Increasing Breast and Cervical Cancer Screenings in Somali Women through Community Education

Paper approved May 2019 by the faculty of UMKC in partial fulfillment of the degree of Doctor of Nursing PracticeApproved May 2019 by the faculty of UMKC in partial fulfillment of the requirements for the degree of Doctor of Nursing PracticeDespite best practice guidelines, Somali refugee women access breast and cervical cancer screenings at a significantly lower rate than other women in the United States. This doctoral nursing project evaluated the effectiveness of an evidence-based community education program to increase breast and cervical cancer screenings among Somali refugee women. This pilot quasi experimental project incorporated culturally tailored education, community health workers, and facilitated screening access in a community setting with the goal of increasing adherence to current cancer screening guidelines in collaboration with a free community health clinic. Twenty Somali women aged 21-74 attended three educational sessions, and 11 attendees consented to provide demographic data, history of Pap testing and/or mammography screening, and intention to receive screening if under or never screened. Primary outcomes included receipt of mammography or Papanicolau testing, and a secondary outcome included intention to receive screening. There was no significant difference pre- and post-intervention for either screening uptake or intention to receive screening. Additionally, the student investigator trained three Somali community health workers to facilitate the education program and collected their written feedback following project completion. This project sought to improve breast and cervical cancer screening adherence and reduce cancer morbidity and mortality in a Somali refugee population in Kansas City, Missouri

Stabilization of peptides by site-specific incorporation of fluorinated amino acids: Model studies and the development of fluorinated, peptide-based HIV-1 fusion inhibitors

