Macrocyclization as a Strategy for Kinetic Solubility Improvement: A Comparative Analysis of Matched Molecular Pairs.

In recent years, rationally designed macrocycles have emerged as promising therapeutic modalities for challenging drug targets. Macrocycles can improve affinity, selectivity, and pharmacokinetic (PK) parameters, possibly via providing semirigid, preorganized scaffolds. Nevertheless, how macrocyclization affects PK-relevant properties is still poorly understood.

Temporal and regional X-linked gene reactivation in the mouse germline reveals site-specific retention of epigenetic silencing.

Random X-chromosome inactivation is a hallmark of female mammalian somatic cells. This epigenetic mechanism, mediated by the long noncoding RNA Xist, occurs in the early embryo and is stably maintained throughout life, although inactivation is lost during primordial germ cell (PGC) development. Using a combination of single-cell allele-specific RNA sequencing and low-input chromatin profiling on developing mouse PGCs, we provide a detailed map of X-linked gene reactivation.

Advantages and disadvantages of current human enteric virus surrogates in soils and aquifers.

Groundwater is one of the main sources of drinking water, thus, human enteric viruses in groundwater could pose safety risks. Many enteric viruses enter drinking water sources through irrigation or recharge of contaminated water. It is therefore advised to test the potential transport risk with harmless surrogates before wastewater or recycled water is used for irrigation or groundwater recharge.

Developing a cost-effective and efficient safety case management solution for data coordinating center projects.

A centralized safety function can support multiple clinical trials and provide efficient, standardized processes for the management of serious adverse events. From 2017 to 2022, the centralized safety desk used pharmacovigilance software compliant with FDA regulations, including 21 CFR Part 11. This software assisted with processing safety cases for regulated clinical trials, including allowing capture of event data, and provided process flow management, documentation storage, and transmission of safety reports to FDA.

Holding up the mirror: The role of teacher educators and syllabi in perpetuating or disrupting inequity.

This blended pilot-empirical and theoretical manuscript documents a reflective journey undertaken by a group of early childhood teacher educators located across different regions of the United States as they examined their course design, materials, and syllabi construction. Grounded in reflective practice, intersectionality, and critical pedagogy, their collaborative endeavor necessitated profound self-examination and recognition of oppressive structures inherent within the field and reproduced throughout course syllabi, thereby perpetuating societal inequities inside and outside the classroom context. Their iterative, evolving effort resembled a reflective consultation group, marked by continuous self-reflection, challenging assumptions, and transforming actions, vividly portrayed in their vignettes.