Automated identification of Fos expression

The concentration of Fos, a protein encoded by the immediate-early gene c-fos, provides a measure of synaptic activity that may not parallel the electrical activity of neurons. Such a measure is important for the difficult problem of identifying dynamic properties of neuronal circuitries activated by a variety of stimuli and behaviours. We employ two-stage statistical pattern recognition to identify cellular nuclei that express Fos in two-dimensional sections of rat forebrain after administration of antipsychotic drugs. In stage one, we distinguish dark-stained candidate nuclei from image background by a thresholding algorithm and record size and shape measurements of these objects. In stage two, we compare performance of linear and quadratic discriminants, nearest-neighbour and artificial neural network classifiers that employ functions of these measurements to label candidate objects as either Fos nuclei, two touching Fos nuclei or irrelevant background material. New images of neighbouring brain tissue serve as test sets to assess generalizability of the best derived classification rule, as determined by lowest cross-validation misclassification rate. Three experts, two internal and one external, compare manual and automated results for accuracy assessment. Analyses of a subset of images on two separate occasions provide quantitative measures of inter- and intra-expert consistency. We conclude that our automated procedure yields results that compare favourably with those of the experts and thus has potential to remove much of the tedium, subjectivity and irreproducibility of current Fos identification methods in digital microscopy

APOCALYPSE NO: Population Aging and the Future of Health Care Systems

Illness increases with age. All else equal, an older population has greater needs for health care. This logic has led to dire predictions of skyrocketing costs-- "apocalyptic demography". Yet numerous studies have shown that aging effects are relatively small, and all else is not equal. Cost projections rest on specific assumptions about trends in age- specific morbidity and health care use that are far from self-evident. Sharply contrasting assumptions, for example, are made by Fries, who foresees a "compression of morbidity" and falling needs. Long term trends in health care use in British Columbia show minimal effects of population aging, but major effects, up and down, from changes in age- specific use patterns. Why then is the demographic apocalypse story so persistent, despite numerous contrary studies? It serves identifiable economic interests.aging, health care utilization, demography, health care financing

Number--conserving model for boson pairing

An independent pair ansatz is developed for the many body wavefunction of dilute Bose systems. The pair correlation is optimized by minimizing the expectation value of the full hamiltonian (rather than the truncated Bogoliubov one) providing a rigorous energy upper bound. In contrast with the Jastrow model, hypernetted chain theory provides closed-form exactly solvable equations for the optimized pair correlation. The model involves both condensate and coherent pairing with number conservation and kinetic energy sum rules satisfied exactly and the compressibility sum rule obeyed at low density. We compute, for bulk boson matter at a given density and zero temperature, (i) the two--body distribution function, (ii) the energy per particle, (iii) the sound velocity, (iv) the chemical potential, (v) the momentum distribution and its condensate fraction and (vi) the pairing function, which quantifies the ODLRO resulting from the structural properties of the two--particle density matrix. The connections with the low--density expansion and Bogoliubov theory are analyzed at different density values, including the density and scattering length regime of interest of trapped-atoms Bose--Einstein condensates. Comparison with the available Diffusion Monte Carlo results is also made.Comment: 21 pages, 12 figure

An assessment of Evans' unified field theory I

Evans developed a classical unified field theory of gravitation and electromagnetism on the background of a spacetime obeying a Riemann-Cartan geometry. This geometry can be characterized by an orthonormal coframe theta and a (metric compatible) Lorentz connection Gamma. These two potentials yield the field strengths torsion T and curvature R. Evans tried to infuse electromagnetic properties into this geometrical framework by putting the coframe theta to be proportional to four extended electromagnetic potentials A; these are assumed to encompass the conventional Maxwellian potential in a suitable limit. The viable Einstein-Cartan(-Sciama-Kibble) theory of gravity was adopted by Evans to describe the gravitational sector of his theory. Including also the results of an accompanying paper by Obukhov and the author, we show that Evans' ansatz for electromagnetism is untenable beyond repair both from a geometrical as well as from a physical point of view. As a consequence, his unified theory is obsolete.Comment: 39 pages of latex, modified because of referee report, mistakes and typos removed, partly reformulated, taken care of M.W.Evans' rebutta

Extraction of the πNN\pi NN coupling constant from NN scattering data

We reexamine Chew's method for extracting the $\pi NN$ coupling constant from np differential cross section measurements. Values for this coupling are extracted below 350 MeV, in the potential model region, and up to 1 GeV. The analyses to 1~GeV have utilized 55 data sets. We compare these results to those obtained via $\chi^2$ mapping techniques. We find that these two methods give consistent results which are in agreement with previous Nijmegen determinations.Comment: 12 pages of text plus 2 figures. Revtex file and postscript figures available via anonymous FTP at ftp://clsaid.phys.vt.edu/pub/n

Inhibition of glycolysis modulates prednisolone resistance in acute lymphoblastic leukemia cells

