subject:(aggregation)

University of Manchester

1. Ratanji, Kirsty. Investigating the immunogenicity of therapeutic proteins: protein aggregation and host cell protein impurities.

Degree: 2017, University of Manchester

URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:306714

► The development of anti-drug antibodies (ADA) against therapeutic proteins can impact upon drug safety and efficacy. This is a major challenge in the development of… (more)

▼ The development of anti-drug antibodies (ADA) against therapeutic proteins can impact upon drug safety and efficacy. This is a major challenge in the development of biotherapeutics. Various factors have the potential to contribute to protein immunogenicity and the production of ADA. Protein aggregation is one of these factors, though the mechanisms underlying aggregate immunogenicity are poorly understood. In this thesis the effect of protein aggregation on immunogenicity has been investigated.The thermal and/or mechanical stresses required in order to achieve subvisible aggregates of three test proteins were determined. Stressed preparations of proteins were characterised using a suite of biophysical techniques, including dynamic light scattering and circular dichroism. The immunogenic potential of subvisible aggregates of a humanised single chain variable fragment (scFv) and ovalbumin (OVA) was studied following intraperitoneal exposure in BALB/c strain mice. Monomeric proteins induced a T helper (Th) 2 dominant immune response, but when aggregated, the responses gained a Th1 phenotype, with a significant increase in the antigen-specific IgG2a antibody response. Cytokine profiles in supernatants taken from splenocyte-dendritic cell co-cultures were also consistent with aggregated preparations of OVA inducing a Th1-type response. Host cell protein (HCP) impurities can also contribute to immunogenicity. Mass spectrometry analysis of an scFv preparation identified the presence of the Escherichia coli (E.coli) heat shock protein DnaK, amongst other HCP, as an impurity. Protein preparations free from DnaK were spiked with recombinant E.coli DnaK to mimic the HCP impurity. The effect of DnaK on the immunogenicity of aggregated and monomeric scFv preparations was then investigated. BALB/c mice were immunised with monomeric and aggregated preparations, with and without E.coli DnaK at 0.1% by mass. Aggregation alone resulted in an enhanced IgG2a antibody response, and the presence of DnaK increased this further. Comparable investigations were also conducted using mouse albumin; here an increase in immunogenicity was observed with protein aggregation, and the presence of DnaK was found to increase the IgG2a response.Collectively, the evidence presented in this thesis shows that aggregation can impact upon the magnitude and character of induced immune responses, and that subvisible aggregation promotes a Th1 immune skewing. Additionally, E.coli HCP DnaK enhances protein aggregate immunogenicity, which indicates that heat shock proteins, as a class of HCP, could have an adjuvant-like effect on biotherapeutic aggregates. Advisors/Committee Members: KIMBER, IAN I, DEARMAN, REBECCA RJ, Derrick, Jeremy, Kimber, Ian, Dearman, Rebecca.

Subjects/Keywords: immunogenicity; aggregation

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APA (6^th Edition):

Ratanji, K. (2017). Investigating the immunogenicity of therapeutic proteins: protein aggregation and host cell protein impurities. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:306714

Chicago Manual of Style (16^th Edition):

Ratanji, Kirsty. “Investigating the immunogenicity of therapeutic proteins: protein aggregation and host cell protein impurities.” 2017. Doctoral Dissertation, University of Manchester. Accessed February 27, 2021. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:306714.

MLA Handbook (7^th Edition):

Ratanji, Kirsty. “Investigating the immunogenicity of therapeutic proteins: protein aggregation and host cell protein impurities.” 2017. Web. 27 Feb 2021.

Vancouver:

Ratanji K. Investigating the immunogenicity of therapeutic proteins: protein aggregation and host cell protein impurities. [Internet] [Doctoral dissertation]. University of Manchester; 2017. [cited 2021 Feb 27]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:306714.

Council of Science Editors:

Ratanji K. Investigating the immunogenicity of therapeutic proteins: protein aggregation and host cell protein impurities. [Doctoral Dissertation]. University of Manchester; 2017. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:306714

University of Waterloo

2. Primmer, Heather. Predicting and Measuring Molecular Mechanisms of Protein Aggregation.

Degree: 2011, University of Waterloo

URL: http://hdl.handle.net/10012/6178

► Protein aggregation is a hallmark of a number of neurodegenerative disorders including Alzheimer’s Disease, Huntington’s Disease, and Amyotrophic Lateral Sclerosis. Despite the common occurrence of… (more)

▼ Protein aggregation is a hallmark of a number of neurodegenerative disorders including Alzheimer’s Disease, Huntington’s Disease, and Amyotrophic Lateral Sclerosis. Despite the common occurrence of protein aggregation in disease, the fundamental mechanisms controlling the propensity of a protein to aggregate are not well understood. Over the past decade, one of the most significant advancements in the field of understanding protein aggregation has been the development of several aggregation prediction algorithms. In this study, two separate approaches were used to investigate the detailed molecular mechanisms of protein aggregation. First, a thorough investigation that compared nine protein aggregation prediction techniques was performed. Protein aggregation propensity calculations were performed on wild type and mutant sequences of three diverse proteins including Superoxide Dismutase (SOD), human Acylphosphatase (AcP), and the amyloid beta peptide (Aβ42). This study presents the first wide-scale comparison of such a large number of prediction algorithms, and additionally provides new information on the ability of the algorithms to successfully predict the experimentally observed aggregation of several mutations of diverse proteins. The algorithms were predominantly developed based on a set of known amyloid-forming proteins and peptides, however, are quite diverse in the way they were designed and the proteins on which they were tested. Interestingly, significant variation was observed when predicting the aggregation propensity of identical sequences by multiple techniques, indicating that the algorithms do not possess a consensus on the primary factors that govern aggregation. Further analyses compared predicted and observed aggregation data for several mutants of the test proteins. The aggregation prediction algorithms predominantly demonstrated poor to moderate correlations with observed aggregation, and the strongest correlations occurred in instances where the test data was used in the development of the algorithms. The general lack of ability of the algorithms to predict the aggregation patterns of more than one test protein suggests that aggregation may be a much more specific process that it is generally attributed to be in that there may be inherently different properties modulating the aggregation mechanisms of different proteins towards varying aggregate structures. The second component of this project was to experimentally examine the role of salt in influencing protein aggregation as a method to elucidate the specific molecular mechanisms controlling protein aggregation pathways. The ALS-causing SOD1 mutation, A4V, in both the oxidized and reduced apo form, was used as a model protein. The role of NaCl and Na2SO4 in mediating protein aggregation was studied using several techniques. While oxidized apo A4V showed very little evidence of aggregation even in the presence of salt, for reduced apo, aggregates readily formed and were promoted by the addition of salt. This finding correlated with the…

Subjects/Keywords: protein aggregation

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APA (6^th Edition):

Primmer, H. (2011). Predicting and Measuring Molecular Mechanisms of Protein Aggregation. (Thesis). University of Waterloo. Retrieved from http://hdl.handle.net/10012/6178

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Primmer, Heather. “Predicting and Measuring Molecular Mechanisms of Protein Aggregation.” 2011. Thesis, University of Waterloo. Accessed February 27, 2021. http://hdl.handle.net/10012/6178.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Primmer, Heather. “Predicting and Measuring Molecular Mechanisms of Protein Aggregation.” 2011. Web. 27 Feb 2021.

Vancouver:

Primmer H. Predicting and Measuring Molecular Mechanisms of Protein Aggregation. [Internet] [Thesis]. University of Waterloo; 2011. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10012/6178.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Primmer H. Predicting and Measuring Molecular Mechanisms of Protein Aggregation. [Thesis]. University of Waterloo; 2011. Available from: http://hdl.handle.net/10012/6178

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Rutgers University

3. Chaturbedi, Anik Kumar, 1989-. A combined computational and experimental study of the heteroaggregation of dissimilar adsorbent particles.

Degree: PhD, Chemical and Biochemical Engineering, 2019, Rutgers University

URL: https://rucore.libraries.rutgers.edu/rutgers-lib/60067/

► Heteroaggregation, the process of aggregation between dissimilar particles is becoming increasingly popular due to the versatile applicability of heteroaggregates. The specific requirements of these widespread… (more)

▼ Heteroaggregation, the process of aggregation between dissimilar particles is becoming increasingly popular due to the versatile applicability of heteroaggregates. The specific requirements of these widespread application areas require customized heteroaggregates with unique set of properties related mainly to the size and composition of these heteroaggregates. This has created an immense need for a developed understanding of the heteroaggregate process. However, research on heteroaggregates have been very limited, even fundamental questions pertinent to the mechanism of heteroaggregation process remain unanswered to date. The goal of this work is to study and understand the heteroaggregation process both at particle scale to answer some of these fundamental queries about heteroaggregate structure and composition and also use that knowledge to advance the development of process scale models of heteroaggregation. The first aim of this study is to develop a population balance model (PBM) for the second stage of the heteroaggregation process or the agglomeration stage to predict final heteroaggregate particle size distribution (PSD). The model is also used to study the effect of different parameters on the important forces in the system such as electrostatic, van der Waals and hydration force to understand factors that lead to a faster agglomeration dynamics. The model is validated by comparing with experimentally measured final heteroaggregate PSD. The second objective of this work is to develop a model for the first stage of the heteroaggregation process or the layering stage where smaller nanoparticles layer on a larger microparticle and affect its properties, thereby making it more susceptible to aggregation with other such particles in the second stage of heteroaggregation. The model results are compared with the experimental study of monoaggregate structure performed by scanning electron microscopic imaging of the same. This is essential for understanding factors that regulate and limit layering, and in turn affect the monoaggregate distribution and consequently heteroaggregate PSD and the presence of different heteroaggregate regimes. Furthermore, these two models are combined to develop an integrated model for both stages of the heteroaggregation process. The progress of the system towards different heteroaggregation regimes have also been simulated and validated experimentally by studying the final heteroaggregate PSD. The third aim of this study is to investigate the adsorption characteristics of the heteroaggregates for the adsorption of oppositely charged heavy metal ions from single ion as well as mixed ion systems which represent real industrial wastewater more accurately than commonly studied single ion systems. The adsorption capacities of the heteroaggregates from three different regimes are also compared with the adsorption characteristics of the individual components of the heteroaggregates to see if the heteroaggregates offer an advantage over the individual adsorbents. The bio-friendly nature,… Advisors/Committee Members: Ramachandran, Rohit (chair), Shapley, Nina (co-chair), Chiew, Yee (internal member), Hara, Masanori (internal member), Reinfelder, John (outside member), School of Graduate Studies.

Subjects/Keywords: Aggregation (Chemistry)

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APA (6^th Edition):

Chaturbedi, Anik Kumar, 1. (2019). A combined computational and experimental study of the heteroaggregation of dissimilar adsorbent particles. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/60067/

Chicago Manual of Style (16^th Edition):

Chaturbedi, Anik Kumar, 1989-. “A combined computational and experimental study of the heteroaggregation of dissimilar adsorbent particles.” 2019. Doctoral Dissertation, Rutgers University. Accessed February 27, 2021. https://rucore.libraries.rutgers.edu/rutgers-lib/60067/.

MLA Handbook (7^th Edition):

Chaturbedi, Anik Kumar, 1989-. “A combined computational and experimental study of the heteroaggregation of dissimilar adsorbent particles.” 2019. Web. 27 Feb 2021.

Vancouver:

Chaturbedi, Anik Kumar 1. A combined computational and experimental study of the heteroaggregation of dissimilar adsorbent particles. [Internet] [Doctoral dissertation]. Rutgers University; 2019. [cited 2021 Feb 27]. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/60067/.

Council of Science Editors:

Chaturbedi, Anik Kumar 1. A combined computational and experimental study of the heteroaggregation of dissimilar adsorbent particles. [Doctoral Dissertation]. Rutgers University; 2019. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/60067/

Rutgers University

4. Yang, Xue, 1991-. Investigation of protein - protein interactions underlying alpha-synuclein aggregation in Parkinson's diseases.

Degree: PhD, Chemistry and Chemical Biology, 2020, Rutgers University

URL: https://rucore.libraries.rutgers.edu/rutgers-lib/62585/

►

Alpha-synuclein (αSynuclein) accumulation and aggregation is related to many neurodegenerative diseases like Alzheimer's diseases, Parkinson’s diseases, and dementia with Lewy bodies. However, the mechanism of… (more)

▼

Alpha-synuclein (αSynuclein) accumulation and aggregation is related to many neurodegenerative diseases like Alzheimer's diseases, Parkinson’s diseases, and dementia with Lewy bodies. However, the mechanism of αSynuclein aggregation and the relationship between aggregation pathways and toxicity are still unclear. Beta-synuclein (βSynuclein) is a homologue protein of αSynuclein with high sequence similarity but plays a different role in neurodegenerative diseases. βSynuclein has shown anti-Parkinson capacity in mouse models. In this work, we used βSynuclein as a comparison to answer why αSynuclein fibrils are good templates for seeding aggregation and what kind of interactions promote aggregate formation or inhibition. The work in this thesis explores structure, toxicity, dynamic and seeding aggregation capacity of different αSynuclein oligomers and fibrils which provide critical information for therapeutic targets and designs. By characterizing and comparing αSynuclein, βSynuclein and α/β co-incubated fibrils, we suggest that the stability and dynamics of the fibrils play an important role in controlling the fibril seeding aggregation ability. However, both αSynuclein and βSynuclein fibrils show similar cellular toxicity which suggest that seeding monomer aggregation is not the only contribution for fibril toxicity. Using solution NMR, we show that the initial step for fibril seeding is through interactions at the first 40 residues of the N-terminus. The interactions between αSynuclein stable oligomers and monomers are primarily located at the first 12 residues which results in inhibiting fibril seeding aggregation processes through competing interactions. Coupling these facts together suggests that peptides or small molecular targets that interact with the N-terminus of αSynuclein may be a good approach to inhibit αSynuclein seeding processes and increase the dynamics of fibril packing interfaces can be novel strategies to reduce amyloid toxicity.

