12230 research outputs found
Sort by
Overcoming Challenges in Chemical Glycosylation to Achieve Innovative Vaccine Adjuvants Possessing Enhanced TLR4 Activity
Lipopolysaccharide (LPS) mimicry leading to toll-like receptor 4 (TLR4) active compounds has been so far based mainly on reproducing the lipid A portion of LPS. Our work led to a series of structurally simplified synthetic TLR4 agonists in preclinical development as vaccine adjuvants called FPs. FPs bind MD2/TLR4 similarly to lipid A, inserting the lipid chains in the MD2 lipophilic cavity. A strategy to improve FPs’ target affinity is introducing a monosaccharide unit in C6, mimicking the first sugar of the LPS core. We therefore designed a panel of FP derivatives bearing different monosaccharides in C6. We report here the synthesis and optimization of FPs’ C6 glycosylation, which presented unique challenges and limitations. The biological activity of glycosylated FP compounds was preliminarily assessed in vitro in HEK-Blue cells. The new molecules showed a higher potency in stimulating TLR4 activation when compared to the parent molecule while maintaining TLR4 selectivity
Phylogeny and Taxonomy of Genus Physaria in North America
Physaria is a genus of ~108 species belonging to family Brassicaceae that is predominantly distributed in Western North America, but one species occurs in Arctic Russia and Northern Canada and several species occur in South America. Regardless of the vast number of species in the genus, the genus lacks a well-resolved phylogeny representing many taxa, partially because phylogeny reconstruction is complicated by the fact that many species of Physaria vary in chromosome numbers and ploidy levels. In chapter 1, we review how polyploids are formed and become established and summarize what is known about variation in chromosome number and ploidy in Brassicaceae and in the genus Physaria. In Chapter 2, we extracted DNA representing 84 species of Physaria species and employed a 2b-RAD sequencing technique to generate data for phylogeny reconstruction. The specific goals of the study were 1) to reconstruct the phylogeny of Physaria and assess whether species relationships proposed in early monographs by Payson (1921) and Rollins and Shaw (1973) based on morphology correspond to the current species relationships revealed through the molecular phylogeny representing 86 species of Physaria, 2) to investigate the monophyly of species represented by multiple accessions in the resulting phylogeny, and 3) to investigate how the inclusion of polyploid taxa affects the topology of the phylogeny, which may help shed light on the origins of polyploid taxa. The resulting phylogeny had species from Mexico and Texas at the base of the tree, suggesting that the genus originated in southern North America, although additional outgroups and a formal biogeographic analysis are needed to confirm this result. The species in the phylogeny were grouped into two main clades, one containing species predominantly from eastern North America, and one containing species predominantly from western North America. Except for the group 1 species proposed by Rollins and Shaw in 1973, none of proposed groups of species in monographs formed clades. Instead, the resulting phylogeny grouped species collected from nearby locations irrespective of their taxonomic placement, suggesting a strong biogeographical affinity towards species groupings, possibly due to hybridization within geographic locations. Only a handful of species were monophyletic; in the eastern clade, P. recurvata, P. gracilis, P. angustifolia, P. globosa, and a new species, P. ouachitensisformed monophyletic species in phylogenies in which the polyploid species were present and absent. In the western clade, P. brassicoides, P. pruinosa, P. valida, P. parvula, P. pulvinata and P. intermedia formed monophyletic species when the polyploids were removed. The topology varied depending on whether polyploids were included, suggesting that some species may be hybrids or allopolyploids. Conducting additional chromosome counts, identifying hybrid and allopolyploid taxa, and reconstructing the evolution of ploidy levels is an important area for future studies to understand how they have affected diversification in the group. Overall, the current study resulted a well resolved phylogeny with many taxa of Physaria, which is useful for future studies on understanding the evolutionary history, character evolution, and biogeography of the genus
K-12 Teachers’ Retention of Arts Integrated Professional Development
Arts integration is an interdisciplinary teaching model in which the arts become a conduit for the contextualization and understanding of non-arts content. Research has shown this approach increases academic engagement and content retention (Rinne et al., 2011). The use of arts integration also provides gains for teachers. Teachers perceive their practice more innovative and better able to reach the needs of diverse learners (Bellisario & Donovan, 2012). For the benefits of arts integrated learning to be achieved, teachers must acquire the knowledge and techniques of this teaching model. This requires knowledge in both arts content as well as the pedagogical strategies of the instructional model. Professional development (PD) is often how this learning is disseminated (Saraniero et al., 2018). Understanding what information is retained from these PD experiences may help provide a foundation to design subsequent training. A mixed-methods research design was utilized to discover to what extent learning from a prior arts integrated PD was retained by K-12 classroom teachers. Instruments used were a 5-point Likert survey and in-depth interviews. Retention from the PD was examined using Knowles’ Six Assumptions of Andragogy (1980). Results showed an increase in teachers’ understanding and implementation of the arts integration teaching model. Confidence and use of visual arts strategies were reported at higher levels than other art forms. Teachers identified a need for continued support after the PD to help with implementation of arts integration into their teaching practice
Student Movements, Politics, and Policy in Chile, 2001 – 2012
Chile has frequently been touted as an economic miracle, the “Jaguar of Latin America”. Boasting the strongest economy in South America, due to severe neoliberal economic structural adjustments made under the dictatorship of General Augusto Pinochet, it has long been held up as the perfect exemplar of economic growth and stability, as well as the poster child for the effectiveness of neoliberal economics. After the re-establishment of democracy in 1990, political conditions improved as well; the country enjoyed a decade of stability and peace under its first two democratically-elected governments.
