Automated multifactorial design of experiment and Bayesian optimisation algorithm approaches to method development for the green analysis by supercritical fluid chromatography of a pharmaceutical ingredient.

During drug development, chromatography is frequently used for purity and stability testing of both drug substance and drug product. Reversed phase liquid chromatography (RPLC) is one of the most widely used methodologies due to its wide scope of application. In the later stages of drug development, the specified impurities and degradation products that define the critical quality attribute of the final API, also known as Key Predictive Sample Set (KPSS), are usually well defined and controlled.

Transmission potential of vaccinated and unvaccinated persons infected with the SARS-CoV-2 Delta variant in a federal prison, July-August 2021.

Background: The extent to which vaccinated persons who become infected with SARS-CoV-2 contribute to transmission is unclear. During a SARS-CoV-2 Delta variant outbreak among incarcerated persons with high vaccination rates in a federal prison, we assessed markers of viral shedding in vaccinated and unvaccinated persons.

Methods: Consenting incarcerated persons with confirmed SARS-CoV-2 infection provided mid-turbinate nasal specimens daily for 10 consecutive days and reported symptom data via questionnaire.

Predicting the structural basis of targeted protein degradation by integrating molecular dynamics simulations with structural mass spectrometry.

Targeted protein degradation (TPD) is a promising approach in drug discovery for degrading proteins implicated in diseases. A key step in this process is the formation of a ternary complex where a heterobifunctional molecule induces proximity of an E3 ligase to a protein of interest (POI), thus facilitating ubiquitin transfer to the POI. In this work, we characterize 3 steps in the TPD process.

Effect of Biofumigation on Population Densities of spp. and spp. and Potato Yield in Eastern Canada.

Biofumigation has been proposed as an alternative to soil fumigation to manage soil-borne diseases including potato early dying disease complex (PED). This study examined the potential of using brown mustard () biofumigation to manage PED under rain-fed potato production in New Brunswick, Canada in two trials between 2017 and 2020 in comparison with chloropicrin fumigation and a conventional barley rotation. Biofumigation increased yield in one trial, but not in a second trial where the potato crop experienced severe drought, whereas chloropicrin fumigation increased yield in both trials.

Creating Maps of the Ligand Binding Landscape for Kinetics-Based Drug Discovery.

Simulations of ligand-protein interactions can be very useful for drug design and to gain biological insight. Full pathways of ligand-protein binding can be used to get information about ligand binding transition states, which form the rate-limiting step of the binding and release processes. However, these simulations are typically limited by the presence of large energy barriers that separate stable poses of interest.

Membrane-Mediated Ligand Unbinding of the PK-11195 Ligand from TSPO.

The translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is of longstanding medical interest as both a biomarker for neuroinjury and a potential drug target for neuroinflammation and other disorders. Recently, it was shown that ligand residence time is a key factor determining steroidogenic efficacy of TSPO-binding compounds. This spurs interest in simulations of (un)binding pathways of TSPO ligands, which could reveal the molecular interactions governing ligand residence time.

On Calculating Free Energy Differences Using Ensembles of Transition Paths.

The free energy of a process is the fundamental quantity that determines its spontaneity or propensity at a given temperature. In particular, the binding free energy of a drug candidate to its biomolecular target is used as an objective quantity in drug design. Recently, binding kinetics-rates of association ( ) and dissociation ( )-have also demonstrated utility for their ability to predict efficacy and in some cases have been shown to be more predictive than the binding free energy alone.

Predicting ligand binding affinity using on- and off-rates for the SAMPL6 SAMPLing challenge.

Interest in ligand binding kinetics has been growing rapidly, as it is being discovered in more and more systems that ligand residence time is the crucial factor governing drug efficacy. Many enhanced sampling methods have been developed with the goal of predicting ligand binding rates ([Formula: see text]) and/or ligand unbinding rates ([Formula: see text]) through explicit simulation of ligand binding pathways, and these methods work by very different mechanisms. Although there is not yet a blind challenge for ligand binding kinetics, here we take advantage of experimental measurements and rigorously computed benchmarks to compare estimates of [Formula: see text] calculated as the ratio of two rates: [Formula: see text].

Genetic analysis of Black Tiger shrimp (Penaeus monodon) across its natural distribution range reveals more recent colonization of Fiji and other South Pacific islands.

The Black Tiger shrimp (Penaeus monodon) has a natural distribution range from East Africa to the South Pacific Islands. Although previous studies of Indo-Pacific P. monodon have found populations from the Indian Ocean and Australasia to differ genetically, their relatedness to South Pacific shrimp remains unknown.

A genomics-informed, SNP association study reveals FBLN1 and FABP4 as contributing to resistance to fleece rot in Australian Merino sheep.

Background: Fleece rot (FR) and body-strike of Merino sheep by the sheep blowfly Lucilia cuprina are major problems for the Australian wool industry, causing significant losses as a result of increased management costs coupled with reduced wool productivity and quality. In addition to direct effects on fleece quality, fleece rot is a major predisposing factor to blowfly strike on the body of sheep. In order to investigate the genetic drivers of resistance to fleece rot, we constructed a combined ovine-bovine cDNA microarray of almost 12,000 probes including 6,125 skin expressed sequence tags and 5,760 anonymous clones obtained from skin subtracted libraries derived from fleece rot resistant and susceptible animals.

Differential expression of genes encoding anti-oxidant enzymes in Sydney rock oysters, Saccostrea glomerata (Gould) selected for disease resistance.

Sydney rock oysters (Saccostrea glomerata) selectively bred for disease resistance (R) and wild-caught control oysters (W) were exposed to a field infection of disseminating neoplasia. Cumulative mortality of W oysters (31.7%) was significantly greater than R oysters (0.