Advisors/Committee Members: Baum, Jean (chair), Khare, Sagar (internal member), Nieuwkoop, Andrew (internal member), Mouradian, Maral (outside member), School of Graduate Studies.

Subjects/Keywords: Aggregation; Synucleins

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APA (6^th Edition):

Yang, Xue, 1. (2020). Investigation of protein - protein interactions underlying alpha-synuclein aggregation in Parkinson's diseases. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/62585/

Chicago Manual of Style (16^th Edition):

Yang, Xue, 1991-. “Investigation of protein - protein interactions underlying alpha-synuclein aggregation in Parkinson's diseases.” 2020. Doctoral Dissertation, Rutgers University. Accessed February 27, 2021. https://rucore.libraries.rutgers.edu/rutgers-lib/62585/.

MLA Handbook (7^th Edition):

Yang, Xue, 1991-. “Investigation of protein - protein interactions underlying alpha-synuclein aggregation in Parkinson's diseases.” 2020. Web. 27 Feb 2021.

Vancouver:

Yang, Xue 1. Investigation of protein - protein interactions underlying alpha-synuclein aggregation in Parkinson's diseases. [Internet] [Doctoral dissertation]. Rutgers University; 2020. [cited 2021 Feb 27]. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/62585/.

Council of Science Editors:

Yang, Xue 1. Investigation of protein - protein interactions underlying alpha-synuclein aggregation in Parkinson's diseases. [Doctoral Dissertation]. Rutgers University; 2020. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/62585/

University of Alberta

5. Derakhshesh, Marzie. Asphaltene aggregation and fouling behavior.

Degree: PhD, Department of Chemical and Materials Engineering, 2012, University of Alberta

URL: https://era.library.ualberta.ca/files/cqr46r0958

► This thesis explored the properties of asphaltene nano-aggregates in crude oil and toluene based solutions and fouling at process furnace temperatures, and the links between… (more)

▼ This thesis explored the properties of asphaltene nano-aggregates in crude oil and toluene based solutions and fouling at process furnace temperatures, and the links between these two phenomena. The link between stability of asphaltenes at ambient conditions and fouling at the conditions of a delayed coker furnace, at over 450 ̊C, was examined by blending crude oil with an aliphatic diluent in different ratios. The stability of the blends were measured using a S-value analyzer, then fouling rates were measured on electrically heated stainless steel 316 wires in an autoclave reactor. The less stable the blend, the greater the rate and extent of fouling. The most severe fouling occurred with the unstable asphaltenes. SEM imaging of the foulant illustrates very different textures, with the structure becoming more porous with lower stability. Under cross-polarized light, the coke shows the presence of mesophase in the foulant layer. These data suggest a correlation between the fouling rate at high temperature furnace conditions and the stability index of the crude oil. Three organic polysulfides were introduced to the crude oil to examine their effect on fouling. The polysulfides are able to reduce coking and carbon monoxide generation in steam crackers. The fouling results demonstrated that polysulfide with more sulfur content increased the amount of corrosion-fouling of the wire. Various additives, solvents, ultrasound, and heat were employed to attempt to completely disaggregate the asphaltene nano-aggregates in solution at room temperature. The primary analytical technique used to monitor the nano- aggregation state of the asphaltenes in solution was the UV-visible spectroscopy. The results indicate that stronger solvents, such as pyridine and quinoline, combined with ionic liquids yield a slight reduction in the apparent absorbance at longer wavelengths, indicative of a decrease in the nano-aggregate size although the magnitude of the decrease is not significant. Analysis of the spectra of the whole asphaltene samples in toluene indicates that the absorbance of visible light with wavelengths > 600 nm follows a λ-4 dependence. This functional dependence is consistent with Rayleigh scattering. Rayleigh scattering provides strong evidence that the apparent absorption of visible light by asphaltenes from 600-800 nm is not a molecular absorption phenomenon but rather a scattering mechanism. Rayleigh scattering equations were combined with experimental visible spectra to estimate the average nanoaggregate sizes, which were in a very good agreement with the sizes reported in the literature. The occlusion of two polynuclear aromatic hydrocarbons (PAHs) (pyrene and phenanthrene) in asphaltene precipitates was tested by adding PAHs to the asphaltene in toluene solutions, precipitating by n-pentane and determining the amount of PAHs in precipitates using simulated distillation instrument. Pyrene and phenanthrene, which are normally soluble in the toluene-n-pentane solutions, were detected in the asphaltene precipitates at…

Subjects/Keywords: fouling; Asphaltene; aggregation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Derakhshesh, M. (2012). Asphaltene aggregation and fouling behavior. (Doctoral Dissertation). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/cqr46r0958

Chicago Manual of Style (16^th Edition):

Derakhshesh, Marzie. “Asphaltene aggregation and fouling behavior.” 2012. Doctoral Dissertation, University of Alberta. Accessed February 27, 2021. https://era.library.ualberta.ca/files/cqr46r0958.

MLA Handbook (7^th Edition):

Derakhshesh, Marzie. “Asphaltene aggregation and fouling behavior.” 2012. Web. 27 Feb 2021.

Vancouver:

Derakhshesh M. Asphaltene aggregation and fouling behavior. [Internet] [Doctoral dissertation]. University of Alberta; 2012. [cited 2021 Feb 27]. Available from: https://era.library.ualberta.ca/files/cqr46r0958.

Council of Science Editors:

Derakhshesh M. Asphaltene aggregation and fouling behavior. [Doctoral Dissertation]. University of Alberta; 2012. Available from: https://era.library.ualberta.ca/files/cqr46r0958

Cornell University

6. Hoepker, Alexander. Aggregation Dynamics Of Lithium Diisopropylamide And Their Mechanistic Influence On Reactivity.

Degree: PhD, Chemistry and Chemical Biology, 2011, Cornell University

URL: http://hdl.handle.net/1813/29114

► Lithium diisopropylamide (LDA) is the premier base in organic chemistry ever since its development in 1950 by Hammel and Levine. In a comprehensive survey of… (more)

▼ Lithium diisopropylamide (LDA) is the premier base in organic chemistry ever since its development in 1950 by Hammel and Levine. In a comprehensive survey of reagents in approximately 500 natural product syntheses, LDA emerged at the top attesting to its wide range of synthetic applications and efficacy. Significant efforts to the understanding of its complex coordination chemistry and affiliated mode of reactivity has led to a review by Collum that painted a seemingly coherent and general picture of LDA-mediated reactions. This mechanistic view, however, was gleaned under conditions in which LDA aggregate equilibria proceeded very quickly compared to the rate of the reaction. The kinetics of LDA aggregation, therefore, were inconsequential and hidden to the investigator. While shifting the focus to more reactive substrates that required a reduction in temperature to -78 °C to maintain convenient time scales for monitoring reaction rates, something odd happened. Instead of conventional first-order substrate decays that had been observed for almost twenty years, we began to observe nonstandard curvatures with evidence of substrate-independent rates, autocatalysis and lithium salt catalysis. The mechanistic intricacy was eventually traced to one common culprit: the rate of LDA aggregation at -78 °C in tetrahydrofuran (THF) had become rate-limiting with the rate of substrate reaction now being post-rate-limiting. The work described herein presents three experimental accounts that peer into the mechanism of three LDA-aggregation limited reactions: LDA-mediated ortholithiations of fluoroand trifluoromethyl arenes and the 1,4-addition to unsaturated esters. Although the studies are internally consistent, a chaotic mechanistic picture emerged that appeared to lack coherency. A theoretical treatise of LDA aggregation concludes this work in an attempt to comprehend the source of this complexity and garner a more general understanding. Dozens of reactive forms of LDA emerged as part of a potential energy surface that began to explain our experimental findings. Despite significant advances, we have only scratched the surface of the mechanistic diversity of LDA aggregation. The kinetic tools and knowledge, however, are now in place to peer ever deeper into this mechanistic extravaganza. Advisors/Committee Members: Collum, David B (chair), Chen, Peng (committee member), Coates, Geoffrey (committee member).

Subjects/Keywords: lda; Aggregation; Kinetics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hoepker, A. (2011). Aggregation Dynamics Of Lithium Diisopropylamide And Their Mechanistic Influence On Reactivity. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/29114

Chicago Manual of Style (16^th Edition):

Hoepker, Alexander. “Aggregation Dynamics Of Lithium Diisopropylamide And Their Mechanistic Influence On Reactivity.” 2011. Doctoral Dissertation, Cornell University. Accessed February 27, 2021. http://hdl.handle.net/1813/29114.

MLA Handbook (7^th Edition):

Hoepker, Alexander. “Aggregation Dynamics Of Lithium Diisopropylamide And Their Mechanistic Influence On Reactivity.” 2011. Web. 27 Feb 2021.

Vancouver:

Hoepker A. Aggregation Dynamics Of Lithium Diisopropylamide And Their Mechanistic Influence On Reactivity. [Internet] [Doctoral dissertation]. Cornell University; 2011. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/1813/29114.

Council of Science Editors:

Hoepker A. Aggregation Dynamics Of Lithium Diisopropylamide And Their Mechanistic Influence On Reactivity. [Doctoral Dissertation]. Cornell University; 2011. Available from: http://hdl.handle.net/1813/29114

University of Miami

7. Tseng, LeinWeih Andrew. Ubiquitylation of Neuronal Pentraxin with Chromo Domain by the E3 Ubiquitin Ligase Mayven/KLHL2 and Effects on Aggresome Formation and Neuronal Cytotoxicity.

Degree: PhD, Molecular and Cellular Pharmacology (Medicine), 2010, University of Miami

URL: https://scholarlyrepository.miami.edu/oa_dissertations/662

► Neuronal pentraxin with chromo domain (NPCD) belongs to a family of neuronally-expressed pentraxin proteins thought to be involved in synaptic refinement and plasticity. One… (more)

▼ Neuronal pentraxin with chromo domain (NPCD) belongs to a family of neuronally-expressed pentraxin proteins thought to be involved in synaptic refinement and plasticity. One isoform of Npcd, neuronal pentraxin receptor (NPR), is a type-II transmembrane protein responsible for the clustering of related neuronal pentraxins 1 and 2. However, recently identified cytosolic NPCD isoforms with no known function were discovered through their interaction with the intracellular domain of a receptor protein tyrosine phosphatase PTPRO. PTPRO is a signaling molecule known to be involved in the development of the nervous system. Additionally, upregulated expression of neuronal pentraxins has been implicated in neuronal cytotoxicity and associated with neurodegenerative diseases. Here, we demonstrate that a novel cytosolic NPCD isoform interacts with the BTB-Kelch protein Mayven/KLHL2. This interaction was identified through a yeast two-hybrid screen using the C-terminal pentraxin domain region of NPCD and confirmed through mammalian cell colocalization and co-immunoprecipitation studies. Domain truncation analysis suggests that the kelch domains of Mayven/KLHL2 are responsible for this interaction with NPCD. We also show that Mayven/KLHL2 is capable of interacting with Cullin 3, an integral protein in the Cullin-RING ubiquitin ligase complex. An in-vivo ubiquitylation assay demonstrates that overexpression of Mayven/KLHL2 increases NPCD ubiquitylation, and suggests a novel E3 ubiquitin ligase function of Mayven/KLHL2 with NPCD as its substrate. Furthermore, we observed an increased propensity of overexpressed NPCD to form aggresomes with coexpression of Mayven/KLHL2. As the formation of aggresomes is often associated with protein aggregation and deposition diseases, including a multitude of neurodegenerative diseases, we tested NPCD overexpression and the effects of Mayven/KLHL2 coexpression on neuronal cytotoxicity and apoptosis. Overexpressed NPCD in hippocampal neuron cultures resulted in increased cytotoxicity and apoptosis, further exacerbated by Mayven/KLHL2 coexpression. Our findings report an interaction between NPCD and Mayven/KLHL2, demonstrate a novel role of Mayven/KLHL2 as an E3 ubiquitin ligase, and explore a possible intersection between the ubiquitin-proteasome degradation pathway, neuronal pentraxins, and neurodegenerative disease. Advisors/Committee Members: Fulvia Verde, Sandra Lemmon, Abigail Hackam, John Bixby, Nagi Ayad - Outside Committee Member.