Yet, beginning approximately ten years after the transition to democracy, Chilean students began engaging in massive waves of protest. Discontent grew, and students manifested in larger numbers and for longer periods of time with each successive cycle of mobilization, eventually culminating in the “social explosion” of 2019. This dissertation examines three cycles of student mobilization in Chile; the Mochilazo (2001), the Revolución Pengüina (2006), and the Invierno Chileno (2011), seeking to explain the effects the protests had on public policy, laws, and political institutions in the country. It delves into how the students were able to enlarge both the number of participants and their claims with each successive cycle; their repertoires of contention; their interactions with government officials; their framing and messages; and what changes occurred as a result of each cycle. A combination of the joint-effect model and Felix Kolb’s framework are used to analyze the effects of social mobilization.
Guided by the state-movement intersection model, Marco Giugni’s joint-effect model, and Felix Kolb’s framework for analyzing the impact of social movements, I find that the students were able to affect numerous changes in each cycle of mobilization, enlarging their claims and numbers each time via transferred knowledge from previous cycles. Chilean students have come to be regarded as important political actors in the political system, and have evolved their claims to demand massive structural changes to both the political and economic systems in the country
High-Resolution Spectroscopy of Interstellar Lines and Comets
The study of interstellar molecules such as CO is crucial because interstellar ices in the core of a pre-solar molecular cloud provide the starting point for volatile evolution in the protoplanetary disk. A record of the initial volatile composition of the protoplanetary disk can be obtained from the study of the chemical composition of cometary nuclei. Because of their long residence in the Oort cloud and infrequent passage through the inner solar system, long-period comets are one of the most primitive bodies in our solar system that can tell us about the composition of the early solar system. High-resolution infrared spectroscopy allows for measuring the chemical abundances of primary volatile species (sublimed native ices directly from the nucleus) in the comae of comets, which are crucial for their chemical taxonomic classification. Characterizing the chemical composition of comets over a range of heliocentric distances (Rh) is crucial to investigate whether the composition of the cometary nucleus varies with heliocentric distance or remains constant. There is a systematic enhancement of some molecules (C2H2, NH3, H2CO) for comets observed close to the Sun compared to those observed beyond ~1 AU. Measurements of the chemical abundance of primary volatile species in the long-period comet C/2020 S3 (Erasmus) observed near Rh ~ 0.5 AU, presented in this study, contribute to the effort of investigating the chemical abundances at small heliocentric distances. Within 2 AU from the Sun, cometary activity is mainly driven by the sublimation of H2O ice. On the other hand, cometary outgassing beyond the sublimation region of H2O (~ 3.0 AU) is driven by hypervolatile species such as CO and CO2. There have only been a few comet measurements made over the transitional heliocentric distance range Rh ~ 2.5-3.0 AU because the majority of comets are either very faint or show low activity at this distance from the Sun. This leaves it uncertain where the transition from hypervolatile to H2O-driven activity occurs. Observations of long-period comet C/2017 K2 (Pan-STARRS) spanning a range of Rh ~2.35 - 3.15 AU were conducted to address this critical topic in cometary science
Design Thinking’s Effect on Empathy Development in Middle School English- Language Arts
The purpose of this quantitative study was to explore the impact of Design Thinking on students\u27 empathy development in middle school English Language Arts (ELA) classrooms. The study involved two middle school instructors with eight classes, implementing Design Thinking, Reader\u27s Workshop, and traditional ELA curriculum in different combinations (n =102) and two control classes (n =27).
