Publications

We present a commercially-available, fully-automated, offline chromatography method capable of simultaneously purifying both Ca and Sr for stable and radiogenic isotope analysis. The method features effective purification and mutual separation of Ca and Sr from complex matrixes using a single, highly-reusable chromatographic column. Low carryover combined with high yield for multiple extractions indicates the column can be reused for at least 200 samples. Accurate and precise stable and radiogenic isotope data are presented for BCR-2 basalt, NIST-1400 bone ash, IAPSO seawater, and an in-house llama bone standard (CUE-0001). The Sr-Ca method was designed to accommodate a wide variety of sample types, including carbonates, bones, and teeth; silicate rocks and sediments; fresh and marine waters; and biological samples such as blood and urine. The system is highly adaptable and capable of processing up to 60 samples per run at a rate of 32 samples per day on a single chromatographic column during unattended operation.

We use a microfabricated ecology with a doxorubicin gradient and population fragmentation to produce a strong Darwinian selective pressure that drives forward the rapid emergence of doxorubicin resistance in multiple myeloma (MM) cancer cells. RNA sequencing of the resistant cells was used to examine (i) emergence of genes with high de novo substitution densities (i.e., hot genes) and (ii) genes never substituted (i.e., cold genes). The set of cold genes, which were 21% of the genes sequenced, were further winnowed down by examining excess expression levels. Both the most highly substituted genes and the most highly expressed never-substituted genes were biased in age toward the most ancient of genes. This would support the model that cancer represents a revision back to ancient forms of life adapted to high fitness under extreme stress, and suggests that these ancient genes may be targets for cancer therapy.

Several authors have argued that causes differ in the degree to which they are ‘specific’ to their effects. Woodward has used this idea to enrich his influential interventionist theory of causal explanation. Here we propose a way to measure causal specificity using tools from information theory. We show that the specificity of a causal variable is not well defined without a probability distribution over the states of that variable. We demonstrate the tractability and interest of our proposed measure by measuring the specificity of coding DNA and other factors in a simple model of the production of mRNA.

This review explores the incessant evolutionary interaction and co-development between immune system evolution and somatic evolution, to put it into context with the short, over 60-year, detailed human study of this extraordinary protective system. Over millions of years, the evolutionary development of the immune system in most species has been continuously shaped by environmental interactions between microbes, and aberrant somatic cells, including malignant cells. Not only has evolution occurred in somatic cells to adapt to environmental pressures for survival purposes, but the immune system and its function has been successively shaped by those same evolving somatic cells and microorganisms through continuous adaptive symbiotic processes of progressive simultaneous immunological and somatic change to provide what we observe today. Indeed, the immune system as an environmental influence has also shaped somatic and microbial evolution. Although the immune system is tuned to primarily controlling microbiological challenges for combatting infection, it can also remove damaged and aberrant cells, including cancer cells to induce long-term cures. Our knowledge of how this occurs is just emerging. Here we consider the connections between immunity, infection and cancer, by searching back in time hundreds of millions of years to when multi-cellular organisms first began. We are gradually appreciating that the immune system has evolved into a truly brilliant and efficient protective mechanism, the importance of which we are just beginning to now comprehend. Understanding these aspects will likely lead to more effective cancer and other therapies.