Fluorogenic Derivatization of Pro-Quinoidal Species: From Biogenic Amines to Protein Bound 3-Nitrotyrosine

The focuses of this dissertation are an examination and advancement of chemistries for the fluorogenic derivatization of the analysis of proquiniodal species. The term proquinoidal species specifically refers to a group of biologically active compounds that easily may be oxidized to the corresponding quinones or imino-quinones. Catechols (Cs), catecholamines (CAs), and 5-hydroxyindoles (5-HIs) are classes of biogenic amines that affect neuroregulatory functions such as mood and appetite. While the determination of these classes of substances has been the accomplished by a variety of techniques over the past several decades, a recent approach has been their conversation to a fluorescent product by use of the fluorogenic reagents benzylamime (BA) or diphenylethylenediamine (DPE). In the first section of this work, a critical examination of these derivatization chemistries is undertaken through product isolation, derivatization kinetics investigations, and yield determination for three substances that represent each analyte class. While not investigated in detail, it is recognized that 3-nitrotyrosine residues in peptides and proteins (a post-translational modification that has been associated with various age related pathologies such as atherosclerosis, neuropathies and others conditions), when reduced to the corresponding 3-aminotyrosine residues, undergo an analogous derivatization reaction to the catechol class. Application of the described derivatization reaction to such substances is an obvious and valuable extension of the present findings. Results obtained from the initial finding indicated that improvements regarding the physical-chemical properties of the DPE and/or BA regents would be highly useful in future applications directed toward the analysis of 3-nitrotyrosine residues, particularly as regards solubility and selective isolation of the formed product. The approach described herein relies on the reduction of the 3-NY residue to the corresponding 3-aminotyrosine (3-AY), with subsequent derivatization by either BA or DPE. Enhancement of the existing derivatization reagents is explored through chemical modification of the reagents through the attachment of various substituents for the purpose of enhanced isolation and/or detection, increasing reagent aqueous solubility, maximization of single production formation, and allowing for the incorporation of stable isotopes. Recognizing that samples of biological origin are present as a complex mixture, further to the alluded to selectivity achieved via reagent design, significant improvements of chromatographic peak capacity were additionally sought. Efforts toward this goal included the fabrication of an Extreme Ultra-Pressure Liquid Chromatography (XUPLC) system, which utilized long columns packed with sub-2µm particles (75 µm id x 0.5-2.0 m L; packed with 1.9 µm BEH C18 particles) necessitating operation at 30,000 psi. An overall goal was the integration of the results obtained from these two differing but complimentary research areas. The derivatization investigations revealed the derivatization reactions to be complete with 2 hours, with yields for Cs of no less than 70% when either reagent, BA or DPE, was utilized. Further reagent design and evaluation efforts were directed toward the characterization of BA and DPE that was elaborated to possess a sulfonic acid moiety, which provided for enhanced aqueous solubility and a selective sample preparation handle via strong anion exchange solid phase extraction. An alternate approach was the elaboration of each base regent to the dimethylamino-analog, again with the motivation being enhanced aqueous solubility but now potentially better electrospray ionization properties for mass spectrometry. Efforts in the XUPLC area revealed the expected gain in resolution and concurrent increased peak capacity. In summary, this dissertation describes advances in the utilization of existing reagents, the preparation and characterization of new reagent analogs and describes an advanced chromatographic system. All of these aspects are expected to be of high valuable in the analytical chemistry of catechol determinations and the related area of 3-nitrotyrosine residues present in peptides and proteins

The Effect of Balance Training in Healthy Subjects as Assessed by the Neurocom Balance Master