Subjects/Keywords: Protein Aggregation; Neurodegeneration

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APA (6^th Edition):

Tseng, L. A. (2010). Ubiquitylation of Neuronal Pentraxin with Chromo Domain by the E3 Ubiquitin Ligase Mayven/KLHL2 and Effects on Aggresome Formation and Neuronal Cytotoxicity. (Doctoral Dissertation). University of Miami. Retrieved from https://scholarlyrepository.miami.edu/oa_dissertations/662

Chicago Manual of Style (16^th Edition):

Tseng, LeinWeih Andrew. “Ubiquitylation of Neuronal Pentraxin with Chromo Domain by the E3 Ubiquitin Ligase Mayven/KLHL2 and Effects on Aggresome Formation and Neuronal Cytotoxicity.” 2010. Doctoral Dissertation, University of Miami. Accessed February 27, 2021. https://scholarlyrepository.miami.edu/oa_dissertations/662.

MLA Handbook (7^th Edition):

Tseng, LeinWeih Andrew. “Ubiquitylation of Neuronal Pentraxin with Chromo Domain by the E3 Ubiquitin Ligase Mayven/KLHL2 and Effects on Aggresome Formation and Neuronal Cytotoxicity.” 2010. Web. 27 Feb 2021.

Vancouver:

Tseng LA. Ubiquitylation of Neuronal Pentraxin with Chromo Domain by the E3 Ubiquitin Ligase Mayven/KLHL2 and Effects on Aggresome Formation and Neuronal Cytotoxicity. [Internet] [Doctoral dissertation]. University of Miami; 2010. [cited 2021 Feb 27]. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/662.

Council of Science Editors:

Tseng LA. Ubiquitylation of Neuronal Pentraxin with Chromo Domain by the E3 Ubiquitin Ligase Mayven/KLHL2 and Effects on Aggresome Formation and Neuronal Cytotoxicity. [Doctoral Dissertation]. University of Miami; 2010. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/662

University of Miami

8. Tseng, LeinWeih Andrew. Ubiquitylation of Neuronal Pentraxin with Chromo Domain by the E3 Ubiquitin Ligase Mayven/KLHL2 and Effects on Aggresome Formation and Neuronal Cytotoxicity.

Degree: PhD, Molecular and Cellular Pharmacology (Medicine), 2010, University of Miami

URL: https://scholarlyrepository.miami.edu/oa_dissertations/928

► Neuronal pentraxin with chromo domain (NPCD) belongs to a family of neuronally-expressed pentraxin proteins thought to be involved in synaptic refinement and plasticity. One… (more)

▼ Neuronal pentraxin with chromo domain (NPCD) belongs to a family of neuronally-expressed pentraxin proteins thought to be involved in synaptic refinement and plasticity. One isoform of Npcd, neuronal pentraxin receptor (NPR), is a type-II transmembrane protein responsible for the clustering of related neuronal pentraxins 1 and 2. However, recently identified cytosolic NPCD isoforms with no known function were discovered through their interaction with the intracellular domain of a receptor protein tyrosine phosphatase PTPRO. PTPRO is a signaling molecule known to be involved in the development of the nervous system. Additionally, upregulated expression of neuronal pentraxins has been implicated in neuronal cytotoxicity and associated with neurodegenerative diseases. Here, we demonstrate that a novel cytosolic NPCD isoform interacts with the BTB-Kelch protein Mayven/KLHL2. This interaction was identified through a yeast two-hybrid screen using the C-terminal pentraxin domain region of NPCD and confirmed through mammalian cell colocalization and co-immunoprecipitation studies. Domain truncation analysis suggests that the kelch domains of Mayven/KLHL2 are responsible for this interaction with NPCD. We also show that Mayven/KLHL2 is capable of interacting with Cullin 3, an integral protein in the Cullin-RING ubiquitin ligase complex. An in-vivo ubiquitylation assay demonstrates that overexpression of Mayven/KLHL2 increases NPCD ubiquitylation, and suggests a novel E3 ubiquitin ligase function of Mayven/KLHL2 with NPCD as its substrate. Furthermore, we observed an increased propensity of overexpressed NPCD to form aggresomes with coexpression of Mayven/KLHL2. As the formation of aggresomes is often associated with protein aggregation and deposition diseases, including a multitude of neurodegenerative diseases, we tested NPCD overexpression and the effects of Mayven/KLHL2 coexpression on neuronal cytotoxicity and apoptosis. Overexpressed NPCD in hippocampal neuron cultures resulted in increased cytotoxicity and apoptosis, further exacerbated by Mayven/KLHL2 coexpression. Our findings report an interaction between NPCD and Mayven/KLHL2, demonstrate a novel role of Mayven/KLHL2 as an E3 ubiquitin ligase, and explore a possible intersection between the ubiquitin-proteasome degradation pathway, neuronal pentraxins, and neurodegenerative disease. Advisors/Committee Members: Fulvia Verde, Sandra Lemmon, Abigail Hackam, John Bixby, Nagi Ayad.

Subjects/Keywords: Protein Aggregation; Neurodegeneration

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APA (6^th Edition):

Tseng, L. A. (2010). Ubiquitylation of Neuronal Pentraxin with Chromo Domain by the E3 Ubiquitin Ligase Mayven/KLHL2 and Effects on Aggresome Formation and Neuronal Cytotoxicity. (Doctoral Dissertation). University of Miami. Retrieved from https://scholarlyrepository.miami.edu/oa_dissertations/928

Chicago Manual of Style (16^th Edition):

Tseng, LeinWeih Andrew. “Ubiquitylation of Neuronal Pentraxin with Chromo Domain by the E3 Ubiquitin Ligase Mayven/KLHL2 and Effects on Aggresome Formation and Neuronal Cytotoxicity.” 2010. Doctoral Dissertation, University of Miami. Accessed February 27, 2021. https://scholarlyrepository.miami.edu/oa_dissertations/928.

MLA Handbook (7^th Edition):

Tseng, LeinWeih Andrew. “Ubiquitylation of Neuronal Pentraxin with Chromo Domain by the E3 Ubiquitin Ligase Mayven/KLHL2 and Effects on Aggresome Formation and Neuronal Cytotoxicity.” 2010. Web. 27 Feb 2021.

Vancouver:

Tseng LA. Ubiquitylation of Neuronal Pentraxin with Chromo Domain by the E3 Ubiquitin Ligase Mayven/KLHL2 and Effects on Aggresome Formation and Neuronal Cytotoxicity. [Internet] [Doctoral dissertation]. University of Miami; 2010. [cited 2021 Feb 27]. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/928.

Council of Science Editors:

Tseng LA. Ubiquitylation of Neuronal Pentraxin with Chromo Domain by the E3 Ubiquitin Ligase Mayven/KLHL2 and Effects on Aggresome Formation and Neuronal Cytotoxicity. [Doctoral Dissertation]. University of Miami; 2010. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/928

Université de Neuchâtel

9. Stigliano, Egidio. The role of palmitoylation in the secretoy pathway of plants.

Degree: 2011, Université de Neuchâtel

URL: http://doc.rero.ch/record/234529

► This study aimed to study an important eukaryotic post-translational modification, the S-palmitoylation. Until now, there was no study of palmitoylation in plant cell biology. In… (more)

▼ This study aimed to study an important eukaryotic post-translational modification, the S-palmitoylation. Until now, there was no study of palmitoylation in plant cell biology. In the first part of this study, we wanted to study the palmitoylation of the vacuolar receptor AtRMR1, as predicted <i>in silico</i>. We used a very innovative technique, the Biotin Switch Assay, which does not use radioactive palmitate, is much less time-consuming as it is possible to obtain results after three to four day. Another advantage for cell biology is that it allows the characterization of entire palmitoyl-proteomes. Yeast and neuronal palmitoyl-proteomes have indeed been recently characterized. The study of RMR1’s palmitoylation revealed the first palmitoylated plant transmembrane protein. The palmitoylation of a small fraction of RMR1 at a higher molecular weight deserves further discussion. In the second part of this thesis, I addressed the more general role of palmitoylation in the secretory pathway through the use of a potent palmitoylation inhibitor: 2BP. This study showed a specific action of the drug in TGN/post-TGN compartments. The drug affected the structural maintenance of macrovesicles of secretion. The macrovesicles of secretion have recently been characterized by cryofixation and by electron tomography. They are structures reminiscent of a bunch of grapes, where each grape is a secretory vesicle. They are associated with the building with TGN-rich secretory vesicles with a diameter of few tens of nanometres. These vesicles are particularly visible in tissues with a high growth rate, such as pollen tubes. 2BP drastically changed the state of aggregation of macrovesicles of secretion. In an imaged way, each grape was released and a diffuse fluorescence was observed. Palmitoylation is therefore important in the formation or stability of this important secretory structure. A possible extension of this work would be the isolation of palmitoylated proteins involved in this stabilization. In addition, palmitoylated Rabs were detected for the first time in a plant. The three plant Rabs for which I detected the effect of 2BP are located in post-Golgi compartments. In a last part of the thesis, I decided to investigate the route of secretion of GFP-Chi, a vacuolar markerwidely used in the lab that can be followed along the route of secretion. Apparent contradictions have been reported: a vacuolar sorting of this marker by the Golgi-TGN-PVC pathway or an independent-COPII trafficking that can bypass the classic route. Unexpectedly, when GFP-Chi was co-expressed with NtSar1H74L (a dominant-negative mutant blocking the ER-Golgi trafficking by preventing the formation of COPII vesicles), the reporter reached the vacuole. This suggests that the alternative pathway bypassing the Golgi can take place. I also detected the presence of a possible GFP-Chi dimer associated with the membrane fraction upon ultracentrifugation. The nature of this dimer of a soluble protein remains to be investigated although several cases of… Advisors/Committee Members: Jean-Marc (Dir.).

Subjects/Keywords: GFP-Chi aggregation

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APA (6^th Edition):

Stigliano, E. (2011). The role of palmitoylation in the secretoy pathway of plants. (Thesis). Université de Neuchâtel. Retrieved from http://doc.rero.ch/record/234529

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Stigliano, Egidio. “The role of palmitoylation in the secretoy pathway of plants.” 2011. Thesis, Université de Neuchâtel. Accessed February 27, 2021. http://doc.rero.ch/record/234529.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Stigliano, Egidio. “The role of palmitoylation in the secretoy pathway of plants.” 2011. Web. 27 Feb 2021.

Vancouver:

Stigliano E. The role of palmitoylation in the secretoy pathway of plants. [Internet] [Thesis]. Université de Neuchâtel; 2011. [cited 2021 Feb 27]. Available from: http://doc.rero.ch/record/234529.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Stigliano E. The role of palmitoylation in the secretoy pathway of plants. [Thesis]. Université de Neuchâtel; 2011. Available from: http://doc.rero.ch/record/234529

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Rice University

10. Cross, Daniel Mishael. Forecast Aggregation and Binned Sequential Testing in a Streaming Environment.

Degree: PhD, Engineering, 2017, Rice University

URL: http://hdl.handle.net/1911/105520

► This thesis report covers two separate projects. The sequential probability ratio test is a statistical test of one simple hypothesis against another. Oftentimes a parametric… (more)

▼ This thesis report covers two separate projects. The sequential probability ratio test is a statistical test of one simple hypothesis against another. Oftentimes a parametric form is assumed for the underlying density or (discrete) probability function, and the two hypotheses are specified by two different values of the parameter. In this case the sequential probability ratio test consists of taking observations sequentially and after each observation comparing the updated likelihood ratio to two constants that are chosen to specify type I and type II error probabilities. When the likelihood ratio crosses one of the constants the corresponding density to that constant is chosen to be the true density. For more closely mixed proposed densities the expected number of steps to decision may be large, but generally is less than a fixed n design with the same type I and II errors. In this situation data compression could be a necessity in order to reduce data storage requirements. In other situations, the data may arrive or be transformed into bins. In this paper we explore the effects of binning sequential data in two cases: (1) the exact binned (histogram) of densities is known; and (2) finite sample approximations of the exact histogram densities are known. We show the effects of binning in both cases on the expected number of steps to decision, and type I and type II error. Optimal binning parameter choices for common densities as well as formulae for general densities are also given. The Good Judgment Team led by psychologists P. Tetlock and B. Mellers of the University of Pennsylvania was the most successful of five research projects sponsored through 2015 by IARPA to develop improved group forecast aggregation algorithms. Each team had at least ten algorithms under continuous development and evaluation over the four year project. The mean Brier score was used to rank the algorithms on approximately 130 questions concerning categorical geopolitical events each year. An algorithm would return aggregate probabilities for each question based on the prob- abilities provided per question by thousands of individuals, who had been recruited by the Good Judgment Team. This paper summarizes the theorized basis and implementation of one of the two most accurate algorithms at the conclusion of the Good Judgment Project. The algorithm incorporated a number of pre- and post-processing steps, and relied upon a minimum distance robust regression method called L2E; see Scott (2001). The algorithm was just edged out by a variation of logistic regression, which has been described elsewhere; see Mellers et al. (2014) and GJP (2015a). Work since the official conclusion of the project has led to an even smaller gap. Advisors/Committee Members: Scott, David W (advisor).

