Prediction of Antibody Viscosity from Dilute Solution Measurements.

The high antibody doses required to achieve a therapeutic effect often necessitate high-concentration products that can lead to challenging viscosity issues in production and delivery. Predicting antibody viscosity in early development can play a pivotal role in reducing late-stage development costs. In recent years, numerous efforts have been made to predict antibody viscosity through dilute solution measurements. A key finding is that the entanglement of long, flexible complexes contributes to the sharp rise in antibody viscosity at the required dosing. This entanglement model establishes a connection between the two-body binding affinity and the many-body viscosity. Exploiting this insight, this study connects dilute solution measurements of self-association to high-concentration viscosity profiles to quantify the relationship between these regimes. The resulting model has exhibited success in predicting viscosity at high concentrations (around 150 mg/mL) from dilute solution measurements, with only a few outliers remaining. Our physics-based approach provides an understanding of fundamental physics, interpretable connections to experimental data, the potential to extrapolate beyond training conditions, and the capacity to effectively explain the physical mechanics behind these outliers. Conducting hypothesis-driven experiments that specifically target the viscosity and relaxation mechanisms of outlier molecules may allow us to unravel the intricacies of their behavior and, in turn, enhance the performance of our model.

Yield gap analysis of rainfed alfalfa in the United States.

The United States (US) is the largest alfalfa (Medicago sativa L.) producer in the world. More than 44% of the US alfalfa is produced under rainfed conditions, although it requires a relatively high amount of water compared to major field crops. Considering that yield and production of rainfed alfalfa have been relatively stagnant in the country for decades, there is a need to better understand the magnitude of yield loss due to water limitation and how far from yield potential current yields are. In this context, the main objective of this study was to estimate the current yield gap of rainfed alfalfa in the US. We collected 10 year (2009-2018) county-level government-reported yield and weather data from 393 counties within 12 major US rainfed alfalfa producing states and delineated alfalfa growing season using probabilistic approaches based on temperature thresholds for crop development. We then calculated county-level growing season rainfall (GSR), which was plotted against county-level yield to determine attainable yield (Ya) using frontier function analysis, and water-limited potential yield (Yw) using boundary function analysis. Average and potential water use efficiencies (WUE) were estimated, and associated yield gap referring to attainable (YGa) or water-limited yields (YGw) were calculated. Finally, we used conditional inference trees (CIT) to identify major weather-related yield-limiting factors to alfalfa forage yield. The frontier model predicted a mean Ya of 9.6 ± 1.5 Mg ha-1 and an associated optimum GSR of 670 mm, resulting in a mean YGa of 34%. The boundary function suggested a mean Yw of 15.3 ± 3 Mg ha-1 at the mean GSR of 672 ± 153 mm, resulting in a mean yield gap of 58%. The potential alfalfa WUE was 30 kg ha-1 mm-1 with associated minimum water losses of 24% of mean GSR, which was three times greater than the mean WUE of 10 kg ha-1 mm-1. The CIT suggested that GSR and minimum temperature in the season were the main yield-limiting weather variables in rainfed alfalfa production in the US. Our study also revealed that alfalfa was only limited by water availability in 21% of the environments. Thus, future research on management practices to narrow yield gaps at current levels of water supply is necessary.

Structure-Function Properties in Disordered Condensates.

Biomolecular condensates appear throughout the cell serving a wide variety of functions. Many condensates appear to form by the assembly of multivalent molecules, which produce phase-separated networks with liquidlike properties. These networks then recruit client molecules, with the total composition providing functionality. Here we use a model system of poly-SUMO and poly-SIM proteins to understand client-network interactions and find that the structure of the network plays a strong role in defining client recruitment and thus functionality. The basic unit of assembly in this system is a zipperlike filament composed of alternating poly-SUMO and poly-SIM molecules. These filaments have defects of unsatisfied bonds that allow for both the formation of a 3D network and the recruitment of clients. The filamentous structure constrains the scaffold stoichiometries and the distribution of client recruitment sites that the network can accommodate. This results in a nonmonotonic client binding response that can be tuned independently by the client valence and binding energy. These results show how the interactions within liquid states can be disordered yet still contain structural features that provide functionality to the condensate.

Accuracy of clinical diagnosis of benign eyelid lesions: Is a dedicated nurse-led service safe and effective?

This article compares an independent nurse-led benign lesion service with a doctor-led one, and assesses the impact of clinician seniority on diagnostic accuracy rates. Retrospective review of benign lesions referred to a teaching hospital and managed in either a doctor- or nurse-led lid service. All lesions were diagnosed clinically, excised and then sent for histological diagnosis. Lesions were categorized into subtypes. Pre-excision clinical diagnoses were compared with histological diagnoses. Sensitivity, specificity and missed malignancy rates were calculated for each subtype. Accuracy was compared between different grades of doctors and a specialist nurse. 264 and 332 lesions were managed in a doctor-led and nurse-led service, respectively. Rates of accurate sub-typing were 79.6% and 80.4% in the doctor- and nurse-led services, respectively (p > 0.05). Clinician seniority had no bearing. Missed malignancies or pre-malignancies accounted for 1.1% and 1.5% of lesions in the doctor and nurse-led services, respectively (p > 0.05). Overall, the remaining misdiagnoses were benign lesions of another subtype (13.6%) or non-specific histological findings (5.0%) and 98.6% of lesions were confirmed as benign on histology. Overall sensitivity and specificity values were: benign epithelial proliferations 95.6% and 92.2%, epidermal inclusion cysts 92.2% and 88.0%, xanthelasma 97.5% and 100.0%, cysts of Moll 66.7% and 96.6%, naevi 39.4% and 99.8% and molluscum 20.0% and 99.8%, respectively. A dedicated nurse-led service is as effective in managing a range of clinically benign lid lesions as a doctor-led one, and clinician seniority has little impact on the diagnostic accuracy of these lesions.