An NMR spectroscopy study of trimethylsilylmethyllilthium, TMSM-Li, indicates that TMSM-Li exists as two different aggregates in cyclopentane solution. Using previously reported colligative properties of TMSM-Li in different solutions in connection with new 13C and 6Li NMR data collected in this study, aggregation states were assigned as octamer and hexamer. Low temperature 13C and 6Li NMR peak intensities indicated an equilibrium exists between the two aggregates that shifts toward the octamer as the temperature decreases. ΔH was calculated to be 5.23 + 0.15 kcal/mol and ΔS was calculated to be 17.9 + 0.6 eu for the hexamer/octamer equilibrium system. Samples of TMSM-Li were mixed with TMSM-OH in attempts to form mixed alkyllithium/lithium alkoxide aggregates. 13C NMR data for these mixtures gave inconclusive results whether or not these compounds formed, which is different from other primary alkyllithium compounds studied in the past. A study of neopentyllithium, NpLi, indicates only one aggregate in solution with the aggregation state unknown using low temperature 13C NMR spectroscopy.

Abstract not available

Nonionic surfactants are commonly used to stabilize proteins during upstream and downstream processing and drug formulation. Surfactants stabilize the proteins through two major mechanisms: (i) their preferential location at nearby interfaces, in this way precluding protein adsorption; and/or (ii) their association with protein into "complexes" that prevent proteins from interacting with surfaces as well as each other. In general, both mechanisms must be at play for effective protein stabilization against aggregation and activity loss, but selection of surfactants for protein stabilization currently is not made with benefit of any quantitative, predictive information to ensure that this requirement is met. In certain circumstances the kinetics of surface tension depression (by surfactant) in protein-surfactant mixtures has been observed to be greater than that recorded for surfactant alone at the same concentration. We compared surface tension depression by poloxamer 188 (Pluronic�� F68), polysorbate 80 (PS 80), and polysorbate 20 (PS 20) in the presence and absence of lysozyme and recombinant protein, at different surfactant concentrations and temperatures. The kinetic results were interpreted with reference to a mechanism for surfactant adsorption governed by the formation of a rate-limiting structural intermediate (i.e., an "activated complex") comprised of surfactant aggregates and protein. The presence of lysozyme was seen to increase the rate of surfactant adsorption in relation to surfactant acting alone at the same concentrations for the polysorbates while less of an effect was seen for Pluronic�� F68. However, the addition of salt was observed to accelerate the surface tension depression of Pluronic�� F68 in the presence of lysozyme. The addition of a more hydrophobic, surface active protein (Amgen recombinant protein) in place of lysozyme resulted in greater enhancement of surfactant adsorption than that recorded in the presence of lysozyme. A simple thermodynamic analysis indicated the presence of protein caused a reduction in ���G for the surfactant adsorption process, with this reduction deriving entirely from a reduction in ���H. We suggest that protein accelerates the adsorption of these surfactants by disrupting their self associations, increasing the concentration of surfactant monomers near the interface. Based on these air-water tensiometry results, it is fair to expect that accelerated surfactant adsorption in the presence of protein (observed with PS 20 and PS 80) will occur with surfactants that stabilize protein mainly by their own adsorption at interfaces, and that the absence of accelerated surfactant adsorption (observed with F68) will be observed with surfactants that form stable surfactant-protein associations. Optical waveguide lightmode spectroscopy was used to test this expectation. Adsorption kinetics were recorded for surfactants (PS 20, PS 80, or F68) and protein (lysozyme or Amgen recombinant protein) at a hydrophilic solid (SiO���-TiO���) surface. Experiments were performed in sequential and competitive adsorption modes, enabling the adsorption kinetic patterns to be interpreted in a fashion revealing the dominant mode of surfactant-mediated stabilization of protein in each case. Kinetic results confirmed predictions based on our earlier quantitative analysis of protein effects on surface tension depression by surfactants. In particular, PS 20 and PS 80 are able to inhibit protein adsorption only by their preferential location at the interface, and not by formation of less surface active, protein-surfactant complexes. On the other hand, F68 is able to inhibit protein adsorption by formation of protein-surfactant complexes, and not by its preferential location at the interface. / Graduation date: 2013 / Access restricted to the OSU Community at author's request from Sept. 24, 2012 - Feb. 24, 2013.

Thesis (Ph. D.)--University of Alberta, 2010. / Title from pdf file main screen (viewed on July 17, 2010). A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy, [Department of] Mechanical Engineering, University of Alberta. Includes bibliographical references.

Thesis (Ph. D.)--University of Texas at Austin, 2008. / Vita. Includes bibliographical references.