Subjects/Keywords: Forecast Aggregation; Binning

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Cross, D. M. (2017). Forecast Aggregation and Binned Sequential Testing in a Streaming Environment. (Doctoral Dissertation). Rice University. Retrieved from http://hdl.handle.net/1911/105520

Chicago Manual of Style (16^th Edition):

Cross, Daniel Mishael. “Forecast Aggregation and Binned Sequential Testing in a Streaming Environment.” 2017. Doctoral Dissertation, Rice University. Accessed February 27, 2021. http://hdl.handle.net/1911/105520.

MLA Handbook (7^th Edition):

Cross, Daniel Mishael. “Forecast Aggregation and Binned Sequential Testing in a Streaming Environment.” 2017. Web. 27 Feb 2021.

Vancouver:

Cross DM. Forecast Aggregation and Binned Sequential Testing in a Streaming Environment. [Internet] [Doctoral dissertation]. Rice University; 2017. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/1911/105520.

Council of Science Editors:

Cross DM. Forecast Aggregation and Binned Sequential Testing in a Streaming Environment. [Doctoral Dissertation]. Rice University; 2017. Available from: http://hdl.handle.net/1911/105520

University of Ontario Institute of Technology

11. Frawley, Eryn. Study of a 2 dimensional aggregation model with non-linear adaptations.

Degree: 2018, University of Ontario Institute of Technology

URL: http://hdl.handle.net/10155/943

► In this paper we will explore the impacts on collective animal motion of adding non-linearity to the animals??? turning rate in a 2-dimensional model of… (more)

Subjects/Keywords: Aggregation; PDE; Symmetry

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APA (6^th Edition):

Frawley, E. (2018). Study of a 2 dimensional aggregation model with non-linear adaptations. (Thesis). University of Ontario Institute of Technology. Retrieved from http://hdl.handle.net/10155/943

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Frawley, Eryn. “Study of a 2 dimensional aggregation model with non-linear adaptations.” 2018. Thesis, University of Ontario Institute of Technology. Accessed February 27, 2021. http://hdl.handle.net/10155/943.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Frawley, Eryn. “Study of a 2 dimensional aggregation model with non-linear adaptations.” 2018. Web. 27 Feb 2021.

Vancouver:

Frawley E. Study of a 2 dimensional aggregation model with non-linear adaptations. [Internet] [Thesis]. University of Ontario Institute of Technology; 2018. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10155/943.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Frawley E. Study of a 2 dimensional aggregation model with non-linear adaptations. [Thesis]. University of Ontario Institute of Technology; 2018. Available from: http://hdl.handle.net/10155/943

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Waterloo

12. Trainor, Kyle. Inclusion Body Formation by Mutants of the Tenth Human Fibronectin Type III Domain.

Degree: 2015, University of Waterloo

URL: http://hdl.handle.net/10012/9239

► Inclusion bodies (IBs) are intracellular, insoluble protein aggregates, commonly observed when a protein of interest is expressed at high concentrations in a bacterial cell-based expression… (more)

▼ Inclusion bodies (IBs) are intracellular, insoluble protein aggregates, commonly observed when a protein of interest is expressed at high concentrations in a bacterial cell-based expression system. The molecular determinants of IB formation are poorly understood, and are of both fundamental and biotechnological significance. The stability, folding, and structure of the tenth human fibronectin type III domain (10Fn3) have been studied previously, making it an attractive model system to investigate IB formation. A library of 10Fn3 mutants was provided by Bristol-Myers Squibb; 31 of these mutants were expressed in Escherichia coli and analyzed. The percentage of the expressed protein found within IBs was quantified at different expression time points using densitometric analysis of soluble and inclusion body (insoluble) cell lysate fractions separated by centrifugation and subjected to polyacrylamide gel electrophoresis. Although most of these mutants differ from each other in only 3 amino acid positions, all found within a single flexible loop of the protein, the extent of IB formation varies greatly. This data set was used to test the performance of a variety of amino acid sequence-based protein aggregation prediction methods. Several of these methods produced predictions that correlate moderately well with the IB formation data (R2 > 0.6), suggesting that while the intrinsic aggregation propensity of sequence segments strongly influences IB formation, other factors are also relevant. We hypothesized that improved predictions might be made possible by the consideration of additional structural context, i.e. aggregation-prone sequence segment exposure. Thermodynamic stabilities determined using differential scanning calorimetry correlate poorly with IB formation; all of the mutants are sufficiently stable that no significant fraction of protein is likely to be denatured at equilibrium. To describe the variable structure of the flexible loop in which the mutant sequences differ, ensembles of homology models were constructed. IB formation was found to correlate with the ensemble average energy scores of the homology models. The ensemble average scores may capture subtle shifts in the energetic bias toward native structure that restricts the exposure of aggregation-prone sequence segments. A linear combination of sequence-based aggregation predictions and ensemble average homology model scores correlates much better with IB formation (R2 > 0.8) than either parameter does individually.

Subjects/Keywords: protein aggregation inclusion

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APA (6^th Edition):

Trainor, K. (2015). Inclusion Body Formation by Mutants of the Tenth Human Fibronectin Type III Domain. (Thesis). University of Waterloo. Retrieved from http://hdl.handle.net/10012/9239

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Trainor, Kyle. “Inclusion Body Formation by Mutants of the Tenth Human Fibronectin Type III Domain.” 2015. Thesis, University of Waterloo. Accessed February 27, 2021. http://hdl.handle.net/10012/9239.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Trainor, Kyle. “Inclusion Body Formation by Mutants of the Tenth Human Fibronectin Type III Domain.” 2015. Web. 27 Feb 2021.

Vancouver:

Trainor K. Inclusion Body Formation by Mutants of the Tenth Human Fibronectin Type III Domain. [Internet] [Thesis]. University of Waterloo; 2015. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10012/9239.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Trainor K. Inclusion Body Formation by Mutants of the Tenth Human Fibronectin Type III Domain. [Thesis]. University of Waterloo; 2015. Available from: http://hdl.handle.net/10012/9239

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

13. Pace, Samantha. EVALUATING NOVEL ANALYTICAL TECHNIQUES TO ASSESS THE INITIAL STEPS OF PROTEIN AGGREGATION USING VARIOUS ANTIBODY SOLUTIONS.

Degree: PhD, Pharmaceutical Chemistry, 2018, University of Kansas

URL: http://hdl.handle.net/1808/27830

► Antibody-based therapeutics continue to be a fast growing field in pharmaceutics due to their increased selectivity for a specific target over small molecule drugs. Antibody… (more)

▼ Antibody-based therapeutics continue to be a fast growing field in pharmaceutics due to their increased selectivity for a specific target over small molecule drugs. Antibody solutions are often formulated at high protein concentrations in order to achieve low injection volumes, especially for subcutaneous administration, which can cause many challenging problems when it comes to stabilization. The instability of antibodies can often lead to aggregation which can occur during many parts of the manufacturing process including purification, fill-finish, shipping and storage. Aggregation of antibodies can cause many problems such as not injecting the proper dose, due to a decrease in the protein’s concentration, or causing immunogenic responses that may affect the safety or efficacy of the drug potentially causing harm to patients. Therefore, the aggregation pathway(s) of antibody drug candidates need to be characterized in great detail and well understood before they reach the market. Currently, several common analytical techniques are being used to distinguish the amount and size of aggregation impurities produced when an antibody undergoes accelerated stresses during formulation development. However, more novel techniques are needed to get a better, more in-depth understanding of the types of aggregates formed along of the aggregation pathway. The development of novel techniques to screen antibody stability and aggregation propensities can not only elucidate degradation mechanisms that proteins undergo throughout the lifetime of the drug, it can also allow us to better understand effective ways to increase the shelf-life and maintain product safety. In this study, various monoclonal antibodies (mAb) and bispecific antibodies (biAb) were examined under varying stress conditions and their physical stability monitored using conventional and novel techniques. New techniques examined include a high throughput GroEL-based BLI (Biolayer interferometry) assay that helps identify less stable antibodies, formulations (excipients, pH values), and storage conditions (temperatures) by being able to detect pre-aggregate species forming prior to more established techniques show the formation of larger sized aggregates (methods such as size exclusion chromatography and micro-flow digital imaging). Another novel technique examined in these studies is the use of hydrogen-deuterium exchange mass spectrometry, which is used to identify problematic portions of the antibody molecule, by monitoring changes in local flexibility or rigidity, when exposed to different excipients and pH levels. Finally, the use of Langmuir trough to examine interfacial and intermolecular interaction properties of various antibodies and formulation conditions was evaluated. Understanding antibody molecules tendencies to drive to the air-water interface or have intermolecular interactions can predict physical instability problems throughout the purification process and during long term storage conditions. This type of aggregation risk assessment during early… Advisors/Committee Members: Volkin, David B (advisor), Middaugh, C. Russell (cmtemember), Hageman, Michael (cmtemember), Siahaan, Teruna (cmtemember), Ritcher, Mark (cmtemember).

Subjects/Keywords: Pharmaceutical sciences; Aggregation

10 more images…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Pace, S. (2018). EVALUATING NOVEL ANALYTICAL TECHNIQUES TO ASSESS THE INITIAL STEPS OF PROTEIN AGGREGATION USING VARIOUS ANTIBODY SOLUTIONS. (Doctoral Dissertation). University of Kansas. Retrieved from http://hdl.handle.net/1808/27830

Chicago Manual of Style (16^th Edition):

Pace, Samantha. “EVALUATING NOVEL ANALYTICAL TECHNIQUES TO ASSESS THE INITIAL STEPS OF PROTEIN AGGREGATION USING VARIOUS ANTIBODY SOLUTIONS.” 2018. Doctoral Dissertation, University of Kansas. Accessed February 27, 2021. http://hdl.handle.net/1808/27830.

MLA Handbook (7^th Edition):

Pace, Samantha. “EVALUATING NOVEL ANALYTICAL TECHNIQUES TO ASSESS THE INITIAL STEPS OF PROTEIN AGGREGATION USING VARIOUS ANTIBODY SOLUTIONS.” 2018. Web. 27 Feb 2021.

Vancouver:

Pace S. EVALUATING NOVEL ANALYTICAL TECHNIQUES TO ASSESS THE INITIAL STEPS OF PROTEIN AGGREGATION USING VARIOUS ANTIBODY SOLUTIONS. [Internet] [Doctoral dissertation]. University of Kansas; 2018. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/1808/27830.

Council of Science Editors:

Pace S. EVALUATING NOVEL ANALYTICAL TECHNIQUES TO ASSESS THE INITIAL STEPS OF PROTEIN AGGREGATION USING VARIOUS ANTIBODY SOLUTIONS. [Doctoral Dissertation]. University of Kansas; 2018. Available from: http://hdl.handle.net/1808/27830

University of Manchester

14. Gilburt, James. A study of folded, denatured and aggregated states during the refolding of inclusion body proteins.

Degree: 2016, University of Manchester

URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:295840

► The need to high quality therapeutic proteins has grown significantly in the past 30 years. Recombinant proteins are often produced from vectors inserted into E.… (more)

▼ The need to high quality therapeutic proteins has grown significantly in the past 30 years. Recombinant proteins are often produced from vectors inserted into E. coli cell lines for large scale production. However, over-expression of the protein within the cell can lead to the formation of large, insoluble aggregates known as inclusion bodies. Native monomer protein can be isolated from inclusion bodies through a refolding process. This entails disruption of the aggregate structure with high concentrations of denaturant and renaturation in native-promoting solution. Our work characterises protein-protein interactions and aggregation between partially unfolded proteins during the refolding process. The protein-protein interactions are characterized in terms of the osmotic second virial coefficient (B22). A positive value indicates repulsive interactions while a negative value indicates attractive interactions. Measurements are carried out for lysozyme, ribonuclease A and preproinsulin as a function of pH, ionic strength and denaturant concentration, alongside a range of known refolding excipients.Past studies (Ho and Middelberg, 2004; Ho et al., 2003) have shown a link between higher B22 values in denaturant solutions and reduced aggregation during refolding. Our experiments have focused on the effects of urea and GdmHCl upon protein-protein interactions, alongside how ionic strength and refolding additives influence interactions between partially-folded states. At low ionic strength, solutions of urea increase net repulsive interactions compared to GdmHCl solutions through an attenuation of short-range attractive interactions. Electrostatic repulsive interactions are screened in solutions of GdmHCl due to the increased ionic strength of the solution; however short-range attractive interactions are also attenuated in a similar fashion to urea solutions. Protein-protein interactions in low and high concentration denaturant solutions have been shown to be highly sensitive to ionic strength and refolding experiments have shown that this correlates with increased aggregation during refolding. The solubilising additive Arg HCl has been shown to reduce short-range attraction between proteins in urea solutions, while the folding-promotor additives sucrose and hexylene glycol have been shown to have a more complex effect on protein-protein interactions in urea solutions dependent on denaturant concentration.Within the wider context of the field of protein aggregation and refolding, the work conducted here will contribute towards the understanding of how denaturants and solutes influence attractive protein-protein interactions and aggregation behaviour between unfolded or partially folded proteins. Advisors/Committee Members: DERRICK, JEREMY JP, Curtis, Robin, Derrick, Jeremy.