Balance is a critical component in maintaining optimal function in daily activities, and it is a skill that is frequently affected in individuals who have experienced some type of neurological, vestibular, orthopedic, or musculoskeletal deficit. A successful balance training program that can be used to improve such a person\u27s balance can be of great use and importance to a patient and a therapist. Studies have shown that balance can be improved in subjects with deficits, however little is known about the effects of training on individuals that lack balance impairments. The purpose of this study was to determine if healthy individuals could show a significant improvement in components of unilateral stance (test of static steadiness) and limits of stability (test of dynamic stability) as assessed by the Neurocom® Balance Master (NBM®). Additionally, the study will also determine if different balance treatment approaches had different outcomes in the subjects\u27 results. Thirty-six subjects (8 males, 28 females) were assessed on the NBM® and divided into the following three groups: a control group (Group 0), a balance training group (Group 1), and a balance training group that used the Bodyblade® (Group 2). The two training groups participated in balance training programs for a five-week period, and the control group did not. After the five-week period all subjects were retested on the NBM® to determine if there was a statistically significant change or improvement in their data from the initial assessment. Data was also analyzed to determine if any of the groups had significantly more improvement than any of the others. After the completion of the second assessment, the data was analyzed statistically at an alpha level of .05 using a repeated measures t-test, Wilcoxon, and one-way analysis of variance. The two groups of healthy subjects that participated in balance training did show improvements in one component of unilateral stance and two components of limits of stability. However, statistically, these two groups did not improve significantly more than the control group, which received no training. This may have been due to multiple limitations identified by the researcher. With attention paid to these limitations, this study can be used as a preliminary model that can serve as a vantage point upon which to build future research

Structural Variations Involving s-block Metal Pyrazolates

Alkali and alkaline earth metal organometallics have been sought after for a variety of applications such as in electronic devices produced by novel metal organic chemical vapor deposition precursors, catalysts and as synthetic reagents. Despite significant advances in synthetic techniques, the chemistry of the highly reactive s-block metals is still relatively unexplored. It is difficult to predict properties, structure and binding modes of these compounds due to a number of factors including enhanced reactivity and tendency to aggregation due to the large metal diameter. On the other hand, many of the s-block metals are earth abundant and environmentally friendly, making them highly attractive reagents. The use of bulky ligands has propelled the chemistry of the metals, as the large ligands have a unique capability to suppress aggregation. The use of bulky ligand capable of participating in secondary metal-ligand π (M-π) interactions enables further control of metal coordination environment and has allowed for the synthesis of a variety of novel s-block compounds of low nuclearity, while introducing the capacity of fine-tuning reactivity, a necessary requirement for the use of these compounds for the above mentioned applications. However, not much is know about M-ligand π interactions, as such, their impact is difficult to predict. Early studies suggest a direct dependency on metal size and character. The first part of this work focuses on developing synthetic schemes for the formation of novel heavy alkali metal pyrazolates (pz). Pyrazolates of the lighter alkali metals, lithium and sodium, have been well explored, yet there are no literature examples involving the heavier congeners rubidium or cesium. The second part of this work explores the synthesis and characterization of novel heteroleptic alkaline earth pyrazolate tetraarylborates. This new family of bisarenes of the form [M(thf)2(tBu2pz)(B((3,5-Me2)C6H3)4)] (M= Sr, Ba) reveal the increased tendency of the heavy alkaline earth metals towards M-π interactions, whereas the lighter metals afforded monocationic species of the type [M(thf)2(Et2O)2(tBu2pz)][B((3,5-Me2)C6H3)4] (M = Mg, Ca) where predominant metal-donor interactions, rather than M-ligand π interactions are observed. Furthermore, the use of bulky tBu2pzH ligand reveals how ligand steric demand can be used to circumvent cluster or aggregate formation, which are typically observed when using less sterically hindered systems. In summary, the results presented here provide a seminal understanding on how M-ligand π interactions can be used purposefully to control the structure and thus the function of the heavy s-block metals. This will ultimately help in the construction of highly selective catalysts

Feudal America

Do Americans live in a liberal capitalist society, or a society in which big money, private security, and personal relations determine key social outcomes? Shlapentokh and Woods argue that the answer to these questions cannot be found among the conventional models. Offering a new analytical tool, the authors present a provocative explanation of the nature of contemporary society by comparing its essential characteristics to those of medieval European societies. Their feudal model emphasizes five elements: the weakness of the state to protect its citizens, conflict and collusion between and within organizations that involve corruption and other forms of illegal or semilegal actions, the dominance of personal relations in political and economic life, the prevalence of an elitist ideology, and the use of private agents and organizations to provide safety and security. Feudal America urges readers to look for explanations of contemporary social problems in medieval European history

The Threat of Terrorism and the Changing Public Discourse on Immigration after September 11

