The case-only odds ratio as a causal parameter

In the simplest case-only design, cases of a disease are cross-classified into a 2 x 2 table describing a genotype attribute and exposure to some environmental agent. In some instances, the genetic attribute has described inherited genes; in other instances, it has described mutations, for instance, damage to proto-oncogenes or tumor suppressor genes leading to cancer. Here, the population case-only odds ratio is written as a causal parameter in terms of potential outcomes with and without exposure to the agent. It is shown that the case-only odds ratio makes sense as a causal parameter with inherited genes, but its magnitude does not have a causal interpretation with mutations, although deviations from 1 do provide information. The difference is that the environmental agent certainly did not cause an individual to inherit particular genes, but it may have caused the mutation.     

The fluorescence intensities ratio is not a reliable parameter for evaluation of protein unfolding transitions

Monitoring the fluorescence of proteins, particularly the fluorescence of intrinsic tryptophan residues, is a popular method often used in the analysis of unfolding transitions (induced by temperature, chemical denaturant, and pH) in proteins. The tryptophan fluorescence provides several suitable parameters, such as steady‐state fluorescence intensity, apparent quantum yield, mean fluorescence lifetime, position of emission maximum that are often utilized for the observation of the conformational/unfolding transitions of proteins. In addition, the fluorescence intensities ratio at different wavelengths (usually at 330 nm and 350 nm) is becoming an increasingly popular parameter for the evaluation of thermal transitions. We show that, under certain conditions, the use of this parameter for the analysis of unfolding transitions leads to the incorrect determination of thermodynamic parameters characterizing unfolding transitions in proteins (e.g., melting temperature) and, hence, can compromise the hit identification during high‐throughput drug screening campaigns.     

The Malthusian parameter and the effective rate of increase

This paper reviews and contrasts two classses of population models, three measures of growth rate and three measures of population size. We analyse the conditions under which the new measures of growth rate reduce to the Malthusian parameter and also the conditions under which the new measures of population size reduce to the census size.     

The AgNOR quantity as prognostic parameter in choroidal melanomas: a standardised analysis.

In order to assess the prognostic significance of silver-stained nucleolar organizer region (AgNOR) proteins, a standardised analysis has been performed on 34 ocular globes with choroidal melanomas. On formalin-fixed paraffin-embedded sections, the visualisation and quantification of AgNORs were achieved according to the guidelines of the Committee on AgNOR Quantification (1995); statistical analysis was performed on the mean AgNOR area values (NORA). We have encountered significantly higher NORA values in nonspindle shaped elements, in tumours of larger dimensions as well as in those with worse clinical course; no correlations were achieved when the AgNOR quantity was compared with age, sex and amount of pigment. The comparison of Kaplan-Meier survival curves revealed that patients affected by melanomas with higher NORA values (>3.327 microm2), non-spindle cell histotype and increased size of tumour had a worse prognosis; finally, by Cox multivariate analysis, the AgNOR quantity appeared the only independent prognostic variable to predict the final outcome of patients.     

OBIYagns: a grid-based biochemical simulator with a parameter estimator

SUMMARY: OBIYagns (yet another gene network simulator) is a biochemical system simulator that comprises a multiple-user Web-based graphical interface, an ordinary differential equation solver and a parameter estimators distributed over an open bioinformatics grid (OBIGrid). This grid-based biochemical simulation system can achieve high performance and provide a secure simulation environment for estimating kinetic parameters in an acceptable time period. OBIYagns can be applied to larger system biology-oriented simulation projects. AVAILABILITY: OBIYagns example models, methods and user guide are available at https://access.obigrid.org/yagns/ SUPPLEMENTARY INFORMATION: Please refer to Bioinformatics online.     

Complex parameter landscape for a complex neuron model

The electrical activity of a neuron is strongly dependent on the ionic channels present in its membrane. Modifying the maximal conductances from these channels can have a dramatic impact on neuron behavior. But the effect of such modifications can also be cancelled out by compensatory mechanisms among different channels. We used an evolution strategy with a fitness function based on phase-plane analysis to obtain 20 very different computational models of the cerebellar Purkinje cell. All these models produced very similar outputs to current injections, including tiny details of the complex firing pattern. These models were not completely isolated in the parameter space, but neither did they belong to a large continuum of good models that would exist if weak compensations between channels were sufficient. The parameter landscape of good models can best be described as a set of loosely connected hyperplanes. Our method is efficient in finding good models in this complex landscape. Unraveling the landscape is an important step towards the understanding of functional homeostasis of neurons.