Subjects/Keywords: Protein refolding; Aggregation

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APA (6^th Edition):

Gilburt, J. (2016). A study of folded, denatured and aggregated states during the refolding of inclusion body proteins. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:295840

Chicago Manual of Style (16^th Edition):

Gilburt, James. “A study of folded, denatured and aggregated states during the refolding of inclusion body proteins.” 2016. Doctoral Dissertation, University of Manchester. Accessed February 27, 2021. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:295840.

MLA Handbook (7^th Edition):

Gilburt, James. “A study of folded, denatured and aggregated states during the refolding of inclusion body proteins.” 2016. Web. 27 Feb 2021.

Vancouver:

Gilburt J. A study of folded, denatured and aggregated states during the refolding of inclusion body proteins. [Internet] [Doctoral dissertation]. University of Manchester; 2016. [cited 2021 Feb 27]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:295840.

Council of Science Editors:

Gilburt J. A study of folded, denatured and aggregated states during the refolding of inclusion body proteins. [Doctoral Dissertation]. University of Manchester; 2016. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:295840

University of Texas – Austin

15. Mand, Michael Rodgers. Mechanisms and consequences of ATM activation.

Degree: PhD, Cellular and Molecular Biology, 2015, University of Texas – Austin

URL: http://hdl.handle.net/2152/44484

► Mutations in the ataxia telangiectasia mutated (ATM) gene cause the disease ataxia-telangiectasia (A-T). Patients with this disease have multiple symptoms, including the eponymous ataxia and… (more)

▼ Mutations in the ataxia telangiectasia mutated (ATM) gene cause the disease ataxia-telangiectasia (A-T). Patients with this disease have multiple symptoms, including the eponymous ataxia and telangiectasia as well as immunodeficiency, radiation sensitivity, and increased cancer rates. The ATM protein is a kinase and is activated by multiple types of stress to affect many cellular processes. At sites of DNA double-strand breaks (DSBs), ATM is activated by the protein complex Mre11/Rad50/Nbs1 (MRN). As part of this complex, Rad50 binds and hydrolyzes ATP and causes large conformational changes in the complex. However, the importance of this enzymatic activity in the activation of ATM has been unknown. Here I show ATP binding by Rad50 is required for ATM activation while ATP hydrolysis is dispensable. ATM is also activated in the presence of oxidative stress. Separation-of-function mutations for the activation of ATM by DSBs and oxidative stress have been characterized in vitro. Here, the effects of expressing wild-type ATM or ATM with these different separation-of-function mutations in an ATM-deficient lymphoblast cell line have been characterized. Analysis of the proteomes of these cells and a control cell line revealed that non-functional ATM resulted in the loss of a large group of proteins by mass spectrometry. The levels of these proteins were similar in the cells, but in the presence of non-functional ATM they showed increased levels of aggregation. Thus my results suggest ATM may function to prevent aggregation in these conditions. Notably neurodegeneration is often associated with aggregation. In the phosphoproteomes of cells expressing the various ATM constructs, the parental cell line and cells with ATM unable to be activated by oxidative stress had lower levels of phosphopeptides predicted to be phosphorylated by CK2. This decrease in CK2 activity was also associated with increased aggregation, specifically a subunit of CK2 known as CK2β. This work provides insights into the mechanism of ATM activation by MRN and the potential involvement of ATM in the prevention of protein aggregation. Advisors/Committee Members: Paull, Tanya T. (advisor), Dalby, Kevin (committee member), Huibregtse, Jon (committee member), Marcotte, Edward (committee member), Miller, Kyle (committee member).

Subjects/Keywords: ATM; CK2; Aggregation

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APA (6^th Edition):

Mand, M. R. (2015). Mechanisms and consequences of ATM activation. (Doctoral Dissertation). University of Texas – Austin. Retrieved from http://hdl.handle.net/2152/44484

Chicago Manual of Style (16^th Edition):

Mand, Michael Rodgers. “Mechanisms and consequences of ATM activation.” 2015. Doctoral Dissertation, University of Texas – Austin. Accessed February 27, 2021. http://hdl.handle.net/2152/44484.

MLA Handbook (7^th Edition):

Mand, Michael Rodgers. “Mechanisms and consequences of ATM activation.” 2015. Web. 27 Feb 2021.

Vancouver:

Mand MR. Mechanisms and consequences of ATM activation. [Internet] [Doctoral dissertation]. University of Texas – Austin; 2015. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/2152/44484.

Council of Science Editors:

Mand MR. Mechanisms and consequences of ATM activation. [Doctoral Dissertation]. University of Texas – Austin; 2015. Available from: http://hdl.handle.net/2152/44484

University of Manchester

16. Ratanji, Kirsty. Investigating the immunogenicity of therapeutic proteins : protein aggregation and host cell protein impurities.

Degree: PhD, 2017, University of Manchester

URL: https://www.research.manchester.ac.uk/portal/en/theses/investigating-the-immunogenicity-of-therapeutic-proteins-protein-aggregation-and-host-cell-protein-impurities(fda43dd8-2c1e-492b-abd9-e010774d2219).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764545

► The development of anti-drug antibodies (ADA) against therapeutic proteins can impact upon drug safety and efficacy. This is a major challenge in the development of… (more)

▼ The development of anti-drug antibodies (ADA) against therapeutic proteins can impact upon drug safety and efficacy. This is a major challenge in the development of biotherapeutics. Various factors have the potential to contribute to protein immunogenicity and the production of ADA. Protein aggregation is one of these factors, though the mechanisms underlying aggregate immunogenicity are poorly understood. In this thesis the effect of protein aggregation on immunogenicity has been investigated. The thermal and/or mechanical stresses required in order to achieve subvisible aggregates of three test proteins were determined. Stressed preparations of proteins were characterised using a suite of biophysical techniques, including dynamic light scattering and circular dichroism. The immunogenic potential of subvisible aggregates of a humanised single chain variable fragment (scFv) and ovalbumin (OVA) was studied following intraperitoneal exposure in BALB/c strain mice. Monomeric proteins induced a T helper (Th) 2 dominant immune response, but when aggregated, the responses gained a Th1 phenotype, with a significant increase in the antigen-specific IgG2a antibody response. Cytokine profiles in supernatants taken from splenocyte-dendritic cell co-cultures were also consistent with aggregated preparations of OVA inducing a Th1-type response. Host cell protein (HCP) impurities can also contribute to immunogenicity. Mass spectrometry analysis of an scFv preparation identified the presence of the Escherichia coli (E.coli) heat shock protein DnaK, amongst other HCP, as an impurity. Protein preparations free from DnaK were spiked with recombinant E.coli DnaK to mimic the HCP impurity. The effect of DnaK on the immunogenicity of aggregated and monomeric scFv preparations was then investigated. BALB/c mice were immunised with monomeric and aggregated preparations, with and without E.coli DnaK at 0.1% by mass. Aggregation alone resulted in an enhanced IgG2a antibody response, and the presence of DnaK increased this further. Comparable investigations were also conducted using mouse albumin; here an increase in immunogenicity was observed with protein aggregation, and the presence of DnaK was found to increase the IgG2a response. Collectively, the evidence presented in this thesis shows that aggregation can impact upon the magnitude and character of induced immune responses, and that subvisible aggregation promotes a Th1 immune skewing. Additionally, E.coli HCP DnaK enhances protein aggregate immunogenicity, which indicates that heat shock proteins, as a class of HCP, could have an adjuvant-like effect on biotherapeutic aggregates.

Subjects/Keywords: 616.07; aggregation; immunogenicity

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APA (6^th Edition):

Ratanji, K. (2017). Investigating the immunogenicity of therapeutic proteins : protein aggregation and host cell protein impurities. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/investigating-the-immunogenicity-of-therapeutic-proteins-protein-aggregation-and-host-cell-protein-impurities(fda43dd8-2c1e-492b-abd9-e010774d2219).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764545

Chicago Manual of Style (16^th Edition):

Ratanji, Kirsty. “Investigating the immunogenicity of therapeutic proteins : protein aggregation and host cell protein impurities.” 2017. Doctoral Dissertation, University of Manchester. Accessed February 27, 2021. https://www.research.manchester.ac.uk/portal/en/theses/investigating-the-immunogenicity-of-therapeutic-proteins-protein-aggregation-and-host-cell-protein-impurities(fda43dd8-2c1e-492b-abd9-e010774d2219).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764545.

MLA Handbook (7^th Edition):

Ratanji, Kirsty. “Investigating the immunogenicity of therapeutic proteins : protein aggregation and host cell protein impurities.” 2017. Web. 27 Feb 2021.

Vancouver:

Ratanji K. Investigating the immunogenicity of therapeutic proteins : protein aggregation and host cell protein impurities. [Internet] [Doctoral dissertation]. University of Manchester; 2017. [cited 2021 Feb 27]. Available from: https://www.research.manchester.ac.uk/portal/en/theses/investigating-the-immunogenicity-of-therapeutic-proteins-protein-aggregation-and-host-cell-protein-impurities(fda43dd8-2c1e-492b-abd9-e010774d2219).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764545.

Council of Science Editors:

Ratanji K. Investigating the immunogenicity of therapeutic proteins : protein aggregation and host cell protein impurities. [Doctoral Dissertation]. University of Manchester; 2017. Available from: https://www.research.manchester.ac.uk/portal/en/theses/investigating-the-immunogenicity-of-therapeutic-proteins-protein-aggregation-and-host-cell-protein-impurities(fda43dd8-2c1e-492b-abd9-e010774d2219).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764545

NSYSU

17. Zhuang, Yi-Xing. Effect of deposition rate of host material N,Nâ-dicarbazolyl-3,5-benzene(mCP) in phosphorescent organic light-emitting diodes.

Degree: Master, Electro-Optical Engineering, 2012, NSYSU

URL: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0813112-170622

► Phosphorescent organic light-emitting diodes (PhOLED) have attracted a lot of attention in these years.Blue PhOLED is especially important because of short lifetime and low optoelectronic… (more)

Subjects/Keywords: Phosphorescence; mCP; Deposition rate; Aggregation

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APA (6^th Edition):

Zhuang, Y. (2012). Effect of deposition rate of host material N,Nâ-dicarbazolyl-3,5-benzene(mCP) in phosphorescent organic light-emitting diodes. (Thesis). NSYSU. Retrieved from http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0813112-170622

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Zhuang, Yi-Xing. “Effect of deposition rate of host material N,Nâ-dicarbazolyl-3,5-benzene(mCP) in phosphorescent organic light-emitting diodes.” 2012. Thesis, NSYSU. Accessed February 27, 2021. http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0813112-170622.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Zhuang, Yi-Xing. “Effect of deposition rate of host material N,Nâ-dicarbazolyl-3,5-benzene(mCP) in phosphorescent organic light-emitting diodes.” 2012. Web. 27 Feb 2021.

Vancouver:

Zhuang Y. Effect of deposition rate of host material N,Nâ-dicarbazolyl-3,5-benzene(mCP) in phosphorescent organic light-emitting diodes. [Internet] [Thesis]. NSYSU; 2012. [cited 2021 Feb 27]. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0813112-170622.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Zhuang Y. Effect of deposition rate of host material N,Nâ-dicarbazolyl-3,5-benzene(mCP) in phosphorescent organic light-emitting diodes. [Thesis]. NSYSU; 2012. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0813112-170622

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Ruhr Universität Bochum

18. Bornemann, Katrin Agnes Maria. Hemmung der Thrombozytenaggregation durch Metamizol, Ibuprofen, Paracetamol und Valdecoxib/Parecoxib unter Steady-State- Bedingungen.

Degree: 2009, Ruhr Universität Bochum

URL: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-26247

► Thrombozytenaggregationshemmende Effekte von NSAID sind bekannt. Welchen Einfluß hat die wiederholte Gabe von Metamizol auf die Thrombozytenfunktion und Aggregation? Die randomisierte, prospektive Studie vergleicht den… (more)

Subjects/Keywords: Analgetikum; Thrombozyt; Blutung; Blutgerinnung; Aggregation

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APA (6^th Edition):

Bornemann, K. A. M. (2009). Hemmung der Thrombozytenaggregation durch Metamizol, Ibuprofen, Paracetamol und Valdecoxib/Parecoxib unter Steady-State- Bedingungen. (Thesis). Ruhr Universität Bochum. Retrieved from http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-26247

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Bornemann, Katrin Agnes Maria. “Hemmung der Thrombozytenaggregation durch Metamizol, Ibuprofen, Paracetamol und Valdecoxib/Parecoxib unter Steady-State- Bedingungen.” 2009. Thesis, Ruhr Universität Bochum. Accessed February 27, 2021. http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-26247.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Bornemann, Katrin Agnes Maria. “Hemmung der Thrombozytenaggregation durch Metamizol, Ibuprofen, Paracetamol und Valdecoxib/Parecoxib unter Steady-State- Bedingungen.” 2009. Web. 27 Feb 2021.

