Introduction to The Bremer-Kovacs Collection: Historic Documents Related to the Administrative Procedure Act of 1946 (HeinOnline 2021)

Few statutes have a legislative history as rich, varied, and sprawling as the Administrative Procedure Act of 1946 (APA). In recent years, courts and scholars have shown increased interest in understanding this history. This is no mean feat. The APA’s history spans nearly two decades, and it includes numerous failed bills, a presidential veto, and a full panoply of congressional documents. In addition, much of the most crucial documentation underlying the APA was produced outside of Congress—by the executive branch—and even outside of government—by the American Bar Association. Identifying and locating all the relevant documents is difficult. Understanding each piece in its proper historical context is downright daunting.The Bremer-Kovacs Collection: Historic Documents Related to the Administrative Procedure Act of 1946, now available on HeinOnline, is a comprehensive collection designed to make the APA’s history more accessible and understandable. It brings together in the same place—for the first time and in an easily navigable electronic format—all the documents that chart the path to the APA’s enactment. It also includes a suite of tools designed to assist both new and seasoned researchers in understanding the statute and its history. This essay is part of the suite, offering a concise, narrative introduction to the Collection that will help users get started and understand the historical context and importance of the included documents

Quantitative changes in intracellular calcium and extracellular-regulated kinase activation measured in parallel in CHO cells stably expressing serotonin (5-HT) 5-HT2A or 5-HT2C receptors

<p>Abstract</p> <p>Background</p> <p>The serotonin (5-HT) 2A and 2C receptors (5-HT_2AR and 5-HT_2CR) are involved in a wide range of physiological and behavioral processes in the mammalian central and peripheral nervous systems. These receptors share a high degree of homology, have overlapping pharmacological profiles, and utilize many of the same and richly diverse second messenger signaling systems. We have developed quantitative assays for cells stably expressing these two receptors involving minimal cell sample manipulations that dramatically improve parallel assessments of two signaling responses: intracellular calcium (<it>Ca_i</it>⁺⁺) changes and activation (phosphorylation) of downstream kinases. Such profiles are needed to begin to understand the simultaneous contributions from the multiplicity of signaling cascades likely to be initiated by serotonergic ligands.</p> <p>Results</p> <p>We optimized the <it>Ca_i</it>⁺⁺assay for stable cell lines expressing either 5-HT_2AR or 5-HT_2CR (including dye use and measurement parameters; cell density and serum requirements). We adapted a quantitative 96-well plate immunoassay for pERK in the same cell lines. Similar cell density optima and time courses were observed for 5-HT_2AR- and 5-HT_2CR-expressing cells in generating both types of signaling. Both cell lines also require serum-free preincubation for maximal agonist responses in the pERK assay. However, 5-HT_2AR-expressing cells showed significant release of <it>Ca_i</it>⁺⁺in response to 5-HT stimulation even when preincubated in serum-replete medium, while the response was completely eliminated by serum in 5-HT_2CR-expressing cells. Response to another serotonergic ligand (DOI) was eliminated by serum-replete preincubation in both cells lines.</p> <p>Conclusions</p> <p>These data expand our knowledge of differences in ligand-stimulated signaling cascades between 5-HT_2AR and 5-HT_2CR. Our parallel assays can be applied to other cell and receptor systems for monitoring and dissecting concurrent signaling responses.</p

Effect of distillers grains moisture and inclusion level in livestock diets on greenhouse gas emissions in the corn-ethanol-livestock life cycle

A model was previously developed (Biofuel Energy Systems Simulator; www. bess.unl.edu) to predict greenhouse gas (GHG) emissions and net energy yield when ethanol is produced from corn. The model also predicts feedlot cattle, dairy cattle, and swine performance and feed replacement value of ethanol coproducts. Updated equations that predict performance of feedlot cattle fed 0 to 40% of dietary DM as corn wet (WDGS), modified (MDGS), or dry (DDGS) distillers grains plus solubles replacing dry-rolled and high-moisture corn were developed and incorporated into the model. Equations were derived from pen-level performance for 20 finishing studies evaluating WDGS, 4 evaluating MDGS, and 4 evaluating DDGS conducted at the University of Nebraska. Feeding value of WDGS was 145 to 131% of corn replaced when included at 20 to 40% of diet DM due to a quadratic (P \u3c 0.01) increase in G:F. The feeding value of MDGS was 124 to 117% with a quadratic (P \u3c 0.01) increase in G:F and 112 to 110% for DDGS with a linear (P \u3c 0.01) increase in G:F. Midwest corn-ethanol-livestock life cycle GHG reduction relative to gasoline (97.7 g CO2 equivalent/MJ of ethanol) was 61 to 57% when WDGS was fed to feedlot cattle for 20 to 40% diet inclusion. Feeding MDGS and DDGS to feedlot cattle reduced GHG emissions from the corn-ethanol-cattle system by 53 to 50% and 46 to 41%, respectively. Feeding WDGS to feedlot cattle was the optimum feed use of distillers grains plus solubles based on feeding performance and GHG reduction

Briefing: Young Coastal Scientists and Engineers Conference 2013

On 25–26 March 2013, 52 early career scientists and engineers, studying various aspects of coastal science, met at the University of Aberdeen for the ninth Young Coastal Scientists and Engineers Conference. The conference was jointly organised by the School of Engineering, University of Aberdeen, and Marine Scotland Science. Early-career scientists, researchers and practitioners presented 23 oral and 17 poster presentations over the 2-day meeting. The papers all had a coastal theme with a large diversity in the subjects covered, including waves, currents, tidal energy, coastal erosion, sediment transport, fluid mechanics and particle tracking. This briefing paper reports on the conference, and presents the keynote lecture and four papers voted to be of especially high quality by the panel of judges

Wet Distillers Grains Plus Solubles or Solubles in Feedlot Diets Containing Wet Corn Gluten Feed

Effects of the addition of 0% to 40% wet distillers grains plus solubles (WDGS) or 0% to 20% condensed corn distillers solubles (CCDS) to feedlot diets containing high moisture corn (HMC) and 35% wet corn gluten feed (WCGF) were evaluated. As WDGS replaced HMC, average daily gain (ADG) decreased linearly and dry matter intake (DMI) tended to decrease. Replacement of HMC with WDGS in the 35% WCGF diet caused a linear decrease in ADG and a trend for a linear decrease in DMI. When CCDS replaced HMC, no difference in steer performance was observed. The sulfur content, rather than fat content, of WDGS may be the limiting factor with feeding WDGS in combination with WCGF, and solubles may effectively reduce the dietary inclusion of corn by up to 20% of diet DM in finishing diets containing 35% WCGF

Relationship Between Morbidity and Performance in Feedlot Cattle

Five datasets from Canada, Oklahoma, Illinois, and Nebraska were used to determine the impact of bovine respiratory disease (BRD) on performance, with emphasis on dry matter intake (DMI) and feed to gain ratio (F:G). Data included pens and individually fed cattle. In general, cattle treated for BRD had lower DMI and average daily gain (ADG) with little to no effect on F:G. When BRD occured early in the feeding period (days), little change in performance was observed

A time-resolved proteomic and prognostic map of COVID-19

COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease

Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.NovartisEli Lilly and CompanyAstraZenecaAbbViePfizer UKCelgeneEisaiGenentechMerck Sharp and DohmeRocheCancer Research UKGovernment of CanadaArray BioPharmaGenome CanadaNational Institutes of HealthEuropean CommissionMinistère de l'Économie, de l’Innovation et des Exportations du QuébecSeventh Framework ProgrammeCanadian Institutes of Health Researc