Optimization of Time-Course Experiments for Kinetic Model Discrimination

Systems biology relies heavily on the construction of quantitative models of biochemical networks. These models must have predictive power to help unveiling the underlying molecular mechanisms of cellular physiology, but it is also paramount that they are consistent with the data resulting from key experiments. Often, it is possible to find several models that describe the data equally well, but provide significantly different quantitative predictions regarding particular variables of the network. In those cases, one is faced with a problem of model discrimination, the procedure of rejecting inappropriate models from a set of candidates in order to elect one as the best model to use for prediction

A comprehensive assessment of N-terminal signal peptides prediction methods

Background: Amino-terminal signal peptides (SPs) are short regions that guide the targeting of secretory proteins to the correct subcellular compartments in the cell. They are cleaved off upon the passenger protein reaching its destination. The explosive growth in sequencing technologies has led to the deposition of vast numbers of protein sequences necessitating rapid functional annotation techniques, with subcellular localization being a key feature. Of the myriad software prediction tools developed to automate the task of assigning the SP cleavage site of these new sequences, we review here, the performance and reliability of commonly used SP prediction tools. Results: The available signal peptide data has been manually curated and organized into three datasets representing eukaryotes, Gram-positive and Gram-negative bacteria. These datasets are used to evaluate thirteen prediction tools that are publicly available. SignalP (both the HMM and ANN versions) maintains consistency and achieves the best overall accuracy in all three benchmarking experiments, ranging from 0.872 to 0.914 although other prediction tools are narrowing the performance gap. Conclusion: The majority of the tools evaluated in this study encounter no difficulty in discriminating between secretory and non-secretory proteins. The challenge clearly remains with pinpointing the correct SP cleavage site. The composite scoring schemes employed by SignalP may help to explain its accuracy. Prediction task is divided into a number of separate steps, thus allowing each score to tackle a particular aspect of the prediction.12 page(s

Compressibility behaviour of remoulded, finegrained soils and correlation with index properties: Reply

Cherubini et al. have discussed in great detail the merits and demerits of various statistical procedures which can be used to analyze the experimental data and may help to relatively place the various correlation of compression index with the various index properties available in the geotechnical literature. The Authors do agree that the statistical method used by them need not be the best one, but they made use of it for a relative comparison. However, a qualitative look at the plot between compression index Cc and the index property to which it is correlated itself can show which index property is better

Plastic limit and compaction characteristics of fine-grained soils

Laboratory determination of the compaction characteristics of soils is important for use in earthwork constructions. The purpose of compacting earth fills such as earth dams and embankments (highway, railway and canal) is to produce a soil mass that will satisfy the two basic criteria: reduction in settlement and increase in shear strength. For preliminary design and assessment, correlations with the liquid limit have been attempted by various investigators. However, from the present study it is seen that the correlations are not up to a satisfactory level. In this paper the results of detailed investigations carried out are examined to find which of the index properties correlate well with the compaction characteristics. In the analysis, apart from the authors' experimental results, results from the available literature have also been considered. It is found that the plastic limit bears a good correlation with the compaction characteristics, namely optimum moisture content and maximum dry unit weight, much better than liquid limit or plasticity index

Hydraulic conductivity of remolded fine-grained soils versus index properties

Hydraulic conductivity is a dominant parameter in the design of engineered waste disposal facilities such as landfill liners and covers, lagoon liners and slurry walls. It is of interest to a geotechnical or geo-environmental engineer to develop a predictive method of determining the hydraulic conductivity of fine-grained soils, in order to assess its suitability as a liner material. To predict the hydraulic conductivity of soils, researchers and geotechnical engineers have attempted to correlate it with index properties of the soils, such as the liquid limit, void ratio and specific surface. Based on the present study a predictive method has been developed in this paper to predict the hydraulic conductivity in terms of void ratio and shrinkage index (Liquid limit – shrinkage limit) for remoulded fine-grained soils. Though the initial conditions for the soil will affect the hydraulic conductivity behaviour to some extent, both the void ratio and soil characteristics are primary factors in affecting the hydraulic conductivity. Therefore for predictive purpose, the study of hydraulic conductivity behaviour of remoulded fine-grained soils as presented in this paper can be found to be useful for compacted soils also