Vancouver:

Bornemann KAM. Hemmung der Thrombozytenaggregation durch Metamizol, Ibuprofen, Paracetamol und Valdecoxib/Parecoxib unter Steady-State- Bedingungen. [Internet] [Thesis]. Ruhr Universität Bochum; 2009. [cited 2021 Feb 27]. Available from: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-26247.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bornemann KAM. Hemmung der Thrombozytenaggregation durch Metamizol, Ibuprofen, Paracetamol und Valdecoxib/Parecoxib unter Steady-State- Bedingungen. [Thesis]. Ruhr Universität Bochum; 2009. Available from: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-26247

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Ruhr Universität Bochum

19. Endres, Torsten. Untersuchung der Aggregation kleiner Aromaten in Heliumtröpfchen mittels Stark-Feld-IR-Spektroskopie.

Degree: 2013, Ruhr Universität Bochum

URL: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-37851

► In dieser Arbeit wurde die Aggregation kleiner Aromaten im Heliumtröpfchen mittels Stark-Feld-IR-Spektroskopie und ab- initio-Simulationen untersucht. Die aufgenommenen IR-Spektren von Benzol-Dimer zeigen, dass ausschließlich eine… (more)

Subjects/Keywords: Helium; Infrarotspektroskopie; Aggregation; Benzol; Pyridin

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APA (6^th Edition):

Endres, T. (2013). Untersuchung der Aggregation kleiner Aromaten in Heliumtröpfchen mittels Stark-Feld-IR-Spektroskopie. (Thesis). Ruhr Universität Bochum. Retrieved from http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-37851

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Endres, Torsten. “Untersuchung der Aggregation kleiner Aromaten in Heliumtröpfchen mittels Stark-Feld-IR-Spektroskopie.” 2013. Thesis, Ruhr Universität Bochum. Accessed February 27, 2021. http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-37851.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Endres, Torsten. “Untersuchung der Aggregation kleiner Aromaten in Heliumtröpfchen mittels Stark-Feld-IR-Spektroskopie.” 2013. Web. 27 Feb 2021.

Vancouver:

Endres T. Untersuchung der Aggregation kleiner Aromaten in Heliumtröpfchen mittels Stark-Feld-IR-Spektroskopie. [Internet] [Thesis]. Ruhr Universität Bochum; 2013. [cited 2021 Feb 27]. Available from: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-37851.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Endres T. Untersuchung der Aggregation kleiner Aromaten in Heliumtröpfchen mittels Stark-Feld-IR-Spektroskopie. [Thesis]. Ruhr Universität Bochum; 2013. Available from: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-37851

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Oregon State University

20. Bolsinger, Travis Samuel Sebastian. Human platelet adhesion to heparinized silica surfaces.

Degree: MS, Chemical Engineering, 2008, Oregon State University

URL: http://hdl.handle.net/1957/9292

► Heparin was modified and immobilized to surface-activated silica surfaces using two different reaction schemes. End-aminated heparin was reacted with 2-iminothiolane to produce free thiol groups… (more)

Subjects/Keywords: Heparin; Blood platelets – Aggregation

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APA (6^th Edition):

Bolsinger, T. S. S. (2008). Human platelet adhesion to heparinized silica surfaces. (Masters Thesis). Oregon State University. Retrieved from http://hdl.handle.net/1957/9292

Chicago Manual of Style (16^th Edition):

Bolsinger, Travis Samuel Sebastian. “Human platelet adhesion to heparinized silica surfaces.” 2008. Masters Thesis, Oregon State University. Accessed February 27, 2021. http://hdl.handle.net/1957/9292.

MLA Handbook (7^th Edition):

Bolsinger, Travis Samuel Sebastian. “Human platelet adhesion to heparinized silica surfaces.” 2008. Web. 27 Feb 2021.

Vancouver:

Bolsinger TSS. Human platelet adhesion to heparinized silica surfaces. [Internet] [Masters thesis]. Oregon State University; 2008. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/1957/9292.

Council of Science Editors:

Bolsinger TSS. Human platelet adhesion to heparinized silica surfaces. [Masters Thesis]. Oregon State University; 2008. Available from: http://hdl.handle.net/1957/9292

21. Jovilyn Therese Baco Fajardo. Information Collection in Disaster Areas Using Participatory Sensing and Delay Tolerant Network : 参加型センシングとDTNを用いた災害地での情報収集; サンカガタセンシングト DTN オモチイタサイガイチデノジョウホウシュウシュウ.

Degree: 博士(工学), Nara Institute of Science and Technology / 奈良先端科学技術大学院大学

URL: http://hdl.handle.net/10061/9241

Subjects/Keywords: data aggregation

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APA (6^th Edition):

Fajardo, J. T. B. (n.d.). Information Collection in Disaster Areas Using Participatory Sensing and Delay Tolerant Network : 参加型センシングとDTNを用いた災害地での情報収集; サンカガタセンシングト DTN オモチイタサイガイチデノジョウホウシュウシュウ. (Thesis). Nara Institute of Science and Technology / 奈良先端科学技術大学院大学. Retrieved from http://hdl.handle.net/10061/9241

Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Fajardo, Jovilyn Therese Baco. “Information Collection in Disaster Areas Using Participatory Sensing and Delay Tolerant Network : 参加型センシングとDTNを用いた災害地での情報収集; サンカガタセンシングト DTN オモチイタサイガイチデノジョウホウシュウシュウ.” Thesis, Nara Institute of Science and Technology / 奈良先端科学技術大学院大学. Accessed February 27, 2021. http://hdl.handle.net/10061/9241.

Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Fajardo, Jovilyn Therese Baco. “Information Collection in Disaster Areas Using Participatory Sensing and Delay Tolerant Network : 参加型センシングとDTNを用いた災害地での情報収集; サンカガタセンシングト DTN オモチイタサイガイチデノジョウホウシュウシュウ.” Web. 27 Feb 2021.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Vancouver:

Fajardo JTB. Information Collection in Disaster Areas Using Participatory Sensing and Delay Tolerant Network : 参加型センシングとDTNを用いた災害地での情報収集; サンカガタセンシングト DTN オモチイタサイガイチデノジョウホウシュウシュウ. [Internet] [Thesis]. Nara Institute of Science and Technology / 奈良先端科学技術大学院大学; [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10061/9241.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.

Council of Science Editors:

Fajardo JTB. Information Collection in Disaster Areas Using Participatory Sensing and Delay Tolerant Network : 参加型センシングとDTNを用いた災害地での情報収集; サンカガタセンシングト DTN オモチイタサイガイチデノジョウホウシュウシュウ. [Thesis]. Nara Institute of Science and Technology / 奈良先端科学技術大学院大学; Available from: http://hdl.handle.net/10061/9241

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.

22. Jian, Cuiying. Molecular Dynamics Investigation on the Aggregation of Polyaromatic Compounds in Water and Organic Solvents.

Degree: PhD, Department of Mechanical Engineering, 2015, University of Alberta

URL: https://era.library.ualberta.ca/files/qj72p9692

► Aggregation of polyaromatic (PA) compounds has drawn great interest due to their wide impacts in areas such as petroleum processing. Despite the extensive studies on… (more)

▼ Aggregation of polyaromatic (PA) compounds has drawn great interest due to their wide impacts in areas such as petroleum processing. Despite the extensive studies on PA compounds, fundamental knowledge of their aggregation behaviors is still missing at atomistic level. For instance, it’s still unclear how the properties of the solvent can lead to different aggregation mechanisms and hence affect the aggregated structures of PA molecules. In this dissertation, a series of molecular dynamics (MD) simulations have been performed to investigate the effect of solute chemical structures as well as solvents on the aggregation of PA compounds. The PA molecules studied here possess the same PA core structure but have systematically varied side-chain lengths. We started with simulating a single type of PA compounds in water. Inside the aggregated structures, while some PA core stacking was observed, most of the PA molecules are simply entangled together without preferred orientations. More interestingly, it was found that side-chain length has a non-monotonic effect on the size of the aggregates, with intermediate side-chain length leading to smaller aggregates. In contrast, regardless of the side-chain length, these PA molecules aggregated into ordered structures in toluene and n-heptane, which mainly consist of stacked PA cores. On the other hand, the ranges of stacking of PA cores in these two organic solvents are different, thus resulting in distinct aggregated geometries. Following the above studies which involve only a single type of PA compounds as the solute, we explored the aggregation of mixed PA compounds of different types in toluene, n-heptane and heptol (toluene/n-heptane mixture). It was found that the inhomogeneity in solutes can enhance the stacking of PA cores, leading to the long-range stacking of PA cores. Furthermore, the existence of this long-range stacking of PA cores is insensitive to the solvents employed. Through detailed analysis of the aggregated structures, the aggregation mechanisms of different kinds of solutes were clarified. This dissertation provided insights for the aggregation of PA compounds from atomic level, and shed lights on controlling their aggregated structures.

Subjects/Keywords: Molecular dynamics; Polyaromatic compounds; Aggregation

11 more images…

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APA (6^th Edition):

Jian, C. (2015). Molecular Dynamics Investigation on the Aggregation of Polyaromatic Compounds in Water and Organic Solvents. (Doctoral Dissertation). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/qj72p9692

Chicago Manual of Style (16^th Edition):

Jian, Cuiying. “Molecular Dynamics Investigation on the Aggregation of Polyaromatic Compounds in Water and Organic Solvents.” 2015. Doctoral Dissertation, University of Alberta. Accessed February 27, 2021. https://era.library.ualberta.ca/files/qj72p9692.

MLA Handbook (7^th Edition):

Jian, Cuiying. “Molecular Dynamics Investigation on the Aggregation of Polyaromatic Compounds in Water and Organic Solvents.” 2015. Web. 27 Feb 2021.

Vancouver:

Jian C. Molecular Dynamics Investigation on the Aggregation of Polyaromatic Compounds in Water and Organic Solvents. [Internet] [Doctoral dissertation]. University of Alberta; 2015. [cited 2021 Feb 27]. Available from: https://era.library.ualberta.ca/files/qj72p9692.

Council of Science Editors:

Jian C. Molecular Dynamics Investigation on the Aggregation of Polyaromatic Compounds in Water and Organic Solvents. [Doctoral Dissertation]. University of Alberta; 2015. Available from: https://era.library.ualberta.ca/files/qj72p9692

Cornell University

23. Anderson, Valerie. Alpha-Synuclein And Enhanced Green Fluorescent Protein In Trifluoroethanol: Protective Factors Oppose Protein Aggregation.

Degree: PhD, Physics, 2011, Cornell University

URL: http://hdl.handle.net/1813/30736

► Protein aggregation, leading to the formation of amyloid fibrils, is associated with many human diseases, including Parkinson's disease, Alzheimer's disease and type II diabetes. 2,2,2-trifluoroethanol… (more)

▼ Protein aggregation, leading to the formation of amyloid fibrils, is associated with many human diseases, including Parkinson's disease, Alzheimer's disease and type II diabetes. 2,2,2-trifluoroethanol (TFE) is frequently used to induce amyloid conversion in biophysical studies, but the mechanisms underlying TFE-induced fibrillization are not yet well understood. We have measured secondary structural changes of the Parkinson's disease-associated protein [alpha]-synuclein ([alpha]S), and have discovered that TFE-induced aggregation is correlated with population of a partially structured state of the monomer protein. By investigating the pH- and temperaturedependences of the conformational transitions, we find evidence that loss of proteinsolvent interactions drives both the structural changes and the fibril production. Furthermore, we used enhanced green fluorescent protein (EGFP) as a model system to examine the effects of sequence and tertiary structure in TFE-induced aggregation, and found that the behavior of acid-denatured EGFP is qualitatively similar to [alpha]S, while tertiary structure impedes aggregation. We conclude that initiation of protein aggregation in solutions containing TFE involves overcoming multiple protective factors, rather than stabilization of specific structural elements. We identify three distinct structural states that contribute to the circular dichroism spectra of [alpha]S variants and acid-denatured EGFP. For both types of proteins, a partially [alpha]-helical conformation is populated at moderate TFE concentrations where aggregation is enhanced. The TFE-induced [alpha]S fibrils are [beta]-sheet-rich, flexible, helical structures, while the EGFP aggregates are flexible, uniform-width fibrils. At low (<10-15% v/v) TFE, the [alpha]S variants and acid-denatured EGFP undergo loss of polyproline-II structure, which is suggestive of reduced protein-water interactions. At higher TFE, preferential solvation leads to TFE coating of the proteins, stabilizing [alpha]-helical structures. The temperature response of [alpha]S reveals distinct behavior for proteins in water-like vs. TFE-like local environments. Moreover, the intermediate-TFE conformations appear to be invariant with respect to temperature and pH, which indicates that the proteins experience reduced solvent interactions at moderate [TFE]. Our results suggest that TFE reduces solvation barriers in aggregation reactions. However, aggregation pathway selection may depend on details of protein structure, and the protein sequence affects the TFE concentrations required for dehydration-driven fibrillization. Advisors/Committee Members: Webb, Watt Wetmore (chair), Nicholson, Linda K (committee member), Sethna, James Patarasp (committee member).

