A focus on critical aspects of uptake and transport of milk-derived extracellular vesicles across the Caco-2 intestinal barrier model

Bovine milk-derived extracellular vesicles (EVs) hold promises as oral drug delivery systems. Since EV bioavailability studies are difficult to compare, key factors regarding EV uptake and intestinal permeability remain little understood. This work aims to critically study uptake and transport properties of milk-derived EVs across the intestinal barrier in vitro by standardization approaches. Therefore, uptake properties were directly compared to liposomes in intestinal Caco-2 cells. Reliable staining results were obtained by the choice of three distinct EV labeling sites, while non-specific dye transfer and excess dye removal were carefully controlled. A novel fluorescence correction factor was implemented to account for different labelling efficiencies. Both EV and liposome uptake occurred mainly energy dependent with the neonatal Fc receptor (FcRn) providing an exclusive active pathway for EVs. Confocal microscopy revealed higher internalization of EVs whereas liposomes rather remained attached to the cell surface. Internalization could be improved when changing the liposomal formulation to resemble the EV lipid composition. In a Caco-2/HT29-MTX co-culture liposomes and EVs showed partial mucus penetration. For transport studies across Caco-2 monolayers we further established a standardized protocol considering the distinct requirements for EVs. Especially insert pore sizes were systematically compared with 3 µm inserts found obligatory. Obtained apparent permeability coefficients (Papp) reflecting the transport rate will allow for better comparison of future bioavailability testing

Audit report on Jackson County, Iowa for the year ended June 30, 2016

Audit report on Jackson County, Iowa for the year ended June 30, 201

Detection of cannabinoid receptor type 2 in native cells and zebrafish with a highly potent, cell-permeable fluorescent probe.

Despite its essential role in the (patho)physiology of several diseases, CB2R tissue expression profiles and signaling mechanisms are not yet fully understood. We report the development of a highly potent, fluorescent CB2R agonist probe employing structure-based reverse design. It commences with a highly potent, preclinically validated ligand, which is conjugated to a silicon-rhodamine fluorophore, enabling cell permeability. The probe is the first to preserve interspecies affinity and selectivity for both mouse and human CB2R. Extensive cross-validation (FACS, TR-FRET and confocal microscopy) set the stage for CB2R detection in endogenously expressing living cells along with zebrafish larvae. Together, these findings will benefit clinical translatability of CB2R based drugs

1.02.078: University officials leave Memorial University of Newfoundland to attend convocation at St. Patrick's Hall

University officials leave Memorial University of Newfoundland to attend convocation at St. Patrick's Hall

Experiments and fracture modeling of high-strength pipelines for high and low stress triaxialities

This paper provides results from a comprehensive study on mechanical characterization of high-strength pipeline steel, grade X100 using experimental and numerical methods. The material was characterized for anisotropic plasticity, fracture initiation for various states of stress, (pre-cracked) fracture toughness and uncracked ductility. The experimental program included tests on flat butterfly-shaped, central hole, notched and circular disk specimens for low stress triaxiality levels; as well as tests on round notched bar specimens and SENT fracture mechanics tests, for high values of stress triaxiality. This program covered a wide range of stress conditions and demonstrated its effect on the material resistance. Parallel to the experimental study, detailed numerical investigations were carried out to simulate all different experimental tests. Using an inverse method, a 3-parameter calibration was performed on the Modified Mohr-Coulomb (MMC) fracture model. Subsequently, the predictive capabilities of the MMC were evaluated by the comparison to the fracture toughness tests results, used extensively in the pipeline industry. The capabilities of the MIT fracture model have been demonstrated on an example of high strength offshore steel, X100. The outcome of this study was not only to provide, the overall characterization of the fracture behavior of this material as an example, but also to present the methodology on how to use the MMC model as a practical tool in pipeline design

Behavioral Monitoring Tool for Pig Farmers: Ear Tag Sensors, Machine Intelligence, and Technology Adoption Roadmap

Precision swine production can benefit from autonomous, noninvasive, and affordable devices that conduct frequent checks on the well-being status of pigs. Here, we present a remote monitoring tool for the objective measurement of some behavioral indicators that may help in assessing the health and welfare status—namely, posture, gait, vocalization, and external temperature. The multiparameter electronic sensor board is characterized by laboratory measurements and by animal tests. Relevant behavioral health indicators are discussed for implementing machine learning algorithms and decision support tools to detect animal lameness, lethargy, pain, injury, and distress. The roadmap for technology adoption is also discussed, along with challenges and the path forward. The presented technology can potentially lead to efficient management of farm animals, targeted focus on sick animals, medical cost savings, and less use of antibiotics.This article is published as Pandey, Santosh, Upender Kalwa, Taejoon Kong, Baoqing Guo, Phillip C. Gauger, David J. Peters, and Kyoung-Jin Yoon. "Behavioral Monitoring Tool for Pig Farmers: Ear Tag Sensors, Machine Intelligence, and Technology Adoption Roadmap." Animals 11, no. 9 (2021): 2665. DOI: 10.3390/ani11092665. Copyright 2021 by the authors. Attribution 4.0 International (CC BY 4.0). Posted with permission