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IDENTIFICATION AND CHARACTERIZATION OF CONTACT SITES BETWEEN HUMAN FOLLICLE STIMULATING HORMONE AND THE FOLLICLE STIMULATING HORMONE RECEPTORSohn, Johann 01 January 2005 (has links)
Follicle stimulating hormone (FSH) comprises an ?? subunit and a ?? subunit,whereas the FSH receptor consists of two halves with distinct functions, the N-terminalextracellular exodomain and C-terminal membrane associated endodomain. FSH initiallybinds to exodomain, and the resulting FSH/exodomain complex modulates the endodomainand generates signal. However, it has been difficult to determine which subunit of FSHcontacts the exodomain or endodomain, and in what orientation FSH interacts with them.To address these crucial issues, the receptor was Ala-scanned and the hormone subunitswere probed with photoaffinity labeling with receptor peptides corresponding to the Nterminalregion of the exodomain and exoloop 3 of the endodomain. The results show thatboth regions of the receptors are important for hormone binding and signal generation. Inaddition, the FSH ?? subunit is specifically labeled with the N-terminal peptide, whereas the?? subunit is labeled with the exoloop 3 peptide. These contrasting results show that the FSH?? subunit is close to the N-terminal region and the ?? subunit is projected toward exoloop 3in the endodomain. The results raise the fundamental question whether the ?? subunit,common among the glycoprotein hormones, plays a major role in generating the hormonesignal common to all glycoprotein hormones.
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COMPREHENSION AND READABILITY OF DRUG INFORMATION: A COMPARATIVE STUDY AT DIFFERENT LEVELS OF READING ABILITY.STRATTON, TIMOTHY PATRICK. January 1986 (has links)
Ley's Partial Model of Compliance suggests that patients who understand information given to them are more likely to remember the information and are more likely to be satisfied with the information. The model then suggests that these components will lead to greater patient compliance with medication regimens. To test the model, Patient Package Inserts (PPIs) describing thiazide diuretics from the American Association of Retired Persons, the American Medical Association, the Canadian Pharmaceutical Association, the Food and Drug Administration, the National Association of Retail Druggists, the United States Pharmacopoeial Convention and a Test PPI written by the Principal Investigator were used. The SMOG Readability Formula was used to determine the grade levels at which PPIs were written. One hundred thirty-six adults enrolled in GED classes in Tucson and other communities and 107 adults enrolled in remedial reading classes at Tucson's Pima Community College were administered the Zip Scale reading placement test and blocked by their reading abilities. Within each of the three blocks, subjects randomly received one of the seven information sheets or no sheet. Subjects took a multiple-choice test based upon information common to all of the PPIs, a cloze comprehension test based upon the PPI which they read, and completed a satisfaction survey which asked subjects to rate the PPI which they read. Subjects also read five vignettes describing fictitious patients taking thiazides who were confronted with different barriers to compliance. Subjects indicated how likely the fictitious patients were to overcome the barriers to compliance. Among this sample of remedial-reading adults, the Test PPI emerged as clearly superior to the others for any of the variables measured. This result would behoove providers of PPIs to rewrite PPIs, reducing the difficulty of these documents as much as possible. Ley's Partial Model of Compliance did not accurately describe the associations between Understanding, Memory, Satisfaction and Compliance for this sample. A New Model emerged describing different associations between these components and between subject reading ability and PPI readability.