Subjects/Keywords: trifluoroethanol; amyloid; protein aggregation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Anderson, V. (2011). Alpha-Synuclein And Enhanced Green Fluorescent Protein In Trifluoroethanol: Protective Factors Oppose Protein Aggregation. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/30736

Chicago Manual of Style (16^th Edition):

Anderson, Valerie. “Alpha-Synuclein And Enhanced Green Fluorescent Protein In Trifluoroethanol: Protective Factors Oppose Protein Aggregation.” 2011. Doctoral Dissertation, Cornell University. Accessed February 27, 2021. http://hdl.handle.net/1813/30736.

MLA Handbook (7^th Edition):

Anderson, Valerie. “Alpha-Synuclein And Enhanced Green Fluorescent Protein In Trifluoroethanol: Protective Factors Oppose Protein Aggregation.” 2011. Web. 27 Feb 2021.

Vancouver:

Anderson V. Alpha-Synuclein And Enhanced Green Fluorescent Protein In Trifluoroethanol: Protective Factors Oppose Protein Aggregation. [Internet] [Doctoral dissertation]. Cornell University; 2011. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/1813/30736.

Council of Science Editors:

Anderson V. Alpha-Synuclein And Enhanced Green Fluorescent Protein In Trifluoroethanol: Protective Factors Oppose Protein Aggregation. [Doctoral Dissertation]. Cornell University; 2011. Available from: http://hdl.handle.net/1813/30736

24. Singh, Gurpreet. Molecular simulation studies of peptide aggregation in small finite sized systems and near surfaces.

Degree: 2009, Technische Universität Dortmund

URL: http://hdl.handle.net/2003/26021

► Die Aggregation von Proteinen spielt in verschiedenen biologischen Prozessen eine Rolle und wird insbesondere mit vielen Krankheiten wie Alzheimer, Parkinson oder Type II Diabetes Mellitus… (more)

▼ Die Aggregation von Proteinen spielt in verschiedenen biologischen Prozessen eine Rolle und wird insbesondere mit vielen Krankheiten wie Alzheimer, Parkinson oder Type II Diabetes Mellitus in Verbindung gebracht. Es wurde gezeigt, dass die Aggregation amyloidogener Proteine im Falle der Ausbildung von amyloiden Fibrillen einem keimbasierten Wachstumsmechanismus folgt. Die Aufspaltung einer wässrigen Proteinlösung in eine gesättigte Proteinlösung und feste Fibrillen, die sich miteinander im Gleichgewicht befinden, ist vergleichbar mit der Entmischung in binären Systemen. Weil die Proteinaggregation in Zellen zusätzlichen Einflüssen wie der Anwesenheit verschiedener Oberflächen und Cosolventien und einer begrenzten Zellgröße unterliegt, ist es wichtig, den Effekt dieser Einflüsse zu verstehen. Einen Beitrag zur Aufklärung kann auch durch Computersimulation von Modellpeptidfragmenten, die sich ähnlich verhalten wie das Protein, aus dem sie entnommen wurden, geleistet werden. Solche Studien haben den Vorteil, dass sie Informationen auf molekularer Ebene liefern können. In dieser Arbeit wurden die Auswirkungen einer endlichen Systemgröße, der Temperatur und der Wechselwirkung mit Oberflächen auf die Aggregation untersucht. In jeder Computersimulation, die sich mit Phasenübergängen beschäftigt, müssen Oberflächeneffekte in die überlegungen auf geeignete Weise einbezogen werden, bevor die Ergebnisse auf makroskopische Systeme übertragen werden können. Aus diesem Grunde wurde im Rahmen dieser Arbeit der Einfluss einer begrenzten Systemgröße auf die Aggregation von Peptiden mit Hilfe der molekulardynamischen Simulation wässriger Peptidlösungen unter Verwendung verschiedener Konzentrationen und Systemgrößen untersucht. In diesem Zusammenhang wurden drei verschiedene Parameter verwendet, um den Aggregationsprozess zu quantifizieren und den Aggregrationsgrad zu berechnen. Zunehmende Aggregationsgrade ließen sich durch Erhöhung der Peptidkonzentration bei gleich bleibender Systemgröße oder durch Erhöhung der Systemgröße bei gleich bleibender Peptidkonzentration erreichen. Die Abnahme des Aggregationsgrades mit der Abnahme der Systemgröße wurde auf das Auftreten eines künstlichen Zustandes zurückgeführt, in dem die weniger stark vertretene Phase, in diesem Fall das Peptidaggregat, beeinflusst wird. Sobald sich die Systemgröße an die Größe makroskopischer Systeme annähert, verschwindet dieser künstliche Zustand schließlich. Folglich wird eine Aggregation, die bei einer bestimmten Konzentration in einem makroskopischen System auftritt, bei der gleichen Konzentration in kleinen (mikroskopischen) Systemen unterdrückt. Aus den durchgeführten Studien ergeben sich hauptsächlich zwei Schlussfolgerungen: Zum einen hat die endliche Systemgröße einen drastischen Einfluss auf die Aggregation von Peptiden und ist verantwortlich für die Instabilität von Aggregaten, die aus nur wenigen Peptiden bestehen. Wie bereits oben angesprochen, muss dies bei der übertragung auf makroskopische Systeme berücksichtigt werden. Zum anderen ist auch klar,… Advisors/Committee Members: Winter, Roland.

Subjects/Keywords: Molecular simulation; Peptide aggregation; 540

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APA (6^th Edition):

Singh, G. (2009). Molecular simulation studies of peptide aggregation in small finite sized systems and near surfaces. (Thesis). Technische Universität Dortmund. Retrieved from http://hdl.handle.net/2003/26021

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Singh, Gurpreet. “Molecular simulation studies of peptide aggregation in small finite sized systems and near surfaces.” 2009. Thesis, Technische Universität Dortmund. Accessed February 27, 2021. http://hdl.handle.net/2003/26021.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Singh, Gurpreet. “Molecular simulation studies of peptide aggregation in small finite sized systems and near surfaces.” 2009. Web. 27 Feb 2021.

Vancouver:

Singh G. Molecular simulation studies of peptide aggregation in small finite sized systems and near surfaces. [Internet] [Thesis]. Technische Universität Dortmund; 2009. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/2003/26021.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Singh G. Molecular simulation studies of peptide aggregation in small finite sized systems and near surfaces. [Thesis]. Technische Universität Dortmund; 2009. Available from: http://hdl.handle.net/2003/26021

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

25. Samra, Stefan Basil. NUMERICAL IMPLEMENTATION OF A CONTINUUM PLATELET AGGREGATION MODEL .

Degree: 2011, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/11932

► A continuum stress transport model of platelet aggregation from the literature [14], [16], [15], and [18] is presented and solved numerically. The model is a… (more)

▼ A continuum stress transport model of platelet aggregation from the literature [14], [16], [15], and [18] is presented and solved numerically. The model is a single-scale reduction of a multi-scale model and utilizes the incompressible Navier-Stokes equations with a Newtonian constituative relationship to govern blood ow. Other �eld variables including platelet and chemical activator concentrations exist with partial di�erential equations governing their transport. The platelet aggregation model is closely related to the model of the viscoelastic Oldroyd-B uid, which is discussed. The focus of this thesis is on the numerical solution of the Oldroyd-B equations and the equations comprising the platelet aggregation model using a �nite volume formulation within an existing open source Computational Fluid Dynamics platform. Pressure-velocity coupling is achieved using the PISO Algorithm while the remaining model equations are solved sequentially. In the �rst class of simulations, the ow of an Oldroyd-B uid is solved within a two dimen- sional planar domain. The viscous and elastic properties of the uid are varied in an e�ort to observe the model's resulting behavior. Exact solutions for the transient and steady-state ow of an Oldroyd-B uid are used for the purpose of validating the numerical approach. Numerical solutions are observed to correspond well with exact solutions for a range of parameter sets. Solution divergence is observed under certain conditions, speci�cally for uids with high Weis- senberg numbers and elastic moduli. In the second class of simulations, the platelet aggregation model is solved within the same domain as the Oldroyd-B simulations. Clot growth is observed but solution divergence occurs in the presence of growth of the model's stress tensor �eld. By limiting certain model parameters it is shown that numerical stability can be improved. Using this approach, the sensitivity of results to various model parameters is investigated. Finally, a preliminary investigation of the application of the model to the clinically important case of clot growth within stagnant and recirculating ows is presented. Advisors/Committee Members: Eric G Paterson, Thesis Advisor/Co-Advisor, Eric G Paterson, Thesis Advisor/Co-Advisor.

Subjects/Keywords: openfoam; platelet aggregation; thrombosis; numerical

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APA (6^th Edition):

Samra, S. B. (2011). NUMERICAL IMPLEMENTATION OF A CONTINUUM PLATELET AGGREGATION MODEL . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/11932

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Samra, Stefan Basil. “NUMERICAL IMPLEMENTATION OF A CONTINUUM PLATELET AGGREGATION MODEL .” 2011. Thesis, Penn State University. Accessed February 27, 2021. https://submit-etda.libraries.psu.edu/catalog/11932.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Samra, Stefan Basil. “NUMERICAL IMPLEMENTATION OF A CONTINUUM PLATELET AGGREGATION MODEL .” 2011. Web. 27 Feb 2021.

Vancouver:

Samra SB. NUMERICAL IMPLEMENTATION OF A CONTINUUM PLATELET AGGREGATION MODEL . [Internet] [Thesis]. Penn State University; 2011. [cited 2021 Feb 27]. Available from: https://submit-etda.libraries.psu.edu/catalog/11932.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Samra SB. NUMERICAL IMPLEMENTATION OF A CONTINUUM PLATELET AGGREGATION MODEL . [Thesis]. Penn State University; 2011. Available from: https://submit-etda.libraries.psu.edu/catalog/11932

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Victoria University of Wellington

26. Magana-Rodriguez, Benjamin. Are Distribution Patterns Correlated with Plant Traits?.

Degree: 2012, Victoria University of Wellington

URL: http://hdl.handle.net/10063/2229

► The current crisis in loss of biodiversity requires rapid action. Knowledge of species' distribution patterns across scales is of high importance in determining their current… (more)

▼ The current crisis in loss of biodiversity requires rapid action. Knowledge of species' distribution patterns across scales is of high importance in determining their current status. However, species display many different distribution patterns on multiple scales. A positive relationship between regional (broad-scale) distribution and local abundance (fine-scale) of species is almost a constant pattern in macroecology. Nevertheless interspecific relationships typically contain much scatter. For example, species that possess high local abundance and narrow ranges, or species that are widespread, but locally rare. One way to describe these spatial features of distribution patterns is by analysing the scaling properties of occupancy (e.g., aggregation) in combination with knowledge of the processes that are generating the specific spatial pattern (e.g., reproduction, dispersal, and colonisation). The main goal of my research was to investigate if distribution patterns correlate with plant life-history traits across multiple scales. First, I compared the performance of five empirical models for their ability to describe the scaling relationship of occupancy in two datasets from Molesworth Station, New Zealand. Secondly, I analysed the association between spatial patterns and life history traits at two spatial scales in an assemblage of 46 grassland species in Molesworth Station. The spatial arrangement was quantified using the parameter k from the Negative Binomial Distribution (NBD). Finally, I investigated the same association between spatial patterns and life-history traits across local, regional and national scales, focusing in one of the most diverse families of plant species in New Zealand, the Veronica sect. Hebe (Plantaginaceae). The spatial arrangement was investigated using the mass fractal dimension. Cross-species correlations and phylogenetically independent contrasts were used to investigate the relationships between plant life-history traits and spatial patterns on both data bases. There was no superior occupancy-area model overall for describing the scaling relationship, however the results showed that a variety of occupancy-area models can be fit to different data sets at diverse spatial scales using nonlinear regression. Additionally, here I showed that it is possible to deduce and extrapolate information on occupancy at fine scales from coarse-scale data. For the 46 plantassemblage in Molesworth Station, Specific leaf area (SLA) exhibits a positive association with aggregation in cross-species analysis, while leaf area showed a negative association, and dispersule mass a positive correlation with degree of aggregation in phylogenetic contrast analysis at a local-scale (20 × 20 m resolution). Plant height was the only life-history trait that was associated with degree of aggregation at a regional-scale (100 × 60 mresolution). For the Veronica sect. Hebe dataset, leaf area showed a positive correlation with aggregation while specific leaf area showed a negative correlation with aggregation at a fine… Advisors/Committee Members: Hartley, Stephen, Garnock-Jones, Phil, Moles, Angela.

