Modeling the clonal heterogeneity of stem cells

Recent experimental studies suggest that tissue stem cell pools are composed of functionally diverse clones. Metapopulation models in ecology concentrate on collections of populations and their role in stabilizing coexistence and maintaining selected genetic or epigenetic variation. Such models are characterized by expansion and extinction of spatially distributed populations. We develop a mathematical framework derived from the multispecies metapopulation model of Tilman et al (1994) to study the dynamics of heterogeneous stem cell metapopulations. In addition to normal stem cells, the model can be applied to cancer cell populations and their response to treatment. In our model disturbances may lead to expansion or contraction of cells with distinct properties, reflecting proliferation, apoptosis, and clonal competition. We first present closed-form expressions for the basic model which defines clonal dynamics in the presence of exogenous global disturbances. We then extend the model to include disturbances which are periodic and which may affect clones differently. Within the model framework, we propose a method to devise an optimal strategy of treatments to regulate expansion, contraction, or mutual maintenance of cells with specific properties

Immobilization of 293 cells using porous support particles for adenovirus vector production

Adenovirus vector production by anchorage-independent 293 cells immobilized using porous biomass support particles (BSPs) was investigated in static and shake-flask cultures for efficient large-scale production of adenovirus vectors for gene therapy applications. The density of cells immobilized within BSPs was evaluated by measuring their WST-8 (2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt) reduction activity. In shake-flask culture, 293-F cells, which were adapted to serum-free suspension culture, were not successfully retained within reticulated polyvinyl formal (PVF) resin BSPs (2 × 2 × 2 mm cubes) with matrices of relatively small pores (pore diameter 60 μm). When the BSPs were coated with a cationic polymer polyethyleneimine, a high cell density of more than 107 cells cm−3-BSP was achieved in both static and shake-flask cultures with regular replacement of the culture medium. After infection with an adenovirus vector carrying the enhanced green fluorescent protein gene (Ad EGFP), the specific Ad EGFP productivity of the immobilized cells was comparable to the maximal productivity of non-immobilized 293-F cells by maintaining favorable conditions in the culture environment

The Alpha Magnetic Spectrometer (AMS) on the international space station: Part I - results from the test flight on the space shuttle

The Alpha Magnetic Spectrometer (AMS) was flown on the space shuttle Discovery during flight STS-91 (June 1998) in a 51.7° orbit at altitudes between 320 and.A search for antihelium nuclei in the rigidity range 1–was performed. No antihelium nuclei were detected at any rigidity. An upper limit on the flux ratio of antihelium to helium of <1.1×10−6 was obtained.The high energy proton, electron, positron, helium, antiproton and deuterium spectra were accurately measured.For each particle and nuclei two distinct spectra were observed: a higher energy spectrum and a substantial second spectrum. Positrons in the second spectrum were found to be much more abundant than electrons. Tracing particles from the second spectra shows that most of them travel for an extended period of time in the geomagnetic field, and that the positive particles (p and e+) and negative ones (e−) originate from two complementary geographic regions. The second helium spectrum flux over the energy range 0.1–was measured to be . Over 90 percent of the helium flux was determined to be at the 90% confidence level. (Elsevier