Compressibility behaviour of remoulded, fine-grained soils and correlation with index properties

Correlating engineering properties with index properties has assumed greater significance in the recent past in the field of geotechnical engineering. Although attempts have been made in the past to correlate compressibility with various index properties individually, all the properties affecting compressibility behaviour have not been considered together in any single study to examine which index property of the soil correlates best with compressibility behaviour, especially within a set of test results. In the present study, 10 soils covering a sufficiently wide range of liquid limit, plastic limit, and shrinkage limit were selected and conventional consolidation tests were carried out starting with their initial water contents almost equal to their respective liquid limits. The compressibility behaviour is vastly different for pairs of soils having nearly the same liquid limit, but different plasticity characteristics. The relationship between void ratio and consolidation pressure is more closely related to the shrinkage index (shrinkage index = liquid limit - shrinkage limit) than to the plasticity index. Wide variations are seen with the liquid limit. For the soils investigated, the compression index relates better with the shrinkage index than with the plasticity index or liquid limit

Effect of pore medium chemistry on hydraulic conductivity of fine grained soils

Hydraulic conductivity of fine-grained soils has assumed greater importance in waste disposal facilities. It is necessary to understand better the factors controlling hydraulic conductivity of fine-grained soils which are used as liners in waste disposal facilities. Hydraulic Conductivity study with ten soils with two fluids having extreme dielectric constants(epsilon) namely water and CCl4 has shown that intrinsic permeability (K) increases drastically with decrease in epsilon. These changes are attributed to the significant reduction in the thickness of diffuse double layer which in turn mainly dependent on the epsilon of the permeant. Hydraulic Conductivity with water of each pair of soils having nearly same liquid limit but different plasticity properties is found to be vastly different, but found to correlate well with shrinkage index, defined as difference between the liquid and the shrinkage limits. Also the ratio Kccl(4)/K-w is found to significantly increase with the increase in the shrinkage index

Absorption water content and liquid limit of soils

Consistency limits are extensively used in geotechnical engineering practice. Besides the consistency limits, the plasticity index, liquidity index, and consistency index have been used to correlate with engineering properties. The test procedures that have been developed to determine liquid limit are based on the strength criterion, and the liquid limit corresponds to a shearing resistance of 1.7 to 2.0 kPa. However, the mechanisms controlling the test procedures do not simulate the mechanisms controlling the water-holding capacity of soils that the liquid limit is supposed to represent. In this paper an attempt has been made to devise a test procedure, known as the absorption test, which simulates the mechanisms controlling the water holding-capacity of soils. The equilibrium water content reached by the dry soil pats starting at shrinkage limit void ratio is found to have a good correlation with the conventional liquid limit obtained from the cone penetrometer method

Coefficient of Consolidation and its Correlation with Index Properties of Remolded Soils

Knowledge of the rate at which the compression of the soil layer takes place is essential from design considerations. This can be achieved by determining the value of the coefficient of consolidation, cv. To obtain cv, it is essential to conduct a routine one-dimensional consolidation test. With the obtained time-compression data, and using any one of the several available curve-fitting procedures, cv can be evaluated. This is a time-consuming process. Also, the fact that many curve-fitting procedures are available in the literature suggests that none of them are completely satisfactory in evaluating cv and, hence, the large variation in the evaluated values by different procedures. Hence, it is desirable to predict the value of cv by any correlation equation relating with some simple index property. This will be quite satisfactory, especially so for preliminary assessment purposes. From the present experimental study on remolded soils, it is found that cv has a better correlation with the shrinkage index, which is the difference between liquid limit and shrinkage limit

Discussion on "Factors influencing undrained strength of fine-grained soils at high water contents"

Following the standard testing procedures, many well-cited publications report variations in undrained strength at the liquid limit obtained by both percussion cup and fall-cone tests. Assuming fixed strength of undrained strength at liquid limit and plastic limit was a matter of convenience. Based on the carefully conducted experiments, it can be observed that the undrained strength at high water contents is not only a function of water content as indicated by the liquid limit, but also significantly influenced by the clay mineral present in the soil. Therefore, soil type as indicated by the soil plasticity, and hence, presence of dominant clay mineral type in the soil has a significant influence on the undrained strength of soils at the liquid limit