On Ribosome Load, Codon Bias and Protein Abundance

Different codons encoding the same amino acid are not used equally in protein-coding sequences. In bacteria, there is a bias towards codons with high translation rates. This bias is most pronounced in highly expressed proteins, but a recent study of synthetic GFP-coding sequences did not find a correlation between codon usage and GFP expression, suggesting that such correlation in natural sequences is not a simple property of translational mechanisms. Here, we investigate the effect of evolutionary forces on codon usage. The relation between codon bias and protein abundance is quantitatively analyzed based on the hypothesis that codon bias evolved to ensure the efficient usage of ribosomes, a precious commodity for fast growing cells. An explicit fitness landscape is formulated based on bacterial growth laws to relate protein abundance and ribosomal load. The model leads to a quantitative relation between codon bias and protein abundance, which accounts for a substantial part of the observed bias for E. coli. Moreover, by providing an evolutionary link, the ribosome load model resolves the apparent conflict between the observed relation of protein abundance and codon bias in natural sequences and the lack of such dependence in a synthetic gfp library. Finally, we show that the relation between codon usage and protein abundance can be used to predict protein abundance from genomic sequence data alone without adjustable parameters.

Assessment of total uncertainty in cocaine and benzoylecgonine wastewater load measurements

To check the effectiveness of campaigns preventing drug abuse or indicating local effects of efforts against drug trafficking, it is beneficial to know consumed amounts of substances in a high spatial and temporal resolution. The analysis of drugs of abuse in wastewater (WW) has the potential to provide this information. In this study, the reliability of WW drug consumption estimates is assessed and a novel method presented to calculate the total uncertainty in observed WW cocaine (COC) and benzoylecgonine (BE) loads. Specifically, uncertainties resulting from discharge measurements, chemical analysis and the applied sampling scheme were addressed and three approaches presented. These consist of (i) a generic model-based procedure to investigate the influence of the sampling scheme on the uncertainty of observed or expected drug loads, (ii) a comparative analysis of two analytical methods (high performance liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry), including an extended cross-validation by influent profiling over several days, and (iii) monitoring COC and BE concentrations in WW of the largest Swiss sewage treatment plants. In addition, the COC and BE loads observed in the sewage treatment plant of the city of Berne were used to back-calculate the COC consumption. The estimated mean daily consumed amount was 107 ± 21 g of pure COC, corresponding to 321 g of street-grade COC.

A Kinetostatic Formulation for Load-Flow Visualization in Compliant Mechanisms

Load flow visualization, which is an important step in structural and machine assembly design may aid in the analysis and eventual synthesis of compliant mechanisms. In this paper, we present a kineto-static formulation to visualize load flow in compliant mechanisms. This formulation uses the concept of transferred forces to quantify load flow from input to the output of a compliant mechanism. The magnitude and direction of load flow in the constituent members enables functional decomposition of the compliant mechanism into (i) Constraints (C): members that are constrained to deform in a particular direction and (ii) Transmitters (T): members that transmit load to the output. Furthermore, it is shown that a constraint member and an adjacent transmitter member can be grouped together to constitute a fundamental building block known as an CT set whose load flow behavior is maximally decoupled from the rest of the mechanism. We can thereby explain the deformation behavior of a number of compliant mechanisms from literature by visualizing load flow, and identifying building blocks.

Viral load monitoring of antiretroviral therapy, cohort viral load and HIV transmission in Southern Africa: A mathematical modelling analysis

In low-income settings, treatment failure is often identified using CD4 cell count monitoring. Consequently, patients remain on a failing regimen, resulting in a higher risk of transmission. We investigated the benefit of routine viral load monitoring for reducing HIV transmission.

The causal effect of switching to second-line ART in programmes without access to routine viral load monitoring

We examined the effect of switching to second-line antiretroviral therapy (ART) on mortality in patients who experienced immunological failure in ART programmes without access to routine viral load monitoring in sub-Saharan Africa.