Ham, Eggs, and Corn Cake: A Nebraska Territory Diary

The diary of Erastus Flavel Beadle is the diary of a man lured by the myth of the West as a place of adventure, a new start, a chance to get rich. It is also the diary of a man who faced realities that drew him back to the East, from which he had come. The diary is one man’s brief account of life in Nebraska Territory in 1857, and it provides snapshots of a human drama as it plays out in business, culture, and politics. Beadle’s diary furnishes a picture of the reality of one small piece of the nineteenth-century American West and a glimpse into the dreams and hopes of a group of men for the creation and future of Saratoga, a western city to rival all others (see map 1). Three years after the Kansas-Nebraska Act embroiled the plains states in a struggle that presaged the war to come, the irrepressible Erastus F. Beadle left his home in Buffalo, New York, and set out for the territories to see about some land. Specifically, Beadle had a stake in the Sulphur Springs Land Company, an enterprise that proposed to build the community of Saratoga just north of Omaha for prospective settlers, who were arriving by the boatload. In diary pages and letters home, Beadle noted his impressions—the details, anecdotes, and characters that filled his days—and in doing so, left a remarkable record of a bygone way of life in the American West. Beginning with his three-month journey westward, Beadle takes us from the hardships and amusements of travel on the Big Muddy to the magnificent sight of a prairie fire at night, from the political propaganda abroad in the slavery stronghold of Kansas to the realities of doing business on the Nebraska frontier. Whether describing roads or water routes, mishaps or accommodations, finances, politics, or daily life, Beadle writes with an immediacy and character that make his diary as entertaining as it is informative—a living, intimate chapter of American history. This excerpt includes the Introduction and the Diary through March 25, 1857 (17 pages)

Considerations for Observational Research Using Large Data Sets in Radiation Oncology

The radiation oncology community has witnessed growing interest in observational research conducted using large-scale data sources such as registries and claims-based datasets. With the growing emphasis on observational analyses in health care, the radiation oncology community must possess a sophisticated understanding of the methodological considerations of such studies in order to evaluate evidence appropriately to guide practice and policy. Because observational research has unique features that distinguish it from clinical trials and other forms of traditional radiation oncology research, the Red Journal assembled a panel of experts in health services research to provide a concise and well-referenced review, intended to be informative for the lay reader, as well as for scholars who wish to embark on such research without prior experience. This review begins by discussing the types of research questions relevant to radiation oncology that large-scale databases may help illuminate. It then describes major potential data sources for such endeavors, including information regarding access and insights regarding the strengths and limitations of each. Finally, it provides guidance regarding the analytic challenges that observational studies must confront, along with discussion of the techniques that have been developed to help minimize the impact of certain common analytical issues in observational analysis. Features characterizing a well-designed observational study include clearly defined research questions, careful selection of an appropriate data source, consultation with investigators with relevant methodological expertise, inclusion of sensitivity analyses, caution not to overinterpret small but significant differences, and recognition of limitations when trying to evaluate causality. This review concludes that carefully designed and executed studies using observational data that possess these qualities hold substantial promise for advancing our understanding of many unanswered questions of importance to the field of radiation oncology

Genetic selection reveals the role of a buried, conserved polar residue

The burial of nonpolar surface area is known to enhance markedly the conformational stability of proteins. The contribution from the burial of polar surface area is less clear. Here, we report on the tolerance to substitution of Ser75 of bovine pancreatic ribonuclease (RNase A), a residue that has the unusual attributes of being buried, conserved, and polar. To identify variants that retain biological function, we used a genetic selection based on the intrinsic cytotoxicity of ribonucleolytic activity. Cell growth at 30°C, 37°C, and 44°C correlated with residue size, indicating that the primary attribute of Ser75 is its small size. The side-chain hydroxyl group of Ser75 forms a hydrogen bond with a main-chain nitrogen. The conformational stability of the S75A variant, which lacks this hydrogen bond, was diminished by ΔΔG = 2.5 kcal/mol. Threonine, which can reinstate this hydrogen bond, provided a catalytically active RNase A variant at higher temperatures than did some smaller residues (including aspartate), indicating that a secondary attribute of Ser75 is the ability of its uncharged side chain to accept a hydrogen bond. These results provide insight on the imperatives for the conservation of a buried polar residue