A Diffusion-like Process Accommodates New Crypts During Clonal Expansion in Human Colonic Epithelium.

Background & Aims: Colorectal cancer (CRC) is thought to arise when the cumulative mutational burden within colonic crypts exceeds a certain threshold that leads to clonal expansion and ultimately neoplastic transformation. Therefore, quantification of the fixation and subsequent expansion of somatic mutations in normal epithelium is key to understanding colorectal cancer initiation. The aim of the present study was to determine how advantaged expansions can be accommodated in the human colon.

Spatiotemporal analysis of human intestinal development at single-cell resolution.

Development of the human intestine is not well understood. Here, we link single-cell RNA sequencing and spatial transcriptomics to characterize intestinal morphogenesis through time. We identify 101 cell states including epithelial and mesenchymal progenitor populations and programs linked to key morphogenetic milestones.

Heterogeneity in clone dynamics within and adjacent to intestinal tumours identified by Dre-mediated lineage tracing.

Somatic models of tissue pathology commonly use induction of gene-specific mutations in mice mediated by spatiotemporal regulation of Cre recombinase. Subsequent investigation of the onset and development of disease can be limited by the inability to track changing cellular behaviours over time. Here, a lineage-tracing approach based on ligand-dependent activation of Dre recombinase that can be employed independently of Cre is described.

Optimal control for disease vector management in SIT models: an integrodifference equation approach.

Vector-borne diseases are a major public health concern inflicting high levels of disease morbidity and mortality. Vector control is one of the principal methods available to manage infectious disease burden. One approach, releasing modified vectors (such as sterile or GM mosquitoes) Into the wild population has been suggested as an effective method of vector control.

Ecological effects on underdominance threshold drives for vector control.

Underdominance gene drives are frequency-dependent drives that aim to spread a desired homozygote genotype within a population. When the desired homozygote is released above a threshold frequency, heterozygote fitness disadvantage acts to drive the desired trait to fixation. Underdominance drives have been proposed as a way to control vector-borne disease through population suppression and replacement in a spatially contained and reversible way-benefits that directly address potential safety concerns with gene drives.

Optimal control of malaria: combining vector interventions and drug therapies.

Background: The sterile insect technique and transgenic equivalents are considered promising tools for controlling vector-borne disease in an age of increasing insecticide and drug-resistance. Combining vector interventions with artemisinin-based therapies may achieve the twin goals of suppressing malaria endemicity while managing artemisinin resistance. While the cost-effectiveness of these controls has been investigated independently, their combined usage has not been dynamically optimized in response to ecological and epidemiological processes.

Viscous effects on the attenuation of a plane wave by an acoustic lining in shear flow.

The attenuation of a plane acoustic wave incident on a flat impedance surface in a sheared and viscous fluid is investigated numerically and asymptotically. Predictions of various boundary models of impedance surfaces in shear flow are tested by comparing their predicted reflection coefficient. It is found that viscosity has a significant effect, reducing the reflection of upstream propagating sound while increasing the reflection of cross-stream propagating sound.