Search Results (4)

There is early evidence of extraocular systemic signals effecting function and morphology in neovascular age-related macular degeneration (nAMD). The prospective, cross-sectional BIOMAC study is an explorative investigation of peripheral blood proteome profiles and matched clinical features to uncover systemic determinacy in nAMD under anti-vascular endothelial growth factor intravitreal therapy (anti-VEGF IVT). It includes 46 nAMD patients stratified by the level of disease control under ongoing anti-VEGF treatment. Proteomic profiles in peripheral blood samples of every patient were detected with LC-MS/MS mass spectrometry. The patients underwent extensive clinical examination with a focus on macular function and morphology. In silico analysis includes unbiased dimensionality reduction and clustering, a subsequent annotation of clinical features, and non-linear models for recognition of underlying patterns. The model assessment was performed using leave-one-out cross validation. The findings provide an exploratory demonstration of the link between systemic proteomic signals and macular disease pattern using and validating non-linear classification models. Three main results were obtained: (1) Proteome-based clustering identifies two distinct patient subclusters with the smaller one (n = 10) exhibiting a strong signature for oxidative stress response. Matching the relevant meta-features on the individual patient’s level identifies pulmonary dysfunction as an underlying health condition in these patients. (2) We identify biomarkers for nAMD disease features with Aldolase C as a putative factor associated with superior disease control under ongoing anti-VEGF treatment. (3) Apart from this, isolated protein markers are only weakly correlated with nAMD disease expression. In contrast, applying a non-linear classification model identifies complex molecular patterns hidden in a high number of proteomic dimensions determining macular disease expression. In conclusion, so far unconsidered systemic signals in the peripheral blood proteome contribute to the clinically observed phenotype of nAMD, which should be examined in future translational research on AMD. Full article

The effects of feeding low-protein (LP) diets and the age and genotype of fattening pigs were evaluated in an N-balance trial. Sixty weaned piglets of two genotypes were allotted to three different diets. Besides the control diets for the crossbred Topigs 20 × DanBred Duroc (TD) and Hungarian Large White (HLW) pigs, two LP diets were fed containing 1.5 (T1.5) and 3% (T3) less dietary protein than the control. The LP diets were supplemented with crystalline lysine, threonine, tryptophan, and methionine to equalize their digestible amino acid contents. Starter diets were fed between 20–30, grower I between 30–40, grower II between 40–80 and finisher between 80–110 kg live weights. Pigs were kept in floor pens, with 10 animals per pen. In all phases, six pigs with similar live weight were placed into individual balance cages and in the frame of a seven-day long balance trial, the daily N-intake, fecal and urinary N-excretion were measured. From the data N-digestibility, the total ammoniacal nitrogen (TAN) and N-retention were calculated. All the investigated main factors, the genotype and age of pigs and the protein content of the diets had significant effects on the N-balance of fattening pigs. The determinacy of the factors depended on the investigated parameter. Fecal N-excretion and N-digestibility were steadier compared with the urinary N-exertion and TAN percentage. N-digestibility increased and the urinary N-excretion decreased when LP diets were fed. The urinary N-decreasing effect of LP diets was not linear. Compared with the control (19.6 gN/day), T1.5 treatment resulted in 14.5, treatment T3 in 12.4 g daily urinary N-excretion. The TAN and the N-retention of HLW pigs were more favorable than those of TD pigs. Based on our results, it can be concluded that the accuracy of the nitrogen and TAN excretion values of pigs, used in the calculation of the national NH₃ inventories, could be improved if the genotype, the more detailed age categories and the different protein levels of feeds are considered. Full article

We model the growth, dispersal and mutation of two phenotypes of a species using reaction–diffusion equations, focusing on the biologically realistic case of small mutation rates. Having verified that the addition of a small linear mutation term to a Lotka–Volterra system limits it to only two steady states in the case of weak competition, an unstable extinction state and a stable coexistence state, we exploit the fact that the spreading speed of the system is known to be linearly determinate to show that the spreading speed is a nonincreasing function of the mutation rate, so that greater mixing between phenotypes leads to slower propagation. We also find the ratio at which the phenotypes occur at the leading edge in the limit of vanishing mutation. Full article

In this paper we define a non-deterministic dynamic neighborhood model. As a special case, a linear neighborhood model is considered. When a non-deterministic neighborhood model functions, it is possible to introduce a restriction on the number of active layers, which will allow the variation of the non-determinism of the model at each moment of time. We give the notion of the non-determinacy measure and prove that it has the properties of a probability measure. We formulate the problem of reachability with partially specified parameters, layer priorities, and the non-determinacy measure. An algorithm for solving the attainability problem for a neighborhood model with variable indeterminacy and layer priorities is presented. An example of its solution is shown, which shows that when the priorities are compared and the measure of non-determinism is used, the solution of the problem can be obtained more quickly than by a method that does not use priorities. Full article