The Adolescent Empathy Measure (AMES) and rubrics for analyzing student writing samples were used to assess changes in empathy. The AMES was given before and after the interventions, and the writing samples were analyzed before and after the interventions as well. The findings indicate partial support for the hypotheses related to cognitive empathy but no statistically significant results for affective empathy. The study contributes to the understanding of Design Thinking\u27s potential in enhancing empathy and suggests the need for further research in this area. Limitations and implications for future studies are discussed, emphasizing the role of Design Thinking in education and its potential to address the social and emotional needs of students in a post-pandemic educational landscape
Successfully Scaling Digital Technology Ventures: An Empirical Study of the Strategic Choices that Maximize Firm Value
Our study aims to understand the choices managers working for subscription-based digital ventures must make at arguably the most critical juncture of their firm’s lifecycle. With few slack resources to repair mistakes, managers at these scaling firms must make decisions that are larger in scope and scale than in the start-up phase. Tradeoffs are often required as decision-makers face choices such as investing more resources in sales and marketing to drive growth or in product development to improve quality and add new products or features. In many instances, the question is whether to forego some growth opportunities to maximize profitability or pursue growth even if the result is profit losses. Prioritization must be given to a few limited resources while consciously allowing others to remain underfunded. Further complicating matters, these initial investments are often inefficient. For example, a new sales team does not instantly create value. Managers making poor choices with minimal financial slack heighten a scaling firm\u27s risk of setback or failure. Using resource orchestration as the theoretical framework, we conduct a panel analysis over a six-year period and discuss the empirical implications of the resource configuration strategies managers can implement to positively impact the firm valuation of scaling digital ventures. We find that managers who navigate the tradeoff between value creation and value capture in a way that meets the rule of 40, while also delivering future growth that includes a mix of foreign sales with a business-to-business revenue models will significantly impact firm value
Not All Best Practices Result in Best Performances: Two Empirical Studies of Online Accounting Education
Exploring the impact of specific pedagogical strategies in online accounting education on student learning outcomes is central to this research. This two-study dissertation focuses on the influence of course delivery methods on student performance and the mediating function of accounting efficacy. A diverse sample of accounting and business students was quantitatively analyzed to determine the relationship between course structure, classroom justice, students’ motivation and their accounting efficacy, applicability of learned material, and final grades. Even though certain teaching practices were advantageous, the combination of these practices did not always lead to improved student performance, according to the findings. Significant determinants of student learning outcomes were found to be course structure, classroom justice, and accounting efficacy, with accounting efficacy playing a pivotal mediating role on the impact of applicable learned material. The results of this research highlight the multifaceted character of accounting education and the significance of structured teaching methods centered on effectiveness and makes a substantial contribution to the academic discourse of accounting education by providing educators, institutions, and policymakers with crucial insights
Assessing Threats to Plant Populations: Linking Pollinator Differences to Patterns of Plant Fitness and Population Genetics
Land use change is a major driver of biodiversity loss and consequently has led to the loss of genetic diversity in many plant populations due to declines in population sizes and an increase in spatial isolation. However, not all plant populations respond similarly to land-use change, suggesting there are additional mechanisms mediating plant population genetic patterns. Here, I examine the role of pollinators as this mediating factor. In Chapter 1 I conducted a meta-analysis to investigate how different types of pollinators drive changes in gene flow for plant populations in disturbed habitats, finding that different types of pollinators mediate different levels of genetic connectivity in plant populations and that pollinators like large bees are tolerant of disturbance, maintaining equal levels of gene flow in undisturbed and disturbed habitats. In Chapter 2 I studied the relationship between landscape and habitat characteristics, pollinator community, and plant mating quality using the generalist pollination system of Campanula americana. I found that different types of pollinators respond to different aspects of the environment and differentially affect mating quality. In Chapter 3 I investigated the consequences of differences between pollinators in their pollen deposition patterns. I tested if pollination by multiple donors selects for offspring with higher fitness in Allium stellatum and found that pollen loads with a greater number of donors increased female reproductive success at the expense of slower growing seedlings. This dissertation has illuminated the intricate role pollinators play in influencing plant population dynamics and their importance in plant conservation
High Resolution Intracavity Laser Absorption Spectroscopy of Transition Metal-containing Diatomic Molecules
Three transition metal-containing diatomic molecules have been studied using intracavity laser spectroscopy. Many of the transitions were recorded using a Fourier-transform spectrometer for detection, allowing collection at Doppler-limited resolution for the gas phase molecules. Several vibrational bands in two electronic transition systems of tantalum fluoride (TaF) have been analyzed, and new molecular constants provided. Transitions involving six electronic states of tungsten sulfide (WS) have been analyzed, with new and updated constants provided, including a deperturbation analysis of three vibrational bands in two of the states. Finally, a fresh perspective on two electronic states of tungsten oxide (WO) included a deperturbation analysis to support decades of speculation regarding the nature of the two interacting states