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"Thor, Brad"
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Disgraceful council
To paraphrase an article we read recently, Chicago was once famous for its scrappy support of capitalism and individual rights, but the slow creep of socialism is transforming it into a highly regulated paternalist state where what you eat, where you shop and how you run your business are all up for grabs.
Newspaper Article
The Lions of Lucerne : a thriller
When a group of Secret Service agents is massacred in Utah and the president of the United States is abducted, surviving agent Scot Harvath vows to avenge his murdered colleagues and find the kidnappers.
Book
Spymaster : a thriller
\"Across Europe, a secret organization has begun attacking diplomats. Back in the United States, a foreign ally demands the identity of a highly placed covert asset. In the balance hang the ingredients for all-out war. With his mentor out of the game, counterterrorism operative Scot Harvath must take on the role he has spent his career avoiding. But, as with everything else he does, he intends to rewrite the rules-- all of them\"-- Provided by publisher.
Book
Seasonal Climate Variation and Caribou Availability
Livelihood systems that depend on mobile resources must constantly adapt to change. For people living in permanent settlements, environmental changes that affect the distribution of a migratory species may reduce the availability of a primary food source, with the potential to destabilize the regional social-ecological system. Food security for Arctic indigenous peoples harvesting barren ground caribou (Rangifer tarandus granti) depends on movement patterns of migratory herds. Quantitative assessments of physical, ecological, and social effects on caribou distribution have proven difficult because of the significant interannual variability in seasonal caribou movement patterns. We developed and evaluated a modeling approach for simulating the distribution of a migratory herd throughout its annual cycle over a multiyear period. Beginning with spatial and temporal scales developed in previous studies of the Porcupine Caribou Herd of Canada and Alaska, we used satellite collar locations to compute and analyze season-by-season probabilities of movement of animals between habitat zones under two alternative weather conditions for each season. We then built a set of transition matrices from these movement probabilities, and simulated the sequence of movements across the landscape as a Markov process driven by externally imposed seasonal weather states. Statistical tests showed that the predicted distributions of caribou were consistent with observed distributions, and significantly correlated with subsistence harvest levels for three user communities. Our approach could be applied to other caribou herds and could be adapted for simulating the distribution of other ungulates and species with similarly large interannual variability in the use of their range.
Journal Article
Cytocipher determines significantly different populations of cells in single cell RNA-seq data
Identification of cell types using single cell RNA-seq (scRNA-seq) is revolutionising the study of multicellular organisms. However, typical scRNA-seq analysis often involves post hoc manual curation to ensure clusters are transcriptionally distinct, which is time-consuming, error-prone, and irreproducible. To overcome these obstacles, we developed Cytocipher, a bioinformatics method and scverse compatible software package that statistically determines significant clusters. Application of Cytocipher to normal tissue, development, disease, and large-scale atlas data reveals the broad applicability and power of Cytocipher to generate biological insights in numerous contexts. This included the identification of cell types not previously described in the datasets analyzed, such as CD8+ T cell subtypes in human peripheral blood mononuclear cells; cell lineage intermediate states during mouse pancreas development; and subpopulations of luminal epithelial cells over-represented in prostate cancer. Cytocipher also scales to large datasets with high test performance, as shown by application to the Tabula Sapiens Atlas representing >480,000 cells. Cytocipher is a novel and generalisable method that statistically determines transcriptionally distinct and programmatically reproducible clusters from single cell data. Cytocipher is available at https://github.com/BradBalderson/Cytocipher. Competing Interest Statement The authors have declared no competing interest. Footnotes * Added application to prostate cancer and Tabula Sapiens Atlas; Additional supplemental to benchmark methodological decision.
Paper
Selective Requirement for Polycomb Repressor Complex 2 in the Generation of Specific Hypothalamic Neuronal Sub-types
The hypothalamus displays staggering cellular diversity, chiefly established during embryogenesis by the interplay of several signalling pathways and a battery of transcription factors. However, the contribution of epigenetic cues to hypothalamus development remains unclear. We mutated the Polycomb Repressor Complex 2 gene Eed in the developing mouse hypothalamus, which resulted in the loss of H3K27me3; a fundamental epigenetic repressor mark. This triggered ectopic expression of posteriorly expressed regulators (e.g., Hox homeotic genes), upregulation of cell cycle inhibitors and reduced proliferation. Surprisingly, despite these effects, single cell transcriptomic analysis revealed that the majority of neuronal subtypes were still generated in Eed mutants. However, we observed an increase in Glutamatergic/GABAergic double-positive cells, as well as loss/reduction of dopamine, Hypocretin/Orexin and Tac2 neurons. These findings indicate that many aspects of the hypothalamic gene regulatory flow can proceed without the key H3K27me3 epigenetic repressor mark, and points to a unique sensitivity of particular neuronal sub-types to a disrupted epigenomic landscape.
Paper