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Common Techniques in Graceful Tree Labeling with a New Computational ApproachGuyer, Michael 17 May 2016 (has links)
The graceful tree conjecture was first introduced over 50 years ago, and to this day it remains largely unresolved. Ideas for how to label arbitrary trees have been sparse, and so most work in this area focuses on demonstrating that particular classes of trees are graceful. In my research, I continue this effort and establish the gracefulness of some new tree types using previously developed techniques for constructing graceful trees. Meanwhile, little work has been done on developing computational methods for obtaining graceful labelings, as direct approaches are computationally infeasible for even moderately large trees. With this in mind, I have designed a new computational approach for constructing a graceful labeling for trees with sufficiently many leaves. This approach leverages information about the local structures present in a given tree in order to construct a suitable labeling. It has been shown to work for many small cases and thoughts on how to extend this approach for larger trees are put forth. / McAnulty College and Graduate School of Liberal Arts; / Computational Mathematics / MS; / Thesis;
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Expert label pattern design system and virtual label simulation.January 2007 (has links)
Liu Chung Yan. / Thesis submitted in: September 2006. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 70-74). / Abstracts in English and Chinese. / ABSTRACT --- p.i / ACKNOWLEDGEMENTS --- p.v / TABLE OF CONTENTS --- p.vi / LIST OF FIGURES --- p.viii / Chapter CHAPTER 1. --- INTRODUCTION --- p.1 / Chapter 1.1 --- Woven Label --- p.3 / Chapter 1.2 --- Literature Review --- p.5 / Chapter 1.3 --- Objectives of the Research --- p.7 / Chapter CHAPTER 2. --- EXPERT LABEL PATTERN DESIGN SYSTEM --- p.10 / Chapter 2.1 --- Frame Based Expert System --- p.10 / Chapter 2.2 --- How the System Modify the Label --- p.13 / Chapter 2.3 --- System Operation --- p.15 / Chapter 2.4 --- Software Development - VLabel --- p.16 / Chapter 2.4.1 --- Color Settings for the System --- p.17 / Chapter 2.4.2 --- Generation of Label Template --- p.18 / Chapter 2.4.3 --- Creating New Label from Label Template --- p.20 / Chapter 2.4.4 --- Other Editing Tools --- p.22 / Chapter 2.4.5 --- Font and Edge Library --- p.23 / Chapter 2.5 --- Application Examples of the VLabel software --- p.24 / Chapter CHAPTER 3. --- VIRTUAL LABEL SIMULATION --- p.28 / Chapter 3.1 --- Geometric Modeling of the Label --- p.29 / Chapter 3.1.1 --- Geometric Modeling of Fabric Structure --- p.29 / Chapter 3.1.2 --- Generation of the Geometric Model of the Label --- p.39 / Chapter 3.2 --- Deformation of the Label under the Deformation of Warp Yarns --- p.45 / Chapter 3.2.1 --- Model of a Woven Cell --- p.45 / Chapter 3.2.2 --- Analysis of the Stretched Warp Threads during the Weaving Process … --- p.50 / Chapter 3.2.3 --- Analysis of the Warp Threads during the Relaxing Process --- p.51 / Chapter 3.3 --- Result of the Virtual Label Simulation --- p.52 / Chapter CHAPTER 4 --- CONCLUSIONS --- p.62 / APPENDIX I. DEFINITION OF CLASSES IN EXPERT SYSTEM --- p.63 / APPENDIX II.PUBLICATION LIST --- p.69 / BIBLIOGRAPHY --- p.70
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Mode-of-action of PAF26 and the discovery of more active and stable cyclic PAF26 derivativesZhao, Can January 2017 (has links)
The significance of fungal infections has been grossly underestimated. Only a few drugs are clinically available to treat life-threatening fungal infections, and resistance against these drugs is rising. Antifungal peptides (AFPs) are being actively explored as novel pharmaceuticals. PAF26 is a de novo designed hexapeptide possessing N-terminal cationic and C-terminal hydrophobic regions. Previously the roles of each of these motifs in the antifungal mode-of-action of PAF26 have indicated that it involves three stages: interaction with the plasma membrane, internalisation, and cell killing. The overall aim of my project was to obtain further insights into its mode-of-action and develop more active antifungal derivatives of PAF26. Three experimental fungal systems were used in this study: the model Neurospora crassa, the