Alien Registration- Crowell, Charles M. (Portland, Cumberland County)

https://digitalmaine.com/alien_docs/24296/thumbnail.jp

Alien Registration- Crowell, Charles M. (Portland, Cumberland County)

https://digitalmaine.com/alien_docs/24296/thumbnail.jp

Molecular engineering improves antigen quality and enables integrated manufacturing of a trivalent subunit vaccine candidate for rotavirus

Background Vaccines comprising recombinant subunit proteins are well-suited to low-cost and high-volume production for global use. The design of manufacturing processes to produce subunit vaccines depends, however, on the inherent biophysical traits presented by an individual antigen of interest. New candidate antigens typically require developing custom processes for each one and may require unique steps to ensure sufficient yields without product-related variants. Results We describe a holistic approach for the molecular design of recombinant protein antigens—considering both their manufacturability and antigenicity—informed by bioinformatic analyses such as RNA-seq, ribosome profiling, and sequence-based prediction tools. We demonstrate this approach by engineering the product sequences of a trivalent non-replicating rotavirus vaccine (NRRV) candidate to improve titers and mitigate product variants caused by N-terminal truncation, hypermannosylation, and aggregation. The three engineered NRRV antigens retained their original antigenicity and immunogenicity, while their improved manufacturability enabled concomitant production and purification of all three serotypes in a single, end-to-end perfusion-based process using the biotechnical yeast Komagataella phaffii. Conclusions This study demonstrates that molecular engineering of subunit antigens using advanced genomic methods can facilitate their manufacturing in continuous production. Such capabilities have potential to lower the cost and volumetric requirements in manufacturing vaccines based on recombinant protein subunits

Emotion regulation

Synonyms: emotional control; emotion-related self-regulation; stress-regulation; mood-regulation; affect-regulation; emotional intelligence Definition: Emotion regulation refers to the conscious or unconscious processes of monitoring, evaluating, modulating, and managing emotional experiences and expression of emotion in terms of intensity, form, and duration of feelings, emotion-related physiological states and behaviors

Guidelines for Genome-Scale Analysis of Biological Rhythms

Genome biology approaches have made enormous contributions to our understanding of biological rhythms, particularly in identifying outputs of the clock, including RNAs, proteins, and metabolites, whose abundance oscillates throughout the day. These methods hold significant promise for future discovery, particularly when combined with computational modeling. However, genome-scale experiments are costly and laborious, yielding “big data” that are conceptually and statistically difficult to analyze. There is no obvious consensus regarding design or analysis. Here we discuss the relevant technical considerations to generate reproducible, statistically sound, and broadly useful genome-scale data. Rather than suggest a set of rigid rules, we aim to codify principles by which investigators, reviewers, and readers of the primary literature can evaluate the suitability of different experimental designs for measuring different aspects of biological rhythms. We introduce CircaInSilico, a web-based application for generating synthetic genome biology data to benchmark statistical methods for studying biological rhythms. Finally, we discuss several unmet analytical needs, including applications to clinical medicine, and suggest productive avenues to address them

Guidelines for Genome-Scale Analysis of Biological Rhythms

Genome biology approaches have made enormous contributions to our understanding of biological rhythms, particularly in identifying outputs of the clock, including RNAs, proteins, and metabolites, whose abundance oscillates throughout the day. These methods hold significant promise for future discovery, particularly when combined with computational modeling. However, genome-scale experiments are costly and laborious, yielding ‘big data’ that is conceptually and statistically difficult to analyze. There is no obvious consensus regarding design or analysis. Here we discuss the relevant technical considerations to generate reproducible, statistically sound, and broadly useful genome scale data. Rather than suggest a set of rigid rules, we aim to codify principles by which investigators, reviewers, and readers of the primary literature can evaluate the suitability of different experimental designs for measuring different aspects of biological rhythms. We introduce CircaInSilico, a web-based application for generating synthetic genome biology data to benchmark statistical methods for studying biological rhythms. Finally, we discuss several unmet analytical needs, including applications to clinical medicine, and suggest productive avenues to address them

Alien Registration- Crowell, Charles M. (Portland, Cumberland County)

https://digitalmaine.com/alien_docs/24296/thumbnail.jp

Measurement and Quantification of Gross Human Shoulder Motion

The shoulder girdle plays an important role in the large pointing workspace that humans enjoy. The goal of this work was to characterize the human shoulder girdle motion in relation to the arm. The overall motion of the human shoulder girdle was characterized based on motion studies completed on test subjects during voluntary (natural/unforced) motion. The collected data from the experiments were used to develop surface fit equations that represent the position and orientation of the glenohumeral joint for a given humeral pointing direction. These equations completely quantify gross human shoulder girdle motion relative to the humerus. The equations are presented along with goodness-of-fit results that indicate the equations well approximate the motion of the human glenohumeral joint. This is the first time the motion has been quantified for the entire workspace, and the equations provide a reference against which to compare future work

First generation anticoagulant rodenticide persistence in large mammals and implications for wildlife management

The use of first generation anticoagulants by the Department of Conservation (DOC) for rodent control has increased in recent years. This study estimates the likely hepatic persistence time of diphacinone in red deer, pigs and cattle exposed to a single sublethal dose, as well as coumatetralyl in red deer. Red deer were given an initial dose of either 1.5 mg/kg diphacinone or 8.25 mg/kg coumatetralyl, which equated to a similar quantity of commercially available bait for these anticoagulants. At these initial doses, the mean hepatic elimination half-life of diphacinone in red deer is estimated as 6.0 days whereas the mean estimated hepatic elimination half-life of coumatetralyl is estimated as 18.9 days. In pigs given an initial dose of 1.5 mg/kg, the mean hepatic elimination half-life is estimated as 12.4 days. Cattle were dosed with 1.5 mg/kg diphacinone in two similar trials. The results suggest that diphacinone is metabolised and distributed quite differently in cattle from the other species studied, including longer hepatic persistence. It would be valuable to investigate hepatic persistence of other anticoagulants in cattle to inform withholding periods for livestock in the case of accidental exposure. © 2013 Copyright The Royal Society of New Zealand