Beta-Amyloid (1-40) (Aβ40) is an aggregation prone protein, which undergoes a nucleation-dependent aggregation process causing the pathological neurodegeneration by amyloid plaque formation implicated in Alzheimer’s disease. In this thesis, we investigated the effects of small molecule modulators extracted from the marine invertebrate Pseudopterogorgia elisabethae on the Aβ40 amyloidogenic process using in- vitro ThT fluorescence assay and atomic force microscopy. We also investigated the effects of neutral and anionic phospholipid liposomes on Aβ40 aggregation. Our results show that a marine natural product Pseudopterosin-A and its derivatives can suppress and modulate the Aβ40 aggregation process. Furthermore, our results demonstrate that a neutral phospholipid liposome inhibits Aβ40 fibril formation, whereas the anionic liposomes promote it. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2015 / FAU Electronic Theses and Dissertations Collection

In order to better predict the aggregation state of nanomaterials, the factors that influence aggregation must be understood. The combined effects of natural and engineered coatings have been shown to factor into nanoparticle aggregation behavior in preliminary research. In this study, aggregation behaviors of gold nanoparticles with two different engineered coatings were investigated in the presence of the monovalent electrolyte KCl and the divalent electrolyte CaCl���. Aggregation studies were conducted using dynamic light scattering to determine the relative stability of the NMs in environments of varying ionic strength in the absence and presence of Suwannee River Natural Organic Matter (SRNOM). Coatings which provided primarily electrostatic stabilization were found to adhere closely to DLVO theory, while coatings which provided steric stability inhibited aggregation over a wide range of ionic strengths for both electrolytes. The presence of SRNOM was found to provide some electrostatic stability in the presence of KCl, but appeared to form agglomerates with calcium ions, especially at higher SRNOM concentrations. / Graduation date: 2013

Suspension flows in varied settings and at different concentrations of particles are studied theoretically using various modeling techniques. Particulate suspension flows are dispersion of particles in a continuous medium and their properties are a consequence of the interplay among hydrodynamic, buoyancy, interparticle and Brownian forces. The applicability of continuum modeling techniques to suspension flows at different particle concentration was assessed by studying systems at different time and length scales. The first two studies involve the use of modeling techniques that are valid in systems where the forces between particles are negligible, which is the case in dilute suspension flows. In the first study, the growth and progradation of deltaic geologic bodies from the sedimentation of particles from dilute turbidity currents is modeled using the shallow water equations or vertically averaged equations of motions coupled with a particle conservation equation. The shallow water model provides a basis for extracting grain size and depositional history information from seismic data. Next, the Navier-Stokes equations of motion and the convection-diffusion equation are used to model suspension flow in a biomedical application involving the flow and reaction of drug laden nanovectors in arteries. Results from this study are then used prescribe the best design parameters for optimal nanovector uptake at the desired sites within an artery. The third study involves the use of macroscopic two phase models to describe concentrated suspension flows where interparticle hydrodynamic forces cannot be neglected. The isotropic form of both the diffusion-flux and the suspension balance models are solved for a buoyant bidisperse pressure-driven flow system. The model predictions are found to compare fairly well with experimental results obtained previously in our laboratory. Finally, the power of discrete type models in connecting macroscopic observations to structural details is demonstrated by studying a system of aggregating colloidal particles via Brownian dynamics. The results from the simulations match experimental shear rheology and also provide a structural explanation for the observed macroscopic behavior of aging. / text

Indiana University-Purdue University Indianapolis (IUPUI) / Intrinsically disordered proteins (IDPs) are flexible proteins without defined 3D structures. Studies show that IDPs are abundant in nature and actively involved in numerous biological processes. Two crucial subjects in the study of IDPs lie in analyzing IDPs’ functions and identifying them. We thus carried out three projects to better understand IDPs. In the 1st project, we propose a method that separates IDPs into different function groups. We used the approach of CH-CDF plot, which is based the combined use of two predictors and subclassifies proteins into 4 groups: structured, mixed, disordered, and rare. Studies show different structural biases for each group. The mixed class has more order-promoting residues and more ordered regions than the disordered class. In addition, the disordered class is highly active in mitosis-related processes among others. Meanwhile, the mixed class is highly associated with signaling pathways, where having both ordered and disordered regions could possibly be important. The 2nd project is about identifying if an unknown protein is entirely disordered. One of the earliest predictors for this purpose, the charge-hydropathy plot (C-H plot), exploited the charge and hydropathy features of the protein. Not only is this algorithm simple yet powerful, its input parameters, charge and hydropathy, are informative and readily interpretable. We found that using different hydropathy scales significantly affects the prediction accuracy. Therefore, we sought to identify a new hydropathy scale that optimizes the prediction. This new scale achieves an accuracy of 91%, a significant improvement over the original 79%. In our 3rd project, we developed a per-residue C-H IDP predictor, in which three hydropathy scales are optimized individually. This is to account for the amino acid composition differences in three regions of a protein sequence (N, C terminus and internal). We then combined them into a single per-residue predictor that achieves an accuracy of 74% for per-residue predictions for proteins containing long IDP regions.