Interleukin-1beta folding and aggregation

Finke, John Mason University of California, San Diego 2001 해외박사(DDOD)

To understand more fully the process of protein aggregation, protein folding and aggregation experiments were conducted on the wild-type sequence of the all β-sheet protein human interleukin-1β and compared to similar experiments on an aggregation prone interleukin-1β mutant, K97I. Wild-type interleukin-1β and the mutant K97I demonstrated similar thermodynamic stability to chemical denaturation. Wild-type interleukin-1β and the mutant K97I also demonstrated similar folding kinetics, best characterized by the 3-state mechanism U <math> <f> <stk><lyr>→^{<b>k<inf>UI</inf></b>}</lyr><lyr>←<inf> <rm>k<inf>IU</inf></rm></inf></lyr></stk></f> </math> I <math> <f> <stk><lyr>→^{<rm>k<inf>IN</inf></rm>}</lyr><lyr> ←<inf><rm>k<inf>NI</inf></rm></inf></lyr></stk></f> </math> N, where U is an unfolded ensemble, I is an intermediate ensemble with stable structure in β-strands 4–10, and N is the native state of interleukin-1β with all 12 β-strands folded. Despite these similarities, K97I demonstrates a much greater degree of aggregation than wild-type interleukin-1β during refolding at higher concentrations, measured directly by light scattering and indirectly by the loss of soluble protein. Kinetic measurements of K97I aggregation reveal that aggregation initiates predominantly from states in the unfolded ensemble, U. To address when, during the process of protein folding, protein can be “rescued” from the aggregated state, commitment experiments were developed as a novel application of isotopic labeling and mass spectrometry. Commitment-to-folding experiments determined that the native state, N, of interleukin-1β is irreversible to aggregation. Commitment-to-aggregation experiments determined that aggregation proceeds through the early formation of reversible non-committed aggregates, A_LS, followed by slow formation of irreversible committed aggregates, A_C. The rate of formation of early aggregates, A_LS, is highly dependent on the concentration of protein whereas the rate of formation of A_C demonstrates first-order kinetics. Further kinetic studies of interleukin-1β aggregation, measured with ANS-fluorescence, strongly indicate the presence of a smaller reversible aggregate ensemble, A_ANS, preceding formation of aggregates detected with light scattering, A_LS. Mixed wild-type and K97I aggregation studies indicate that wild-type interleukin-1β will co-aggregate with committed K97I aggregates, A_C, but appear not to bind to the non-committed aggregates, A_LS. Ultimately, compounds were mixed with refolding wild-type and K97I to determine whether aggregation could be increased or decreased with “drug-like” additives. It was shown that sucrose inhibits and hydrophobic peptides promote interleukin-1β aggregation. Using these aggregation studies, a mechanism of interleukin-1β aggregation was proposed as a context for further studies.

Untersuchung der Gelierung von Polyacrylnitril mit Hilfe der Rontgen- und Neutronenstreuung

Finke, Vera Univ. Hamburg 1990 국내박사

Verschiedene Wirkungen von Alkylxanthinen auf das mukosale cyclische AMP und resorptive Eigenschaften am Jejunum der Ratte in vitro

Finke, Doris Univ. Hamburg 1989 국내박사

Resource and space constrained project scheduling

Finke, Daniel A The Pennsylvania State University 2010 해외박사(DDOD)

Production planning in large-scale industries such as construction and shipbuilding is a key component in the manufacturing process and has a significant effect on the overall cost and schedule of the final product. This is due to the fact that the successful fabrication of these products requires a significant amount of material and resources, all of which must be coordinated and appropriately scheduled. Project scheduling methods have been used to model and schedule activities in these industries with great success. Until recently, spatial resources, such as floor space and interior space, have not been taken into consideration in the planning phase of a project. Traditionally, spatial conflicts have been resolved locally as they occur, often resulting in costly schedule delays. This thesis develops a framework to model space in a project scheduling problem comprised of installation activities within the interior of a large-scale product. The objective is to find a schedule with near-minimum makespan. The installation project activities are constrained by precedence relationships and limited resource availabilities. Space is modeled as a special resource. The space modeling approach approximates the space required by the activities and uses those space requirements to calculate spatial conflicts. Space conflicts are incorporated via a congestion function, which increases the duration of the installation activities with overlapping spatial requirements, reflecting productivity losses due to interference. The congestion function is based on the conflict volume and the length of time the conflict occurs. A prototype software application is developed from the framework to demonstrate the feasibility of the method. A hypothetical problem and a case study problem are solved using the application. The results show that considering spatial constraints increased the project makespan from 7% to 16% for the hypothetical problems and 35% for the case study problem. The developed framework establishes an integrated methodology to model the effects of worker and activity space congestion during schedule generation. In previous work, space conflicts were identified after the schedule was completed and resolved manually. The congestion function developed in this thesis explicitly considers types of space and the volume and time duration of conflicts among types. Previous work has either modeled multiple space types without estimating the effect on activity duration, or created a single function independent of space type. By incorporating realistic space requirements and considering the effect of spatial conflicts during schedule generation, a more realistic project schedule can be created that limits costly schedule delays attributed to less detailed planning practices. Congestion is inherently present in installation projects and has been managed by front line supervisors with little help from formal scheduling tools. The framework developed in this thesis enables front line supervisors to account for and control congestion to minimize schedule delays and project costs.