The modification of peptides and proteins using side-chain fluorinated amino acids is a widely used strategy to modulate their biophysical and pharmaceutical properties. Systematic investigations can provide valuable insights into the behavior of these non-canonical amino acids in natural protein environments. To this end, the research conducted in this doctoral thesis made use of two well established model systems to evaluate the impact on coiled-coil structure and stability, and proteolytic stability of single substitutions with sterically demanding and highly fluorinated amino acids. First, the incorporation of hexafluoroleucine and two trifluorovaline stereoisomers at two different positions of the hydrophobic core of a parallel heterodimeric coiled-coil model system showed that these amino acids are readily accommodated into stable dimeric α-helical bundles. Remarkably, the single substitution of leucine with hexafluoroleucine leads to a significant increase in thermal stability due to its greater hydrophobicity and efficient packing. Second, fluorinated leucine and isoleucine derivatives in some cases improve the resistance of a model peptide towards different proteases; however, fluorine’s impact cannot be generalized as destabilization was also observed for certain sequences. This might be explained by specific interactions between the fluorinated residues and the respective enzyme binding sites. Noteworthy is that trifluoroisoleucine is able to significantly protect peptides from proteolysis by all tested enzymes when positioned N-terminal to the cleavage site. Finally, studies were carried out towards developing stable, fluorinated peptide based HIV-1 fusion inhibitors. Envelope protein subunit gp41 plays a key role in host cell infection due to the formation of a six-helical bundle consisting of three N-terminal (NHR) and three C-terminal heptad repeat (CHR) sequences. By generating synthetic, judiciously fluorinated CHR-analogues bundle formation and, therefore, cell entry may be inhibited. The previously designed CHR-derived peptide C31 serves as starting point for single substitutions with difluoroethylglycine, trifluoroisoleucine or hexafluoroleucine at a position crucial for helix bundle formation. The resulting fluorinated C31 peptides indeed undergo helix bundle formation with an NHR-peptide, but the resulting complexes exhibit decreased thermal stabilities. Although binding is entropically disfavored, the large negative enthalpy enables a spontaneous binding process. Two of the fluorinated analogues exhibit even higher binding affinities to the NHR-region compared to the native, non-fluorinated parent. Moreover, a hetero-tetrameric scaffold was synthesized that enables a trimeric oligomerization of the NHR-derived segment and will be applied in surface plasmon resonance experiments for a more detailed analysis of the kinetic parameters underlying helical assembly. The results of this thesis will contribute to the rational application of fluorinated amino acids to the development of stable, peptide-based drug candidates.Die Modifikation von Peptiden und Proteinen mit Seitenketten-fluorierten Aminosäuren ist eine weit verbreitete Strategie um biophysikalische und pharmazeutische Eigenschaften dieser anzupassen. Systematische Untersuchungen können dabei wertvolle Einsichten in das Verhalten dieser nicht-kanonischen Aminosäuren in natürlichen Proteinumgebungen liefern. Dazu werden in dieser Doktorarbeit zwei bewährte Modellsysteme genutzt, um den Einfluss einfacher Substitutionen mit sterisch anspruchsvollen und hoch-fluorierten Aminosäuren auf die coiled-coil Struktur und Stabilität sowie auf die Stabilität gegenüber Proteasen zu beurteilen. Zunächst zeigte der Einbau von Hexafluoroleucin und zwei Trifluorovalin-Diastereoisomeren an zwei verschiedenen Positionen im hydrophoben Kern eines parallelen, heterodimeren coiled-coil Modellsystems, dass diese Aminosäuren problemlos in stabilen, dimeren α-helikalen Bündeln akzeptiert werden. Die einfache Substitution von Leucin mit Hexafluoroleucin führt zu einem deutlichen Anstieg der thermischen Stabilität, bedingt durch die größere Hydrophobie und effiziente Packung. Zweitens verbessern fluorierte Leucin- und Isoleucin-Derivate in einigen Fällen die Resistenz eines Modellpeptides gegenüber verschiedenen Proteasen. Der Einfluss von Fluor kann jedoch nicht verallgemeinert werden, da ebenfalls Destabilisierungen für bestimmte Sequenzen beobachtet wurden. Dies könnte durch spezifische Wechselwirkungen zwischen den fluorierten Resten und den entsprechenden Enzymbindungstaschen erklärt werden. Bemerkenswert ist, dass Trifluoroisoleucin die Peptide gegen die Proteolyse durch alle getesteten Enzyme deutlich schützen kann, wenn es N-terminal zur Spaltstelle positioniert wird. Schließlich wurden Studien zur Entwicklung stabiler, fluorierter, peptid-basierter HIV-1 Fusionsinhibitoren durchgeführt. Die Hüllproteinuntereinheit gp41 spielt eine Schlüsselrolle in der Infektion der Wirtszelle durch die Ausbildung eines Sechs-Helix-Bündels, welches aus drei N-terminalen (NHR) und drei C-terminalen Heptad Repeat (CHR) Sequenzen besteht. Mit der Erzeugung von synthetischen, fluorierten CHR-Analoga kann die Bündelbildung und damit der Zelleintritt verhindert werden. Das zuvor konzipierte, aus CHR-abgeleitete Peptid C31 dient hier als Startpunkt für rationale Substitutionen mit Difluoroethylglycin, Trifluoroisoleucin oder Hexafluoroleucin an einer Position, die wichtig für die helikale Bündelbildung ist. In der Tat bilden die daraus resultierenden fluorierten C31 Peptide helikale Bündel mit einem NHR-Peptid aus, allerdings zeigten die entstandenen Komplexe eine verringerte thermische Stabilität. Obwohl die Bindung entropisch nicht begünstigt ist, ermöglicht die hohe negative Enthalpie einen spontanen Bindungsprozess. Zwei der fluorierten Analoga weisen sogar eine höhere Bindungsaffinität zur NHR-Region im Vergleich zum nativen, nicht fluorierten System auf. Zudem wurde ein hetero-tetrameres Gerüst synthetisiert, welches eine trimere Oligomerisierung des NHR-Segmentes ermöglicht und für eine genauere Analyse der kinetischen Parameter der Helixbildung mittels Oberflächenplasmonenresonanzspektroskopie genutzt werden soll. Die Ergebnisse dieser Arbeit tragen so zu einer rationalen Anwendung fluorierter Aminosäuren bei der Entwicklung stabiler, peptid-basierter Wirkstoffkandidaten bei

Design, construction and commissioning of a high-flow radon removal system for XENONnT