human pathogen Aspergillus fumigatus and the plant/human pathogen Fusarium oxysporum. The first objective of the study was to evaluate the impact of different fluorescent labels on the intracellular localisation and antifungal properties of PAF26. For this purpose a library of PAF26 labelled with 13 different fluorophores was synthesised. This library contained PAF26 conjugates of broad chemical and spectral diversity. These fluorescent PAF26 conjugates were analysed by live-cell imaging and tested for their antifungal activities. The different fluorescent labels were found to have significant impacts both on intracellular localisation and antifungal activities. TMR, carboxyfluorescein, NBD and DMN were found to be the best labels for live-cell imaging because they had the least influence on the intracellular localisation and antifungal activity of PAF26. The second objective was to identify target proteins of PAF26 in N. crassa cells. A large number of proteins were identified as binding to PAF26 from a protein pull-down and mass spectroscopy analysis using TMR- and fluorescein-labelled PAF26. One of these proteins was the highly abundant plasma membrane ATPase PMA-1. An in-silico analysis showed that PMA-1 is likely to be a major target protein of PAF26. The final objective was to develop novel antifungals based on PAF26 with improved activities and stability. Novel cyclic derivatives of PAF26 were designed in-silico against PMA-1. These peptides were synthesised and tested against N. crassa, A. fumigatus and F. oxysporum and were found to have higher activities (at the sub-micromolar level) and greater stability than the linear PAF26. Overall this study has provided novel mechanistic insights into the mode-of-action of PAF26 and discovered novel highly active antifungal peptides with clinical potential as therapeutics.
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Distance Effects in Similarity Based Free CategorizationMiller, Benjamin Alan 01 September 2015 (has links)
This experiment investigated the processes underlying similarity-based free categorization. Of particular interest was how temporal distance between similar objects affects the likelihood that people will put them into the same novel category. Participants engaged in a free categorization task referred to as binomial labeling. This task required participants to generate a two-part label (A1, B1, C1, etc.) indicating family (superordinate) and species (subordinate) levels of categorization for each object in a visual display. Participants were shown the objects one at a time in a sequential presentation; after labeling each object, they were asked to describe the similarity between that object and previous objects by selecting one of five choices from a drop down menu. Our main prediction was that temporal distance should affect categorization, specifically, that people should be less likely to give two identical objects the same category label the farther apart they are shown in the display. The primary question being addressed in this study was whether the effects of distance are due to a decreased likelihood of remembering the first object when labeling the second (what we refer to as a stage 1 or sampling effect) or to factors during the actual comparison itself (a stage 2 or decision effect)? Our results showed a significant effect of distance on both the likelihood of giving identical objects the same label as well as on the likelihood of mentioning the first object when labeling the second object in an identical pair. Specifically, as the distance between two identical objects increased, the likelihood of giving them the same label, as well as mentioning their similarity, both decreased. Importantly, the decreased probability of giving the second object the same label seemed entirely due to the decreased probability of remembering (sampling) the first object, as indicated by the menu responses. These results provide strong support for the idea that the effect of temporal distance on free categorization is mainly due to stage 1 factors, specifically to its effect on the availability of the first instance in memory when labeling the second. No strong evidence was found in this experiment supporting a separate distance effect at the comparison-decision stage (i.e., stage 2).