Subjects/Keywords: Distribution patterns; Plant traits; Aggregation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Magana-Rodriguez, B. (2012). Are Distribution Patterns Correlated with Plant Traits?. (Doctoral Dissertation). Victoria University of Wellington. Retrieved from http://hdl.handle.net/10063/2229

Chicago Manual of Style (16^th Edition):

Magana-Rodriguez, Benjamin. “Are Distribution Patterns Correlated with Plant Traits?.” 2012. Doctoral Dissertation, Victoria University of Wellington. Accessed February 27, 2021. http://hdl.handle.net/10063/2229.

MLA Handbook (7^th Edition):

Magana-Rodriguez, Benjamin. “Are Distribution Patterns Correlated with Plant Traits?.” 2012. Web. 27 Feb 2021.

Vancouver:

Magana-Rodriguez B. Are Distribution Patterns Correlated with Plant Traits?. [Internet] [Doctoral dissertation]. Victoria University of Wellington; 2012. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10063/2229.

Council of Science Editors:

Magana-Rodriguez B. Are Distribution Patterns Correlated with Plant Traits?. [Doctoral Dissertation]. Victoria University of Wellington; 2012. Available from: http://hdl.handle.net/10063/2229

University of Miami

27. Lopez, Christopher J. Part I. NMR Studies of Aggregation in Organic Dyes and Salts Part II. Design of Relaxation and Diffusion Selective Pulses.

Degree: PhD, Chemistry (Arts and Sciences), 2014, University of Miami

URL: https://scholarlyrepository.miami.edu/oa_dissertations/1348

► Part I. Small organic molecules can play important medicinal roles as markers for antitumor agents, drug delivery, drug discovery, and proteins. However, many small… (more)

Subjects/Keywords: Aggregation of small organic molecules

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lopez, C. J. (2014). Part I. NMR Studies of Aggregation in Organic Dyes and Salts Part II. Design of Relaxation and Diffusion Selective Pulses. (Doctoral Dissertation). University of Miami. Retrieved from https://scholarlyrepository.miami.edu/oa_dissertations/1348

Chicago Manual of Style (16^th Edition):

Lopez, Christopher J. “Part I. NMR Studies of Aggregation in Organic Dyes and Salts Part II. Design of Relaxation and Diffusion Selective Pulses.” 2014. Doctoral Dissertation, University of Miami. Accessed February 27, 2021. https://scholarlyrepository.miami.edu/oa_dissertations/1348.

MLA Handbook (7^th Edition):

Lopez, Christopher J. “Part I. NMR Studies of Aggregation in Organic Dyes and Salts Part II. Design of Relaxation and Diffusion Selective Pulses.” 2014. Web. 27 Feb 2021.

Vancouver:

Lopez CJ. Part I. NMR Studies of Aggregation in Organic Dyes and Salts Part II. Design of Relaxation and Diffusion Selective Pulses. [Internet] [Doctoral dissertation]. University of Miami; 2014. [cited 2021 Feb 27]. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/1348.

Council of Science Editors:

Lopez CJ. Part I. NMR Studies of Aggregation in Organic Dyes and Salts Part II. Design of Relaxation and Diffusion Selective Pulses. [Doctoral Dissertation]. University of Miami; 2014. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/1348

University of Houston

28. Kundooru, Shyam Sunder Reddy 1991-. Generalized Framework for Time-Sensitive Decision Support Systems.

Degree: MS, Computer Science, 2015, University of Houston

URL: http://hdl.handle.net/10657/1739

► The University of Houston has various monitoring systems that feed information to Emergency Operations Centers for emergency decisions. Emergency decisions must be made utilizing the… (more)

Subjects/Keywords: Data Integration; Data Aggregation

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APA (6^th Edition):

Kundooru, S. S. R. 1. (2015). Generalized Framework for Time-Sensitive Decision Support Systems. (Masters Thesis). University of Houston. Retrieved from http://hdl.handle.net/10657/1739

Chicago Manual of Style (16^th Edition):

Kundooru, Shyam Sunder Reddy 1991-. “Generalized Framework for Time-Sensitive Decision Support Systems.” 2015. Masters Thesis, University of Houston. Accessed February 27, 2021. http://hdl.handle.net/10657/1739.

MLA Handbook (7^th Edition):

Kundooru, Shyam Sunder Reddy 1991-. “Generalized Framework for Time-Sensitive Decision Support Systems.” 2015. Web. 27 Feb 2021.

Vancouver:

Kundooru SSR1. Generalized Framework for Time-Sensitive Decision Support Systems. [Internet] [Masters thesis]. University of Houston; 2015. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10657/1739.

Council of Science Editors:

Kundooru SSR1. Generalized Framework for Time-Sensitive Decision Support Systems. [Masters Thesis]. University of Houston; 2015. Available from: http://hdl.handle.net/10657/1739

University of Colorado

29. Cordes, Amanda. Complex Stability Behavior in Novel Protein Constructs: Aggregation of Fc- and HSA- Based Fusion Proteins.

Degree: PhD, Chemical & Biochemical Engineering, 2011, University of Colorado

URL: https://scholar.colorado.edu/chbe_gradetds/20

► The development of protein based biopharmaceuticals has resulted in the ability to treat many serious conditions, including endogenous protein deficiencies, cancer and autoimmune disorders.… (more)

▼ The development of protein based biopharmaceuticals has resulted in the ability to treat many serious conditions, including endogenous protein deficiencies, cancer and autoimmune disorders. However, in order to be successful drug candidates, these more complex molecules require stable formulations that can last from manufacturing through transportation to patient administration. Fusion proteins, which are constructed from unrelated proteins or protein domains, present additional formulation challenges. In these proteins, domains did not co-evolve for stability and thus conditions favoring the stability of one domain may destabilize the other. Our current hypotheses are that the least stable protein will also be the least stable domain in the fusion and that selective stabilization of this least stable domain can be used to reduce overall aggregation of the fusion protein, with preferential binding of cosolutes to the native state being one method of achieving selective domain stabilization. Abatacept, an Fc-CTLA4 fusion protein, is used as a model to investigate the stability behavior of Fc fusion proteins. Fc-CTLA4 exhibits markedly different aggregation rates with only a small shift in pH. Changing from pH 7.5 to pH 6 causes a two order of magnitude increase in rate of monomer loss during incubation at 40 °C. The aggregation behavior during accelerated stability studies at elevated temperature was found to be controlled by conformational instability of the protein. Conditions which destabilized the CTLA4 domain and the C_H2 portion of the Fc domain lead to a decreased activation energy for aggregation and an increased aggregation rate. Fc-CTLA 4 was also studied to examine how conditions which increase conformational stability impact the progression of aggregation due to other physical stresses (e.g., exposure to air/water and water/ice interfaces and freeze concentration during freezing). No changes were detected in the amount of monomer lost or number of particles formed between solution conditions at pH 6.0 and pH 7.5, despite large differences in conformational stability under these solution conditions. Two HSA fusion proteins (HSA-hGH and HSA-GCSF) were studied to investigate small molecule ligand binding as a selective stabilization strategy, with octanoic acid used as the ligand. Addition of octanoic acid resulted in increased conformational stability for HSA, HSA-hGH and HSA-GCSF. Repulsive protein-protein interactions were only increased for HSA and HSA-hGH; HSA-GCSF protein-protein interactions remained unchanged. Reductions in aggregation were seen in the case of HSA-hGH. Thus it appears that specific binding to a domain of a fusion protein can reduce aggregation in more than one way (i.e. increasing both colloidal and conformational stability). No changes in HSA-GCSF aggregation were observed with the addition of octanoic acid, despite the increases in conformational stability, indicating the ligand binding stabilization approach does not appear to be… Advisors/Committee Members: Theodore W. Randolph, John F. Carpenter, Richard D. Noble.

Subjects/Keywords: Aggregation; Formulation; Protein; Chemical Engineering

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Cordes, A. (2011). Complex Stability Behavior in Novel Protein Constructs: Aggregation of Fc- and HSA- Based Fusion Proteins. (Doctoral Dissertation). University of Colorado. Retrieved from https://scholar.colorado.edu/chbe_gradetds/20

Chicago Manual of Style (16^th Edition):

Cordes, Amanda. “Complex Stability Behavior in Novel Protein Constructs: Aggregation of Fc- and HSA- Based Fusion Proteins.” 2011. Doctoral Dissertation, University of Colorado. Accessed February 27, 2021. https://scholar.colorado.edu/chbe_gradetds/20.

MLA Handbook (7^th Edition):

Cordes, Amanda. “Complex Stability Behavior in Novel Protein Constructs: Aggregation of Fc- and HSA- Based Fusion Proteins.” 2011. Web. 27 Feb 2021.

Vancouver:

Cordes A. Complex Stability Behavior in Novel Protein Constructs: Aggregation of Fc- and HSA- Based Fusion Proteins. [Internet] [Doctoral dissertation]. University of Colorado; 2011. [cited 2021 Feb 27]. Available from: https://scholar.colorado.edu/chbe_gradetds/20.

Council of Science Editors:

Cordes A. Complex Stability Behavior in Novel Protein Constructs: Aggregation of Fc- and HSA- Based Fusion Proteins. [Doctoral Dissertation]. University of Colorado; 2011. Available from: https://scholar.colorado.edu/chbe_gradetds/20

30. Oberholtzer, Zachary Ray. Population of Tau Embedded in Parallel β-Sheets Depends on Heparin Stoichiometry.

Degree: 2015, University of California – eScholarship, University of California

URL: http://www.escholarship.org/uc/item/10x31901

► The aggregation of the human tau protein is heavily implicated in the progression of Alzhiemer’s Disease. In this study we examined the aggregation kinetics of… (more)

▼ The aggregation of the human tau protein is heavily implicated in the progression of Alzhiemer’s Disease. In this study we examined the aggregation kinetics of a truncated segment of the longest tau isoform, Tau 187, and induced aggregation with the polyanion hepain. We applied cw-EPR in order to quantitatively measure the population of tau embedded in parallel β-sheet structure and compared these measurements to traditional kinetic measurement techniques, Tht fluorescence and turbidity. Cw-EPR revealed rapid formation of parallel β-sheet structure early in the aggregation process well before fibrils are thought to appear. We observe a large population of spins first exhibits reduced mobility upon mixing with heparin, which is later followed by an increase in β-sheet structure consistent with proposed models of nucleation followed by structural rearrangement. Additionally, comparing cw-EPR with Tht fluorescence demonstrates Tht binding is non-linear with respect to parallel β-sheet structure and the precise binding structure of Tht remains unclear. The transfer of tau pathology from infected to healthy cells has been well established by the literature, however, little is known about the relationship between seed structure and seeding efficacy. Here we investigated the importance of β-sheet content as detected by cw-EPR on seeding efficacy, but were unable to establish a relationship due to the overriding effect of heparin. Previously our group has observed a conformational shift around the PHF6* hexapeptide from compact to extended state and we examined the stoichiometric effect of heparin on this extension to determine the potency of heparin for inducing changes in the tau system. Finally, dependence of tau aggregation kinetics on heparin stoichiometry was investigated. We discovered the extent of observable distance change depended on heparin stoichiometry, however, even dilute quantities of heparin are able to induce significant extension around the PHF6* hexapeptide. The amount of total fibril formation was also found to depend on the heparin stoichiometry with lower heparin concentrations generating less total fibril content. Our findings suggests even minute quantities of heparin exerts great influence on the tau system and future work will require ways of working around or limiting heparin’s influence in order to directly probe the underlying fundamentals of tau aggregation.

Subjects/Keywords: Chemical engineering; Aggregation; Tau

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APA (6^th Edition):

Oberholtzer, Z. R. (2015). Population of Tau Embedded in Parallel β-Sheets Depends on Heparin Stoichiometry. (Thesis). University of California – eScholarship, University of California. Retrieved from http://www.escholarship.org/uc/item/10x31901

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Oberholtzer, Zachary Ray. “Population of Tau Embedded in Parallel β-Sheets Depends on Heparin Stoichiometry.” 2015. Thesis, University of California – eScholarship, University of California. Accessed February 27, 2021. http://www.escholarship.org/uc/item/10x31901.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Oberholtzer, Zachary Ray. “Population of Tau Embedded in Parallel β-Sheets Depends on Heparin Stoichiometry.” 2015. Web. 27 Feb 2021.

Vancouver:

Oberholtzer ZR. Population of Tau Embedded in Parallel β-Sheets Depends on Heparin Stoichiometry. [Internet] [Thesis]. University of California – eScholarship, University of California; 2015. [cited 2021 Feb 27]. Available from: http://www.escholarship.org/uc/item/10x31901.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Oberholtzer ZR. Population of Tau Embedded in Parallel β-Sheets Depends on Heparin Stoichiometry. [Thesis]. University of California – eScholarship, University of California; 2015. Available from: http://www.escholarship.org/uc/item/10x31901

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Open Access Theses and Dissertations