A high-flow radon removal system based on cryogenic distillation was developed and constructed to reduce radon-induced backgrounds in liquid xenon detectors for rare event searches such as XENONnT. A continuous purification of the XENONnT liquid xenon inventory of 8.4 tonnes at process flows up to 71 kg/h (200 slpm) is required to achieve a radon reduction by a factor two for radon sources inside the detector. To reach such high flows, the distillation column's design features liquid xenon inlet and outlets along with novel custom-made bath-type heat exchangers with high liquefaction capabilities. The distillation process was designed using a modification of the McCabe-Thiele approach without a bottom product extraction. The thermodynamic concept is based on a Clausius-Rankine cooling cycle with phase-changing medium, in this case the xenon itself. To drastically reduce the external cooling power requirements, an energy efficient heat pump concept was developed applying a custom-made four cylinder magnetically-coupled piston pump as compressor. The distillation system was operated at thermodynamically stable conditions at a process flow of (91$\pm$2) kg/h ((258$\pm$6) slpm), 30 % over design. With this flow, a $^{222}$Rn activity concentration <1 $\mu$Bq/kg is expected inside the XENONnT detector given the measured radon source distribution

Mathematiktreiben und Reflektieren. Entdecken dokumentieren, um neu zu entdecken

Das reziprok aufeinander bezogene Handeln und Dokumentieren eröffnet vielfältige Entdeckungs- und Reflexionsmöglichkeiten für substanzielles Mathematiklernen in der Elementar- und Primarbildung. Hierzu bietet der sogenannte Spiel- und Dokumenten-Raum Möglichkeiten zum aktiv entdeckenden Mathematiktreiben und zur Reflexion in and on action. Welche Entdeckungs- und Reflexionswirklichkeiten wie in individuellen Lernverläufen in reziprok designten Lernumgebungen entwickelt werden, dies wird in einer qualitativen Studie rekonstruiert und modelltheoretisch analysiert. (DIPF/Orig.

Perfect social media image posts: symmetry and contrast influence consumer response

Purpose: Two studies investigate how different structural properties of images – symmetry (vertical and horizontal) and image contrast – affect social media marketing outcomes of consumer liking and engagement. Design/methodology/approach: In Study 1’s experiment, 361 participants responded to social media marketing images that varied in vertical or horizontal symmetry and level of image contrast. Study 2 analyzes field data on 610 Instagram posts. Findings: Study 1 demonstrates that vertical or horizontal symmetry and high image contrast increase consumer liking of social media marketing images, and that processing fluency and aesthetic response mediate these relationships. Study 2 reveals that symmetry and high image contrast improve consumer engagement on social media (number of “likes” and comments). Research limitations/implications: These studies extend theory regarding processing fluency’s and aesthetic response’s roles in consumer outcomes within social media marketing. Image posts’ structural properties affect processing fluency and aesthetic response without altering brand information or advertising content. Practical implications: Because consumer liking of marketing communications (e.g. social media posts) predicts persuasion and sales, results should help marketers design more effective posts and achieve brand-building and behavioral objectives. Based on the results, marketers are urged to consider the processing fluency and aesthetic response associated with any image developed for social media marketing. Originality/value: Addressing the lack of empirical investigations in the existing literature, the reported studies demonstrate that effects of symmetry and image contrast in generating liking are driven by processing fluency and aesthetic response. Additionally, these studies establish novel effects of images’ structural properties on consumer engagement with brand-based social media marketing communications

Cryogenic bath-type heat exchangers for ultra-pure noble gas applications

Two cryogenic bath-type heat exchangers for ultra-pure noble gas applications were developed with particular emphasis on noble gas liquefaction in cryogenic distillation systems. The main objective was to construct heat exchangers for xenon from materials that do not emanate radon and that fulfill ultra-high vacuum standards. Therefore, only high-quality copper and stainless steel materials were used. Especially, large-area oxygen-free copper fins with high conductivity in a new design ensure efficient heat transfer. One bath-type Xe-Xe heat exchanger was designed with a diameter of 50 cm to achieve a xenon condensing capacity of at least 100 kg/h. In order to guarantee the necessary heat transfer between the two xenon reservoirs, this heat exchanger features a specially manufactured stainless steel flange with a copper plate welded inside. We first tested our concept on a dedicated bath-type heat exchanger with a reduced diameter of 30 cm using liquid nitrogen to liquefy the xenon. A model based on conservative assumptions such as film boiling on the nitrogen side and film condensation on the xenon side was developed and applied to caluclate the expected heat transfer for our design. We were able to demonstrate an adjustable xenon liquefaction rate of up to 113 kg/h limited only by our measurement procedure at a cooling efficiency of (0.98 ± 0.03) for the LN$_{2}$-Xe heat exchanger