Applying Patriotic and National Songs to American Elementary Music Education Curricular Standards

Finke, Ashley Virginia Liberty University ProQuest Dissertations & Theses 2022 해외박사(DDOD)

Despite existing literature documenting patriotism and nationalism in education and children’s knowledge of patriotic and national songs, the impact of patriotism and nationalism in American elementary music education through patriotic and national songs has not been examined in the context of current national standards. This examination is important as knowledge of patriotism, nationalism, and patriotic and national, specifically state, songs inform individuals’ understanding of culture and national and personal identities. This study identifies educational perspectives of educational scholars, music educators, and policy makers on patriotism, nationalism, and patriotic and national songs. A qualitative design and historical approach were utilized to infer connections and influences not acknowledged previously between patriotism, nationalism, and music education. Perspectives on development, religious foundation, need for American music preservation, and interest conflicts between music education scholars and educational representatives developed as themes through examination of select literature. Existing documents, statements, and literature were examined for themes of patriotism and nationalism to demonstrate the impact in the music education curricular structure through sample lesson plans. This work is important because development of loyalty, national identity, and knowledge result from applying patriotic and nationalistic concepts, songs, and supplementary materials in music education curriculum. Due to the instability of American patriotism, this study could benefit social sciences studies to improve instructional practices. Further implications from this study include improved teaching and expanded knowledge of patriotic and national songs; designating patriotism and nationalism in music education goals, standards, and curriculum development; and developing elementary students’ patriotic and national identities.

A worksite examination of the transtheoretical model in exercise

Fink, Christopher L The Ohio State University 2007 해외박사(DDOD)

The purpose of this study was to test the ability of 3-month and 6-month changes in the components of the transtheoretical model (TTM-stages of change, processes of change, self-efficacy, decisional balance) to predict 6-month inactive to active stage transition in a randomly selected worksite sample (N=60). Participants completed a webbased survey at baseline, 3 months, and 6 months. The results indicated that changes in behavioral processes of change from baseline to 3 months, changes in self-efficacy and behavioral processes of change from 3 to 6 months, and self-efficacy, cognitive processes of change, and decisional balance-cons were significant predictors (p<.05) of 6-month stage transition. The findings cast some doubt on the rigidity of the 6-month component in the TTM, as well as the idea that behavioral processes of change are most important in the change process during the later stages.

Flavonoid intake and breast cancer incidence and survival

Fink, Brian N The University of North Carolina at Chapel Hill 2006 해외박사(DDOD)

Background. Flavonoids are phytochemicals found in a variety of foods that have demonstrated anti-carcinogenic properties in experimental studies. Two epidemiologic studies conducted in the Mediterranean have observed an inverse association between dietary intake of certain flavonoid classes and breast cancer incidence. However, it is unknown whether a similar association is evident among American women. Further, whether flavonoids affect breast cancer survival is unknown. We investigated whether dietary flavonoid intake influences breast cancer incidence and survival among a population-based cohort of American women. Methods. A population-based, case-control study was conducted among women ages 20-98 years who resided in Nassau and Suffolk counties in Long Island, New York. Cases were newly diagnosed with a first invasive breast cancer between August 1, 1996 and July 31, 1997; controls were identified using random digit dialing and Health Care Finance Administration rosters. Trained interviewers administered an in-person questionnaire to participants on known and suspected breast cancer risk factors. Participants also completed a self-administered food frequency questionnaire regarding their average frequency of food and beverage consumption in the prior 12 months. For those with known menopausal status, 1,434 breast cancer cases and 1,440 controls provided adequate dietary responses. Case medical records were obtained to assess tumor characteristics and initial course of treatment. Cases were followed-up through 2002. All-cause mortality (n = 173) and breast cancer-specific mortality (n = 113) were determined through the National Death Index. Results. Increasing intake of flavonols, flavones, flavan-3-ols, and lignans, as reported at the case-control interview, was associated with a reduced risk of incident post-menopausal breast cancer among Long Island women. All-cause mortality among post-menopausal women was reduced for intake of flavones and isoflavones and similar results were observed for breast cancer-specific mortality. Conclusion. Findings provide evidence for a beneficial effect of flavones, flavonols and lignans on breast cancer incidence among post-menopausal women. Results from the follow-up study indicate that mortality among post-menopausal breast cancer patients is reduced in association with high intake of flavones and isoflavones near the time of diagnosis. These findings suggest American women can consume sufficient levels of flavonoid-rich foods to benefit from their potential chemopreventive effects.

