Acute toxicity of methyl isocyanate in mammals. II. Induction of hyperglycemia, lactic acidosis, uraemia, and hypothermia in rats

When rats were administered methyl isocyanate (MIC) by inhalation or subcutaneous route it produced severe hyperglycemia, clinical lactic acidosis, highly elevated plasma urea, and reduced plasma cholinesterase activity with unaltered erythrocytc acetyl cholinesterase activity. Irrespective of the route of administration, MIC also caused severe hypothermia, which was not ameliorated by prior administration of atropine sulphate. Acute toxic effects of MIC are essentially similar by either route except for the intensity of the effect

A Synthesis Methodology for Application-Specific Logic-in-Memory Designs

ABSTRACT For deeply scaled digital integrated systems, the power required for transporting data between memory and logic can exceed the power needed for computation, thereby limiting the efficacy of synthesizing logic and compiling memory independently. Logic-in-Memory (LiM) architectures address this challenge by embedding logic within the memory block to perform basic operations on data locally for specific functions. While custom smart memories have been successfully constructed for various applications, a fully automated LiM synthesis flow enables architectural exploration that has heretofore not been possible. In this paper we present a tool and design methodology for LiM physical synthesis that performs co-design of algorithms and architectures to explore system level trade-offs. The resulting layouts and timing models can be incorporated within any physical synthesis tool. Silicon results shown in this paper demonstrate a 250x performance improvement and 310x energy savings for a data-intensive application example

Global Transcriptional Response to CRISPR/Cas9-AAV6-Based Genome Editing in CD34+ Hematopoietic Stem and Progenitor Cells.

Genome-editing technologies are currently being translated to the clinic. However, cellular effects of the editing machinery have yet to be fully elucidated. Here, we performed global microarray-based gene expression measurements on human CD34+ hematopoietic stem and progenitor cells that underwent editing. We probed effects of the entire editing process as well as each component individually, including electroporation, Cas9 (mRNA or protein) with chemically modified sgRNA, and AAV6 transduction. We identified differentially expressed genes relative to control treatments, which displayed enrichment for particular biological processes. All editing machinery components elicited immune, stress, and apoptotic responses. Cas9 mRNA invoked the greatest amount of transcriptional change, eliciting a distinct viral response and global transcriptional downregulation, particularly of metabolic and cell cycle processes. Electroporation also induced significant transcriptional change, with notable downregulation of metabolic processes. Surprisingly, AAV6 evoked no detectable viral response. We also found Cas9/sgRNA ribonucleoprotein treatment to be well tolerated, in spite of eliciting a DNA damage signature. Overall, this data establishes a benchmark for cellular tolerance of CRISPR/Cas9-AAV6-based genome editing, ensuring that the clinical protocol is as safe and efficient as possible

Increase in Dye:Dendrimer Ratio Decreases Cellular Uptake of Neutral Dendrimers in RAW Cells

Neutral generation 3 poly­(amidoamine) dendrimers were labeled with Oregon Green 488 (G3-OG_n) to obtain materials with controlled fluorophore:dendrimer ratios (n = 1–2), a mixture containing mostly 3 dyes per dendrimer, a mixture containing primarily 4 or more dyes per dendrimer (<i>n</i> = 4+), and a stochastic mixture (<i>n</i> = 4_avg). The UV absorbance of the dye conjugates increased linearly as n increased and the fluorescence emission decreased linearly as n increased. Cellular uptake was studied in RAW cells and HEK 293A cells as a function of the fluorophore:dendrimer ratio (n). The cellular uptake of G3-OG_<i>n</i> (<i>n</i> = 3, 4+, 4_avg) into RAW cells was significantly lower than G3-OG_<i>n</i> (<i>n</i> = 1, 2). The uptake of G3-OG_<i>n</i> (<i>n</i> = 3, 4+, 4_avg) into HEK 293A cells was not significantly different from G3-OG₁. Thus, the fluorophore:dendrimer ratio was observed to change the extent of uptake in the macrophage uptake mechanism but not in the HEK 293A cell. This difference in endocytosis indicates the presence of a pathway in the macrophage that is sensitive to hydrophobicity of the particle