Lancifodilactone G : insights about an unusually stable enol

From quantum mechanics calculations we confirm that the naturally occurring enol lancifodilactone G is stable over the keto form (by 2.6 kcal/mol in water), the only known stable aliphatic enol (devoid of conjugated or bulky aromatics and lacking a 1,3-diketone structural motif known to stabilize enols). We determine architectural elements responsible for the enol stabilization and find a mechanism for keto-enol conversion in solution. In addition, we correct previously reported computational results that were performed on the misinterpreted structure demonstrating that the enol form of this natural product is more stable than previously thought

Allosteric modulation of DNA by small molecules

Many human diseases are caused by dysregulated gene expression. The oversupply of transcription factors may be required for the growth and metastatic behavior of human cancers. Cell permeable small molecules that can be programmed to disrupt transcription factor-DNA interfaces could silence aberrant gene expression pathways. Pyrrole-imidazole polyamides are DNA minor-groove binding molecules that are programmable for a large repertoire of DNA motifs. A high resolution X-ray crystal structure of an 8-ring cyclic Py/Im polyamide bound to the central 6 bp of the sequence d(5′-CCAGGCCTGG-3′)2 reveals a 4 Å widening of the minor groove and compression of the major groove along with a >18 ° bend in the helix axis toward the major groove. This allosteric perturbation of the DNA helix provides a molecular basis for disruption of transcription factor-DNA interfaces by small molecules, a minimum step in chemical control of gene networks

Lessons Learned from Efforts at Institutional Change: Case Studies of Six OCEPT Institutions

As one part of a multifaceted evaluation of the Oregon Collaborative for Excellence in the Preparation of Teachers (OCEPT), a case study approach was used to enable a deeper understanding of how a diverse group of six institutions attempted to achieve OCEPT goals and to learn more about factors that facilitated or hindered their efforts. Multiple sources of data were used, with heavy reliance on a series of on-site interviews. The analytical framework included a depth and pervasiveness typology of institutional change and a view of change as encompassing meaning, organization, and effects. While goals and accomplishment levels, as well as the depth and pervasiveness of change. varied across the six institutions, OCEPT-influenced changes most likely to be sustained included: new kinds and levels of faculty collaboration; peer-led teaching and learning approaches, and attention to evidence that these approaches positively affect student course performance; increased faculty awareness of their role in teacher recruitment, with related changes in classroom practices; and, continued strengthening of access to infomiation and academic advising for those preparing to become teachers. These institutions, however, did not make significant progress on one major goal of the project—to increase the numbers of underrepresented groups interested in teaching careers. Change was affected by the compatibility of OCEPT goals with institutional and faculty culture, as well as by local collaborative leadership, the size and complexity of the institution, the presence of boundary spanners, and how OCEPT resources were used

Solution-phase synthesis of pyrrole-imidazole polyamides

Pyrrole−imidazole polyamides are DNA-binding molecules that are programmable for a large repertoire of DNA sequences. Typical syntheses of this class of heterocyclic oligomers rely on solid-phase methods. Solid-phase methodologies offer rapid assembly on a micromole scale sufficient for biophysical characterizations and cell culture studies. In order to produce gram-scale quantities necessary for efficacy studies in animals, polyamides must be readily synthesized in solution. An 8-ring hairpin polyamide 1, which targets the DNA sequence 5′-WGWWCW-3′, was chosen for our synthesis studies as this oligomer exhibits androgen receptor antagonism in cell culture models of prostate cancer. A convergent solution-phase synthesis of 1 from a small set of commercially available building blocks is presented which highlights principles for preparing gram quantities of pyrrole−imidazole oligomers with minimal chromatography

Oligomerization Route to Py-Im Polyamide Macrocycles

Cyclic eight-ring pyrrole−imidazole polyamides are sequence-specific DNA-binding small molecules that are cell permeable and can regulate endogenous gene expression. Syntheses of cyclic polyamides have been achieved by solid-phase and solution-phase methods. A rapid solution-phase oligomerization approach to eight-ring symmetrical cyclic polyamides yields 12- and 16-membered macrocycles as well. A preference for DNA binding by the 8- and 16-membered oligomers was observed over the 12-ring macrocycle, which we attributed to a conformational constraint not present in the smaller and larger systems

Morphometric quantification of cockpit karst in a Jamaican bauxite mining concession

A digital surface model (DSM) is used to characterize the landscape and topical karst landforms within a bauxite mining lease in north central Jamaica. Five case study sites are selected for detailed geomorphic analysis and cartographic visualization using a GIS. In Jamaica, tropical cockpit karst landscapes are composed of several landforms: cockpits, glades, corridors, saddles, and talus slopes. Evidence for the existence and quantification of these landforms is provided in this paper. Study sites have a mean basin area of 96,514 m2 , an average highest elevation of 541 m, mean lowest point of 444 m, with an average enclosed depression depth of 97 m. Depth and slope values within the study sites are consistent with previously published literature for cockpit karst landscapes. The literature also supports the findings in this study which are steep and convex slopes surrounding cockpit floors