Treatment failure in pediatric acute lymphoblastic leukemia (ALL) is related to cellular resistance to glucocorticoids (eg, prednisolone). Recently, we demonstrated that genes associated with glucose metabolism are differentially expressed between prednisolone-sensitive and prednisolone-resistant precursor B-lineage leukemic patients. Here, we show that prednisolone resistance is associated with increased glucose consumption and that inhibition of glycolysis sensitizes prednisolone-resistant ALL cell lines to glucocorticoids. Treatment of prednisolone-resistant Jurkat and Molt4 cells with 2-deoxy-D-glucose (2-DG), lonidamine (LND), or3-bromopyruvate (3-BrPA) increased the in vitro sensitivity to glucocorticoids, while treatment of the prednisolone-sensitive cell lines Tom-1 and RS4; 11 did not influence drug cyto-toxicity. This sensitizing effect of the glycolysis inhibitors in glucocorticoid-resistant ALL cells was not found for other classes of antileukemic drugs (ie, vincris-tine and daunorubicin). Moreover, down-regulation of the expression of GAPDH by RNA interference also sensitized to prednisolone, comparable with treatment with glycolytic inhibitors. Importantly, the ability of 2-DG to reverse glucocorticoid resistance was not limited to cell lines, but was also observed in isolated primary ALL cells from patients. Together, these findings indicate the importance of the glycolytic pathway in glucocorticoid resistance in ALL and suggest that targeting glycolysis is a viable strategy for modulating prednisolone resistance in ALL

Search for an annual modulation of dark-matter signals with a germanium spectrometer at the Sierra Grande Laboratory

Data collected during three years with a germanium spectrometer at the Sierra Grande underground laboratory have been analyzed for distinctive features of annual modulation of the signal induced by WIMP dark matter candidates. The main motivation for this analysis was the recent suggestion by the DAMA/NaI Collaboration that a yearly modulation signal could not be rejected at the 90% confidence level when analyzing data obtained with a high-mass low-background scintillator detector. We performed two different analyses of the data: First, the statistical distribution of modulation-significance variables (expected from an experiment running under the conditions of Sierra Grande) was compared with the same variables obtained from the data. Second, the data were analyzed in energy bins as an independent check of the first result and to allow for the possibility of a crossover in the expected signal. In both cases no statistically significant deviation from the null result was found, which could support the hypothesis that the data contain a modulated component. A plot is also presented to enable the comparison of these results to those of the DAMA collaboration.Comment: New version accepted by Astroparticle Physics. Changes suggested by the referee about the theoretical prediction of rates are included. Conclusions remain unaffected. 14 pages, LaTeX, 7 figures. Uses epsfig macr

Asparagine synthetase expression is linked with L-asparaginase resistance in TEL-AML1-negative but not TEL-AML1-positive pediatric acute lymphoblastic leukemia

Resistance to L-asparaginase in leukemic cells may be caused by an elevated cellular expression of asparagine synthetase (AS). Previously, we reported that high AS expression did not correlate to L-asparaginase resistance in TEL-AML1-positive B-lineage acute lymphoblastic leukemia (ALL). In the present study we confirmed this finding in TEL-AML1-positive patients (n = 28) using microarrays. In contrast, 35 L-asparaginase-resistant TEL-AML1-negative B-lineage ALL patients had a significant 3.5-fold higher AS expression than 43 sensitive patients (P < .001). Using real-time quantitative polymerase chain reaction (RTQ-PCR), this finding was confirmed in an independent group of 39 TEL-AML1-negative B-lineage ALL patients (P = .03). High expression of AS was associated with poor prognosis (4-year probability of disease-free survival [pDFS] 58% +/- 11%) compared with low expression (4-year pDFS 83% +/- 7%; P = .009). We conclude that resistance to l-asparaginase and relapse risk are associated with high expression of AS in TEL-AML1-negative but not TEL-AML1-positive B-lineage ALL

Cell shape analysis of random tessellations based on Minkowski tensors

To which degree are shape indices of individual cells of a tessellation characteristic for the stochastic process that generates them? Within the context of stochastic geometry and the physics of disordered materials, this corresponds to the question of relationships between different stochastic models. In the context of image analysis of synthetic and biological materials, this question is central to the problem of inferring information about formation processes from spatial measurements of resulting random structures. We address this question by a theory-based simulation study of shape indices derived from Minkowski tensors for a variety of tessellation models. We focus on the relationship between two indices: an isoperimetric ratio of the empirical averages of cell volume and area and the cell elongation quantified by eigenvalue ratios of interfacial Minkowski tensors. Simulation data for these quantities, as well as for distributions thereof and for correlations of cell shape and volume, are presented for Voronoi mosaics of the Poisson point process, determinantal and permanental point processes, and Gibbs hard-core and random sequential absorption processes as well as for Laguerre tessellations of polydisperse spheres and STIT- and Poisson hyperplane tessellations. These data are complemented by mechanically stable crystalline sphere and disordered ellipsoid packings and area-minimising foam models. We find that shape indices of individual cells are not sufficient to unambiguously identify the generating process even amongst this limited set of processes. However, we identify significant differences of the shape indices between many of these tessellation models. Given a realization of a tessellation, these shape indices can narrow the choice of possible generating processes, providing a powerful tool which can be further strengthened by density-resolved volume-shape correlations.Comment: Chapter of the forthcoming book "Tensor Valuations and their Applications in Stochastic Geometry and Imaging" in Lecture Notes in Mathematics edited by Markus Kiderlen and Eva B. Vedel Jense