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A fluorescent labelling technique to detect changes in the thiol redox state of proteins following mild oxidative stressLui, James Kwok Ching January 2008 (has links)
There is increasing evidence that hydrogen peroxide (H2O2) can act as a signalling molecule capable of modulating a variety of biochemical and genetic systems. Using Jurkat T-lymphocytes, this study initially investigated the involvement of H2O2 in the activation of a specific signalling protein extracellular signal-regulated protein kinase (ERK). It was found that as a result of H2O2 treatment, mitochondrial complex activities decreased which led to subsequent increase of mitochondrial reactive oxygen species (ROS) production. The increase of ROS resulted in higher cellular H2O2 as well as increased ERK activation. This study demonstrated that in an oxidative stress setting, H2O2 production from the mitochondria was an essential component in maintaining the activation of a signalling protein. One way in which H2O2 could influence protein function is by the oxidation of susceptible thiol groups of cysteine residues. To further understand the variety of signalling pathways that H2O2 may be involved in, an improved proteomics technique was developed to globally identify proteins with susceptible thiol groups. The
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The effects of labeling and stereotype threat on offender reintegrationBreen, Amanda Hilary 01 May 2011 (has links)
After their release from prison, offenders are faced with many hardships that hinder their reintegration efforts. Often, offenders are stereotyped and face community exclusion due to their criminal record. Much of the literature on reintegration has focused on the way in which society stereotypes offenders, but not how offenders interpret and internalize these stereotypes. This study examines the way offenders internalize the stereotypes associated with having a criminal record, and how this affects their reintegration. Data was gathered by conducting 18 in-depth interviews with offenders at the John Howard Society in Toronto. The interviews showed that all participants felt that they had been negatively labeled by others based on the fact that they have a criminal record and/or spent time in prison. Additionally, five participants indicated experiencing stereotype threat, and believed this phenomenon to have had a negative impact on their ability to reintegrate back into society. / UOIT
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Study of Cyanine Dye Binding to Amino Acids and Its Analytical UtilityMerid, Yonathan 29 April 2010 (has links)
Investigation of the NIR cyanine dye MHI-36 shows binding affinity to charged amino acids. This cyanine dye showed aggregation and dimer formation at higher dye concentration (2.0x10-3 M) induced by lysine. When dye concentration decreased to 1.0x10-4M no strong aggregate formation was viewed. Dye shows strong binding and selectivity properties towards charged amino acids lysine and arginine, compared to neutral leucine. It’s believed the positively charged presence was able to break and disrupt the conjugated π- π bonds at lower dye concentration. Computational work showed intramolecular aggregation of the phenyl groups on the dye. These aggregates are believed to create electron rich environment suitable for lysine interaction.
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IDENTIFICATION AND CHARACTERIZATION OF CONTACT SITES BETWEEN HUMAN CHORIONIC GONADOTROPIN AND THE AMINO TERMINAL REGION OF THE LUTEINIZING HORMONE/CHORIOGONADOTROPIN RECEPTORMcCaffrey, Rebecca 01 January 2002 (has links)
The luteinizing hormone / choriogonadotropin receptor (LH/CG-R) is a member of theG protein-coupled receptor family. The LH/CG-R has seven transmembrane helices, threeexoloops, three cytoloops, a C-terminal tail, and an extensive N-terminal exodomain. Theexodomain is capable of binding hormone with high affinity without hormone action. Previousstudies have shown that the amino-terminal region of the LH/CG receptor contacts both subunitsof human chorionic gonadotropin (hCG). In particular, three residues (Leu20, Cys22, and Gly24)were found to be crucial for hormone binding. In this thesis work, benzoylphenylalanine (Bpa),a photoactivatable reagent, was used to continue investigating the interactions of the N-terminalregion of the LH/CG-R with hCG. Bpa has been directly incorporated at a defined position intopeptides representing amino acids 17-36 of the LH/CG-R. These peptides were radiolabeledwith 125I and used in photoaffinity labeling studies to identify and characterize the contact site(s)between the N-terminal region of the LH/CG-R and hCG. Results suggest that Cys22 is theprimary contact residue in this region. Peptide and hormone concentration dependent as well asUV duration dependent photoaffinity labeling experiments confirm that the photolabeling ofhCG by hLHR17-36(C22Bpa) is specific. Competition of labeling studies indicate that the hLHR17-36(C22Bpa) peptide is a good mimic of the wild type N-terminal portion of the receptor. In-geldigestions of photolabeled hCG ?? and photolabeled hCG ?? with CNBr indicate that the Nterminalregions of both hCG ?? and hCG ?? were photoaffinity labeled by hLHR17-36(C22Bpa).Based on the fact that the N-terminal regions of each subunit are located on the convex side ofthe heterodimer, these results provide evidence that the N-terminal portion of the receptor wrapsaround the back of hCG, contacting the convex face of the hormone.
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