Option hedging and parameter estimation when volatility is stochastic

Fink, Jason Douglas University of Virginia 2002 해외박사(DDOD)

This dissertation has two related aims. First, we improve upon the static hedging methodology of Derman, Ergener, and Kani (1995), to allow a satisfactory hedge when the stochastic process of the underlying asset exhibits a particular form of stochastic volatility. Second, we provide evidence that incorporating of hedging information into a least squares estimation procedure of a particular stochastic volatility model improves the mates of the parameters, and reduces out-of-sample error in pricing and hedging options. In Chapter Two we propose a generalized static hedge. This generalization allows the underlying asset of a barrier option to follow a stochastic process in which the volatility of the underlying asset is random. We use Monte Carlo simulations to compare this generalized hedge to existing static hedges. These simulations suggest that the generalized hedge is a significant improvement over hedges that are unmodified to reflect stochastic volatility. We find that the replicating portfolio given by the generalized static hedge gives better matches for price, delta, and vega of a barrier option than existing static hedges. Chapter Three compares an estimation of the parameters of the stochastic volatility model of Heston (1993) using only pricing information, with an estimation using both pricing and hedging information. We show that incorporating hedging information into a least-squares procedure decreases the standard errors of the parameters of the Heston model. In Chapter Four we extend the results of Chapter Three. First, a method by which we choose the weight to be placed on the hedging information in the estimation of the Heston model is proposed. Second, an out-of-sample comparison is made between the hedging effectiveness of the Heston model using parameters estimated exclusively with pricing information and parameters estimated with both pricing and hedging information, where the hedging information is given the optimal weight. We find that the latter procedure reduces the out-of-sample hedging error in every metric we evaluate.

Songs of October

Fink, Simon The University of Chicago 2010 해외박사(DDOD)

Songs of October is a song cycle presented from the perspectives of two people entangled in a complicated emotional bond. The cycle begins and ends after--or perhaps in the midst of--an important crossroads or rupture in their relationship. In between, the music journeys through various states of feeling and recollection. The texts come from a variety of poets from around the first half of the 20th century and together form a dramatic dialogue between the two individuals. The cycle is composed for soprano, tenor, and a mixed chamber ensemble of ten musicians. Altogether, its 10 songs last approximately 26 minutes in duration.

Data-Driven Sourcing: How Journalists Use Digital Search Tools to Decide What's News

Fink, Katherine Columbia University 2014 해외박사(DDOD)

This dissertation examines the efforts of journalists to expand their pool of potential sources beyond a group of people often called "the usual suspects." This group consists of public officials, business leaders, experts, spokespeople, and other people who are in the news often. Using interviews, participant observation, a survey, and online ethnography, this research investigates how a growing skepticism of the usual suspects and increasingly powerful technology have led to innovations in the source search process. Some journalists have seen potential in digital search tools, including databases and social media, for finding sources that had once been too difficult or time-consuming to find. Journalists themselves have created two source-finding initiatives: a database called the Public Insight Network, and Storyful, which calls itself the "world's first social news agency." Storyful journalists specialize in finding and verifying social media content from the scenes of breaking news events. Journalists have also used other tools created by public relations professionals and technologists. How did the availability of these tools change the reporting process? It varied by tool, and by journalist. Although the tools were designed to do similar things, journalists used them in different ways. This dissertation examines how journalists used these tools in three stages of the reporting process: finding sources, verifying sources, and managing sources. Ultimately, most journalists used these tools not to find new sources, but to follow and research sources they had already identified by name or location. Few journalists had discovered new sources and story ideas with the help of digital search tools. So while these tools opened new possibilities for finding sources, journalists were still more likely to cover some people and topics over others.