Roger Nathan

Paleo-Eskimo mtDNA Genome Reveals Matrilineal Discontinuity in Greenland

The Paleo-Eskimo Saqqaq and Independence I cultures, documented from archaeological remains in Northern Canada and Greenland, represent the earliest human expansion into the New Worlds northern extremes. However, their origin and genetic relationship to later cultures are unknown. We sequenced a mitochondrial genome from a Paleo-Eskimo human by using 3400-to 4500-year-old frozen hair excavated from an early Greenlandic Saqqaq settlement. The sample is distinct from modern Native Americans and Neo-Eskimos, falling within haplogroup D2a1, a group previously observed among modern Aleuts and Siberian Sireniki Yuit. This result suggests that the earliest migrants into the New Worlds northern extremes derived from populations in the Bering Sea area and were not directly related to Native Americans or the later Neo-Eskimos that replaced them.

Chemically amplified photoresist for high resolution autoradiography in targeted radiotherapy.

Evaluation of the intracellular distribution of radionuclides used for targeted radiotherapy (tRT) is essential for accurate dosimetry. Therefore, a direct and quantitative method for subcellular micro-autoradiography using radiation sensitive polymers (PMMA, UV1116 and AZ40XT) was developed. The electron exposure dose in radio-labelled cells due to Auger and internal conversion (IC) electron emissions of indium (¹¹¹In), a radionuclide currently used for tRT, was calculated using Monte Carlo (MC) simulation. Electron beam lithography using pre-defined exposure doses was used to calibrate the resist response. The topography of the exposed and developed resists was analysed with atomic force microscopy (AFM) and the resulting pattern depth was related to a specific exposure dose. UV1116 exhibited the best contrast as compared to AZ40XT and PMMA, while AZ40XT exhibited the highest sensitivity at low doses (<10 μC/cm²). AFM analysis of the exposure pattern from radio-labelled cells and nuclei in UV1116 revealed a non-uniform distribution of ¹¹¹In-EGF in the cell and nucleus, consistent with less well-resolved data from confocal microscopy and micro-autoradiography.

Photoresists as a high spatial resolution autoradiography substrate for quantitative mapping of intra- and sub-cellular distribution of Auger electron emitting radionuclides

Abstract Purpose: To explore poly(methyl methacrylate) (PMMA950) as an autoradiography substrate. Materials and methods: PMMA950 was spin coated onto a silicon substrate. Resists were exposed to either a 25 or 50 keV electron beam (e-beam) with fluences of 0.1–33.6 μC/cm2. The resulting patterns were analyzed by atomic force microscopy (AFM). The dependence of pattern sensitivity and resolution on resist thickness, development time and electron energy was evaluated and correlated with Monte Carlo (MC) modeling. Conventional micro-autoradiography (MAR) images were compared to AFM images of photoresist patterns obtained following exposure from 111In-diethylenetriaminepentaacetic acid (DTPA)-human epidermal growth factor (hEGF) (4–6 MBq/μg, 40 nM DTPA-hEGF)-treated human breast cancer cells MDA-MB-468. Results: MC simulation results confirmed the similarity of particle transport in PMMA950 exposed to either an 111In point source or a 25 keV e-beam. Sensitivity was inversely related to resist thickness. Development conditions of the resists greatly affected image quality. Sensitivity of PMMA950 was similar to the UVIII™ resist (consisting of a copolymer of 4-hydroxystyrene and t- butylacrylate) at low electron fluence for both 25 and 50 keV e-beam exposure. AFM evaluation of the exposure patterns from 111In-DTPA-hEGF treated cells and nuclei provides more detailed information in comparison with that from MAR. Conclusions: Photoresist autoradiography can provide information on both the distribution of radiation sources and their strengths within a biological sample; however, the choice of photoresist material and processing conditions greatly affects the outcome.