Second Story

Winner of the 2022 Barry Hannah Prize in Fiction, judged by Deesha Philya

Meet and Greet

A collection of original short stories

Definition of a platform continuous capture scale down model and link to scale-up for monoclonal antibody clinical manufacturing

Definition and scale-up of a batch chromatography process is based on a few main variables such as linear velocity, column loading, and bed height, which are scaled proportionally to column volume. Continuous chromatography consists of multiple columns with column loading and washes/elution/regeneration occurring simultaneously. The definition of a small scale method for continuous chromatography can be extremely complex due to the extensive number of method variables. Limited knowledge exists for development of a scale down and up strategy for continuous chromatography. This abstract should provide some insight into case studies on integration of continuous operations and scale-up, which is one of the themes of the integrated continuous biomanufacturing (ICB) conference. This presentation will describe a strategy for definition of a platform continuous capture scale down model and scale-up pathway. The platform continuous capture step utilizes periodic counter-current chromatography (PCC) for operation of affinity chromatography in a semi-continuous manner. A scale down model for the PCC step was defined and simplified to the following three ranges of harvested cell culture fluid (HCCF) titers: ≤ 2 g/L, 2.5-8 g/L, and 8.5-13 g/L. For each of the three titer ranges, the following variable setpoints are changed based on the specific HCCF titer range: step linear velocity, number of columns, column size, and ΔUV. After these setpoints are inputted into the algorithm, PCC method variables, such as sample loading flowrate, loop time, number of loops and cycles, throughput (g/L/hr), and time cycle, will populate to finish the method design. This PCC scale down model was utilized to scale-up to a bioreactor range of 500-2000L. Quality results showed a good correlation between scale down model and scale-up data. Additional parameters for the 2000L scale-up run included assessment of cleaning and drug substance stability. The cleaning results of the continuous chromatography skid showed passing bioburden, endotoxin, and conductivity. Drug substance stability was also maintained for a year, which was the study duration. This data set proves the PCC small scale model data is representative of the scale-up quality results. In addition, targets such as skid cleanability and DS stability met specifications, which supports the scale-up package for implementation of a platform continuous capture step into a purification process for clinical mAb manufacturing

SNANA: A Public Software Package for Supernova Analysis

We describe a general analysis package for supernova (SN) light curves, called SNANA, that contains a simulation, light curve fitter, and cosmology fitter. The software is designed with the primary goal of using SNe Ia as distance indicators for the determination of cosmological parameters, but it can also be used to study efficiencies for analyses of SN rates, estimate contamination from non-Ia SNe, and optimize future surveys. Several SN models are available within the same software architecture, allowing technical features such as K-corrections to be consistently used among multiple models, and thus making it easier to make detailed comparisons between models. New and improved light-curve models can be easily added. The software works with arbitrary surveys and telescopes and has already been used by several collaborations, leading to more robust and easy-to-use code. This software is not intended as a final product release, but rather it is designed to undergo continual improvements from the community as more is learned about SNe. Below we give an overview of the SNANA capabilities, as well as some of its limitations. Interested users can find software downloads and more detailed information from the manuals at http://www.sdss.org/supernova/SNANA.html .Comment: Accepted for publication in PAS

The Core Collapse Supernova Rate from the SDSS-II Supernova Survey

We use the Sloan Digital Sky Survey II Supernova Survey (SDSS-II SNS) data to measure the volumetric core collapse supernova (CCSN) rate in the redshift range (0.03<z<0.09). Using a sample of 89 CCSN we find a volume-averaged rate of (1.06 +/- 0.19) x 10**(-4)/(yr Mpc**3) at a mean redshift of 0.072 +/- 0.009. We measure the CCSN luminosity function from the data and consider the implications on the star formation history.Comment: Minor corrections to references and affiliations to conform with published versio

Design of a GMP-ready single-pass tangential flow filtration (SPTFF) and inline diafiltration (LILDF) system for continuous manufacturing operations

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Water availability, root depths and 2017 crop yields

During 2016 and 2017, June-July precipitation was below normal in many parts of Iowa creating midseason concerns about potential yield loss due to water stress. However, these concerns were not realized. In contrast, 2016 and 2017 crop yields over-performed yields obtained in many years with average of above average June-July precipitation. In Iowa, deep root systems, high soil water storage capacity, and shallow water tables are common explanations for high yields in years with below normal precipitation. How deep can roots grow? How much does groundwater contribute to the yields? To answer these questions and more, the Forecast and Assessment of Cropping sysTemS (FACTS) project was established in 201

Establishment of environmentally sensitive DNA methylation states in the very early human embryo.

The molecular mechanisms responsible for the developmental origins of later disease are currently unknown. We previously demonstrated that women's periconceptional nutrition predicts their offspring's DNA methylation at metastable epialleles (MEs). We present a genome-wide screen yielding 687 MEs and track their trajectories across nine developmental stages in human in vitro fertilization embryos. MEs exhibit highly unusual methylation dynamics across the implantation-gastrulation transition, producing a large excess of intermediate methylation states, suggesting the potential for differential programming in response to external signals. Using a natural experiment in rural Gambia, we show that genomic regions sensitive to season of conception are highly enriched for MEs and show similar atypical methylation patterns. MEs are enriched for proximal enhancers and transcription start sites and are influenced by genotype. Together, these observations position MEs as distinctive epigenomic features programmed in the early embryo, sensitive to genetic and periconceptional environment, and with the potential to influence phenotype

A search for broad infrared recombination lines in NGC 1068

We report infrared spectroscopy of the prototypical Seyfert 2 galaxy NGC 1068, aiming at detection of broad components of hydrogen recombination lines that originate in the obscured broad-line region. Using the Short Wavelength Spectrometer on board the Infrared Space Observatory, we have observed for the first time the regions of Brackett beta 2.626um and Pfund alpha 7.460um, and present improved data for Brackett alpha 4.052um. No significant broad components are detected, implying an equivalent visual extinction to the broad-line region of at least 50 magnitudes and an obscuring column density of at least 10^23 cm^-2. While consistent with a highly obscured broad-line region, as required by the classical unified scenario, these limits are not yet significant enough to discriminate strongly between different torus models or to constrain properties of the gas causing the very large X-ray obscuration. We discuss the systematic limitations of infrared broad-line region searches and suggest that Brackett alpha may often be the most favorable transition for future searches.Comment: aastex (V4), 4 eps figures. Accepted by Ap