“What’ll Thou Have”: Quakers and the Characterization of Tavern Sites in Colonial Philadelphia

In 1766, Ebenezer Robinson, an active Quaker and middle-class tradesman, was one of the first to develop the land just north of Independence Hall, then at the edge of urban Philadelphia. Recent work on Independence Mall sponsored jointly by the National Park Service and the National Constitution Center has uncovered several features on this property, but analysis and historical documentation has suggested that a low-class tavern occupied the spot while Robinson owned it. This paper examines artifacts from a privy associated with this period of the site and compares the finds with several other sites to characterize this tavern, explore the different roles taverns played in colonial communities, and clarify the relationship of the tavern with its Quaker landlord. The study is further contextualized with a discussion of Quakerism and attitudes towards alcohol in the colonial period

Practicing and Preaching Quakerism: Creating a Religion of Peace on a Slavery‐Era Plantation

A meeting of the Religious Society of Friends (“Quakers”) formed in the British Virgin Islands in the 1740s offers a window onto broader practices of religion making. Equality, simplicity, and peace form a basis for Quaker thought, but in the BVI these ideals intersected with the realities of Caribbean life and the central fact that members also held enslaved Africans. What members did to create Quakerism varied for this group, yet it was nonetheless understood to be a part of the broader community of “Friends.” Practice perspectives are employed here to gain access to seemingly ephemeral religion through the concrete objects of archaeology but also as a means of reconciling variation in practice with the idea of a coherent religion. Here religious identity was negotiated through practices on multiple scales, creating unity via larger‐scope practices of writing and reading while the most frequent identifications were local and variable. Written works are often seen to encode a static, “real” version of religion against which actions can be measured, but I will argue that religion is better seen in practice, and here Quakerism was created at least as much in the variable minutia of individual performance as in widely shared documents. RESUMEN Una reunión de la Sociedad Religiosa de Amigos (Cuáqueros) formada en las Islas Vírgenes Británicas (IVB) en los años 1740s ofrece una ventana hacia prácticas más amplias de formación de religión. Igualdad, simplicidad, y paz forman una base para el pensamiento cuáquero, pero en las IVB estos ideales intersectaron con las realidades de la vida caribeña y el hecho central que también miembros retuvieron africanos esclavizados. Lo que los miembros hicieron para crear cuaquerismo fue diferente para este grupo, sin embargo, aún así, fue entendido como parte de una comunidad de “Amigos” más amplia. Perspectivas de la práctica son empleadas aquí para ganar acceso a una religión aparentemente efímera a través de objetos concretos de arqueología, pero también como un medio de reconciliar la variación en práctica con la ideas de una religión coherente. Aquí la identidad religiosa fue negociada a través de prácticas en escalas múltiples, creando unidad a través de prácticas de escritura y lectura de mayor alcance mientras las identificaciones más frecuentes fueron locales y variables. Trabajos escritos a menudo se ven como codificando una versión estática, “real” de la religión en contra de la cual acciones pueden ser medidas, pero argumentaré que la religión es mejor vista en práctica, y aquí Cuaquerismo fue creado al menos tanto en minucias variables de desempeños individuales como en documentos ampliamente compartidos.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106773/1/aman12074.pd

Bioenergetic and economic impacts of humpback whale depredation at salmon hatchery release sites

Thesis (Ph.D.) University of Alaska Fairbanks, 2018Since 2008, humpback whales have been documented depredating hatchery-produced juvenile salmon, a novel prey, at points of their release in Southeast Alaska. The objectives of this dissertation are to determine the spatial distribution, seasonal distribution, and frequency of humpback whale foraging at release sites, determine whether whale presence is affecting the economic productivity of hatchery operations, and compare the bioenergetic benefits for whales feeding on juvenile salmon at hatchery release sites relative to typical prey. Five hatchery release sites were monitored over six years during the spring release season for whale presence/absence, numbers, and behaviors. Linear models were used to determine that for coho salmon, cohorts with frequent humpback whale presence had lower marine survival than cohorts with less or no humpback whale presence, but this was not seen for chum or Chinook salmon. Over six years, these sites lost an estimated 23% of revenue from coho salmon totaling almost a million dollars per year in addition to increased rearing costs to mitigate whale predation. A process model was developed to compare the net energy gain for humpback whales foraging on krill, herring and juvenile salmon. Whales were found to feed profitably on krill and chum salmon where they occurred in dense enough distributions and on herring when large coordinated groups impeded the escape of prey. Coho salmon typically distributed too diffusely for humpback whales to recuperate the full energetic costs of engulfment, indicating that behaviors such as bubble net feeding may be essential for increasing prey aggregation to an energetically profitable level, or humpback whales may be feeding to mitigate energetic losses. As intraspecific competition increases due to recovery and or changes to prey resources, generalist humpback whales may expand feeding to exploit new and less profitable prey resources