Blending organic material with municipal solid waste incinerator bottom ash to promote in-situ carbonation in road base.

The use of municipal solid waste incinerator bottom ash for road-base construction is an accepted practice in Europe and Asia, and of growing interest in the US. It is common practice to cure bottom ash by stockpiling it for several weeks before using it in this application. The curing process exposes the bottom ash to atmospheric carbon dioxide, which promotes carbonation, lowering its pH (making it less alkaline), and making many heavy metals less soluble.

Exploring Chronic Drug Effects on Microengineered Human Liver Cultures Using Global Gene Expression Profiling.

Global gene expression profiling is useful for elucidating a drug's mechanism of action on the liver; however, such profiling in rats is not very sensitive for predicting human drug-induced liver injury, while dedifferentiated monolayers of primary human hepatocytes (PHHs) do not permit chronic drug treatment. In contrast, micropatterned cocultures (MPCCs) containing PHH colonies and 3T3-J2 fibroblasts maintain a stable liver phenotype for 4-6 weeks. Here, we used MPCCs to test the hypothesis that global gene expression patterns in stable PHHs can be used to distinguish clinical hepatotoxic drugs from their non-liver-toxic analogs and understand the mechanism of action prior to the onset of overt hepatotoxicity.

MTAP Deletions in Cancer Create Vulnerability to Targeting of the MAT2A/PRMT5/RIOK1 Axis.

Homozygous deletions of p16/CDKN2A are prevalent in cancer, and these mutations commonly involve co-deletion of adjacent genes, including methylthioadenosine phosphorylase (MTAP). Here, we used shRNA screening and identified the metabolic enzyme, methionine adenosyltransferase II alpha (MAT2A), and the arginine methyltransferase, PRMT5, as vulnerable enzymes in cells with MTAP deletion. Metabolomic and biochemical studies revealed a mechanistic basis for this synthetic lethality.

Construction material properties of slag from the high temperature arc gasification of municipal solid waste.

Slag from the high temperature arc gasification (HTAG) of municipal solid waste (MSW) was tested to evaluate its material properties with respect to use as a construction aggregate. These data were compared to previously compiled values for waste to energy bottom ash, the most commonly produced and beneficially used thermal treatment residue. The slag was tested using gradations representative of a base course and a course aggregate.

Establishment of a hepatocyte-kupffer cell coculture model for assessment of proinflammatory cytokine effects on metabolizing enzymes and drug transporters.

Elevated levels of proinflammatory cytokines associated with infection and inflammation can modulate cytochrome P450 enzymes, leading to potential disease-drug interactions and altered small-molecule drug disposition. We established a human-derived hepatocyte-Kupffer cell (Hep:KC) coculture model to assess the indirect cytokine impact on hepatocytes through stimulation of KC-mediated cytokine release and compared this model with hepatocytes alone. Characterization of Hep:KC cocultures showed an inflammation response after treatment with lipopolysaccharide and interleukin (IL)-6 (indicated by secretion of various cytokines).

Bioactivation and toxicity of acetaminophen in a rat hepatocyte micropatterned coculture system.

We have recently shown that primary rat hepatocytes organized in micropatterned cocultures with murine embryonic fibroblasts (HepatoPac™) maintain high levels of liver functions for at least 4 weeks. In this study, rat HepatoPac was assessed for its utility to study chemical bioactivation and associated hepatocellular toxicity. Treatment of HepatoPac cultures with acetaminophen (APAP) over a range of concentrations (0-15 mM) was initiated at 1, 2, 3, or 4 weeks followed by the assessment of morphological and functional endpoints.

SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging.

Genomic instability and alterations in gene expression are hallmarks of eukaryotic aging. The yeast histone deacetylase Sir2 silences transcription and stabilizes repetitive DNA, but during aging or in response to a DNA break, the Sir complex relocalizes to sites of genomic instability, resulting in the desilencing of genes that cause sterility, a characteristic of yeast aging. Using embryonic stem cells, we show that mammalian Sir2, SIRT1, represses repetitive DNA and a functionally diverse set of genes across the mouse genome.

Medicine and spirituality: a simple path to restore compassion in medicine.

Medical science has achieved impressive accomplishments in the diagnosis and treatment of human disease. However, the emphasis on science and technology has created a generation of physicians who find it difficult to relate to their patients about their suffering. Time constraints and economic pressures also add to the challenge of giving meaningful time to patients.