levels. In our investigations of two-level models we demonstrate [1] the phenomenon of fast transitions developed in the PT -symmetric quantum brachistochrone problem may in fact be attributed to the non-Hermiticity of evolution operator used, rather than to its invariance under PT operation. Transition probabilities are calculated for Hamiltonians which explicitly violate PT -symmetry. When it comes to Hilbert spaces of infinite dimension, starting with non-Hermitian Hamiltonians expressed as linear and quadratic combinations of the generators of the su(1; 1) Lie algebra, we construct [2] Hermitian partners in the same similarity class. Alongside, metrics with respect to which the original Hamiltonians are Hermitian are also constructed, allowing to assign meaning to a large class of non-Hermitian Hamiltonians possessing real spectra. The finding of exact results to establish the physical acceptability of other non-Hermitian models may be pursued by other means, especially if the system of interest cannot be expressed in terms of Lie algebraic elements. We also employ [3] a representation of the canonical commutation relations for position and momentum operators in terms of real-valued functions and a noncommutative product rule of differential form. Besides exact solutions, we also compute in a perturbative fashion metrics and isospectral partners for systems of physical interest. Classically, our efforts were concentrated on integrable models presenting PT - symmetry. Because the latter can also establish the reality of energies in classical systems described by Hamiltonian functions, we search for new families of nonlinear differential equations for which the presence of hidden symmetries allows one to assemble exact solutions. We use [4] the Painleve test to check whether deformations of integrable systems preserve integrability. Moreover we compare [5] integrable deformed models, which are thus likely to possess soliton solutions, to a broader class of systems presenting compacton solutions. Finally we study [6] the pole structure of certain real valued nonlinear integrable systems and establish that they behave as interacting particles whose motion can be extended to the complex plane in a PT -symmetric way.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

CCR2 and CXCR4 regulate peripheral blood monocyte pharmacodynamics and link to efficacy in experimental autoimmune encephalomyelitis

<p>Abstract</p> <p>Background</p> <p>CCR2 plays a key role in regulating monocyte trafficking to sites of inflammation and therefore has been the focus of much interest as a target for inflammatory disease.</p> <p>Methods</p> <p>Here we examined the effects of CCR2 blockade with a potent small molecule antagonist to determine the pharmacodynamic consequences on the peripheral blood monocyte compartment in the context of acute and chronic inflammatory processes.</p> <p>Results</p> <p>We demonstrate that CCR2 antagonism <it>in vivo </it>led to a rapid decrease in the number of circulating Ly6C^himonocytes and that this decrease was largely due to the CXCR4-dependent sequestration of these cells in the bone marrow, providing pharmacological evidence for a mechanism by which monocyte dynamics are regulated <it>in vivo</it>. CCR2 antagonism led to an accumulation of circulating CCL2 and CCL7 levels in the blood, indicating a role for CCR2 in regulating the levels of its ligands under homeostatic conditions. Finally, we show that the pharmacodynamic changes due to CCR2 antagonism were apparent after chronic dosing in mouse experimental autoimmune encephalomyelitis, a model in which CCR2 blockade demonstrated a dramatic reduction in disease severity, manifest in a reduced accumulation of monocytes and other cells in the CNS.</p> <p>Conclusion</p> <p>CCR2 antagonism <it>in vivo </it>has tractable pharmacodynamic effects that can be used to align target engagement with biologic effects on disease activity.</p

A selective and potent CXCR3 antagonist SCH 546738 attenuates the development of autoimmune diseases and delays graft rejection

<p>Abstract</p> <p>Background</p> <p>The CXCR3 receptor and its three interferon-inducible ligands (CXCL9, CXCL10 and CXCL11) have been implicated as playing a central role in directing a Th1 inflammatory response. Recent studies strongly support that the CXCR3 receptor is a very attractive therapeutic target for treating autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis and psoriasis, and to prevent transplant rejection. We describe here the in vitro and in vivo pharmacological characterizations of a novel and potent small molecule CXCR3 antagonist, SCH 546738.</p> <p>Results</p> <p>In this study, we evaluated in vitro pharmacological properties of SCH 546738 by radioligand receptor binding and human activated T cell chemotaxis assays. In vivo efficacy of SCH 546738 was determined by mouse collagen-induced arthritis, rat and mouse experimental autoimmune encephalomyelitis, and rat cardiac transplantation models. We show that SCH 546738 binds to human CXCR3 with a high affinity of 0.4 nM. In addition, SCH 546738 displaces radiolabeled CXCL10 and CXCL11 from human CXCR3 with IC₅₀ranging from 0.8 to 2.2 nM in a non-competitive manner. SCH 546738 potently and specifically inhibits CXCR3-mediated chemotaxis in human activated T cells with IC₉₀about 10 nM. SCH 546738 attenuates the disease development in mouse collagen-induced arthritis model. SCH 546738 also significantly reduces disease severity in rat and mouse experimental autoimmune encephalomyelitis models. Furthermore, SCH 546738 alone achieves dose-dependent prolongation of rat cardiac allograft survival. Most significantly, SCH 546738 in combination with CsA supports permanent engraftment.</p> <p>Conclusions</p> <p>SCH 546738 is a novel, potent and non-competitive small molecule CXCR3 antagonist. It is efficacious in multiple preclinical disease models. These results demonstrate that therapy with CXCR3 antagonists may serve as a new strategy for treatment of autoimmune diseases, including rheumatoid arthritis and multiple sclerosis, and to prevent transplant rejection.</p