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Sökning: WFRF:(Milgrom R) > Naturvetenskap

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1.
  • Maxwell, Christopher A., et al. (författare)
  • Interplay between BRCA1 and RHAMM Regulates Epithelial Apicobasal Polarization and May Influence Risk of Breast Cancer
  • 2011
  • Ingår i: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885 .- 1544-9173. ; 9:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio ((w)HR) = 1.09 (95% CI 1.02-1.16), p(trend) = 0.017; and n = 3,965, (w)HR = 1.04 (95% CI 0.94-1.16), p(trend) = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM.
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2.
  • Lu, Q., et al. (författare)
  • Tracking Initially Unresolved Thrusting Objects Using an Optical Sensor
  • 2018
  • Ingår i: IEEE Transactions on Aerospace and Electronic Systems. - 1557-9603 .- 0018-9251. ; 54:2, s. 794-807
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper considers the problem of estimating the three-dimensional states of a salvo of thrusting/ballistic endo-atmospheric objects using two-dimensional (2-D) Cartesian measurements from the focal plane array (FPA) of a single fixed optical sensor. Since the initial separations in the FP are smaller than the resolution of the sensor, there are merged FP measurements, compounding the usual false-alarm and missed-detection uncertainty. We present a two-step methodology. First, we assume a Wiener process acceleration model for the motion of the images of the objects in the optical sensor's FPA. We model the merged measurements with increased variance, and thence employ a multi-Bernoulli (MB) filter using the 2-D measurements in the FPA. Second, using the set of associated measurements for each confirmed MB track, we formulate a parameter estimation problem, whose maximum likelihood solution can be obtained via numerical search and can be used for impact point prediction. Simulation results illustrate the performance of the proposed method.
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