Mathematical geology最新文献

Cystic fibrosis transmembrane conductance regulator (CFTR) channel gating is predominantly regulated by protein kinase A (PKA)-dependent phosphorylation. In addition to regulating CFTR channel activity, PKA phosphorylation is also involved in enhancing CFTR trafficking and mediating conformational changes at the interdomain interfaces of the protein. The major cystic fibrosis (CF)-causing mutation is the deletion of phenylalanine at position 508 (F508del); it causes many defects that affect CFTR trafficking, stability, and gating at the cell surface. Due to the multiple roles of PKA phosphorylation, there is growing interest in targeting PKA-dependent signaling for rescuing the trafficking and functional defects of F508del-CFTR. This review will discuss the effects of PKA phosphorylation on wild-type CFTR, the consequences of CF mutations on PKA phosphorylation, and the development of therapies that target PKA-mediated signaling.

The analysis of health data and putative covariates, such as environmental, socio-economic, behavioral or demographic factors, is a promising application for geostatistics. It presents, however, several methodological challenges that arise from the fact that data are typically aggregated over irregular spatial supports and consist of a numerator and a denominator (i.e. population size). This paper presents an overview of recent developments in the field of health geostatistics, with an emphasis on three main steps in the analysis of areal health data: estimation of the underlying disease risk, detection of areas with significantly higher risk, and analysis of relationships with putative risk factors. The analysis is illustrated using age-adjusted cervix cancer mortality rates recorded over the 1970-1994 period for 118 counties of four states in the Western USA. Poisson kriging allows the filtering of noisy mortality rates computed from small population sizes, enhancing the correlation with two putative explanatory variables: percentage of habitants living below the federally defined poverty line, and percentage of Hispanic females. Area-to-point kriging formulation creates continuous maps of mortality risk, reducing the visual bias associated with the interpretation of choropleth maps. Stochastic simulation is used to generate realizations of cancer mortality maps, which allows one to quantify numerically how the uncertainty about the spatial distribution of health outcomes translates into uncertainty about the location of clusters of high values or the correlation with covariates. Last, geographically-weighted regression highlights the non-stationarity in the explanatory power of covariates: the higher mortality values along the coast are better explained by the two covariates than the lower risk recorded in Utah.

This paper presents a methodology to conduct geostatistical variography and interpolation on areal data measured over geographical units (or blocks) with different sizes and shapes, while accounting for heterogeneous weight or kernel functions within those units. The deconvolution method is iterative and seeks the pointsupport model that minimizes the difference between the theoretically regularized semivariogram model and the model fitted to areal data. This model is then used in area-to-point (ATP) kriging to map the spatial distribution of the attribute of interest within each geographical unit. The coherence constraint ensures that the weighted average of kriged estimates equals the areal datum.This approach is illustrated using health data (cancer rates aggregated at the county level) and population density surface as a kernel function. Simulations are conducted over two regions with contrasting county geographies: the state of Indiana and four states in the Western United States. In both regions, the deconvolution approach yields a point support semivariogram model that is reasonably close to the semivariogram of simulated point values. The use of this model in ATP kriging yields a more accurate prediction than a naïve point kriging of areal data that simply collapses each county into its geographic centroid. ATP kriging reduces the smoothing effect and is robust with respect to small differences in the point support semivariogram model. Important features of the point-support semivariogram, such as the nugget effect, can never be fully validated from areal data. The user may want to narrow down the set of solutions based on his knowledge of the phenomenon (e.g., set the nugget effect to zero). The approach presented avoids the visual bias associated with the interpretation of choropleth maps and should facilitate the analysis of relationships between variables measured over different spatial supports.