This article uses articles from the opinion-leading press to investigate how the news media\u27s repertoire of negative portrayals changed after the September 11 terrorist attacks. It is based on a systematic random sample of 360 articles from two, opinion-leading newspapers---one known for its liberal slant (New York Times) and one known for its conservative slant (Wall Street Journal). The sample is drawn from a large population of articles published over a six-year period (1998-2004). The findings show that the percentage of negative frames involving not only terrorism but also other non-terrorist threats increased significantly after September 11. The elevated frequency of negative frames was found in both the New York Times and the Wall Street Journal, but the increase was significantly greater in the conservative periodical. Immigrants from non-European countries were also significantly more likely to be associated with negative frames than European immigrants. These three variables-national origin, news source, and September 11-were strong predictors of negative frames, even when controlling for other correlates. Suggesting an authoritarian turn in American political discourse, the study highlights cultural factors, as opposed to the conventional psychological explanations, as key determinants of the changing public discussion of immigration after September 11

Feudal America

Do Americans live in a liberal capitalist society, or a society in which big money, private security, and personal relations determine key social outcomes? Shlapentokh and Woods argue that the answer to these questions cannot be found among the conventional models. Offering a new analytical tool, the authors present a provocative explanation of the nature of contemporary society by comparing its essential characteristics to those of medieval European societies. Their feudal model emphasizes five elements: the weakness of the state to protect its citizens, conflict and collusion between and within organizations that involve corruption and other forms of illegal or semilegal actions, the dominance of personal relations in political and economic life, the prevalence of an elitist ideology, and the use of private agents and organizations to provide safety and security. Feudal America urges readers to look for explanations of contemporary social problems in medieval European history

Congressional Hearings: Immigration Frames in Expert Testimonies

This book offers a broad interdisciplinary approach to the changes in the U.S. immigration debate before and after 9/11. A nation’s reaction to foreigners has as much to do with sociology as it does with political science, economics and psychology. Without drawing on this knowledge, our understanding of the immigration debate remains mundane, partial, and imperfect. Therefore, our story accounts for multiple factors, including culture and politics, power, organizations, social psychological processes, and political change. Examining this relationship in the contemporary context requires a lengthy voyage across academic disciplines, a synthesis of seemingly contradictory assumptions, and a grasp of research traditions so vast and confusing that an accurate rendering may seem implausible. And yet, to tell the story of the immigration debate in the age of terrorism, polarization, and Trump in any other way is to tell it in part. The immigration debate in the United States has always been about openness. Two questions in particular—how open should the door be and what type of immigrant should walk through it—have characterized policy disputes for well over a century. In the current debate, expansionists want to see more legal immigrants in the U.S. and greater tolerance, if not respect, for immigrants. Restrictionists favor lower levels of immigration, stronger borders, and tighter law enforcement measures to stop the stream of ‘illegal’ migration and alleged crime. The aim of this book is to describe how these opposing views materialized in the news media, political rhetoric, and, ultimately, in policy. Much of our argument rests on the idea that history matters, that the dominant narrative about immigration is in constant flux, and that the ‘winner’ of the immigration debate is determined by a vector of contextual elements: the joint impact of current events, enduring traditions, and political-economic forces. Our approach to the immigration debate avoids deterministic claims and grand-scale projections. Although we argue with conviction that a climate of fear played an important role in shaping the debate, the fear itself and its effects on social attitudes and public policy were neither inevitable nor necessarily long lasting

Putting false memories into context: The effects of odour contexts on correct and false recall

False memories created by the Deese/Roediger-McDermott (DRM) paradigm are often accompanied by contextual information. Yet, research investigating the effects of context on false memories is surprisingly scarce. We used the context-dependent memory (CDM) model to construct same versus different context conditions using odours as contexts and DRM lists as to-be-remembered stimuli. Experiment 1 showed that levels of correct recall were higher in the same-context condition than in the changed-context condition, but no effects of context were observed in false recall. Experiment 2 used different odours and a longer retention interval and showed that context dependent memory effects were found for both true and false memory. For true memory, context reinstatement improved memory, whilst simultaneously reducing false memory. Theoretical and forensic implications of these findings are discussed