Recent years have seen intensive progress in measuring protein translation. However, the contributions of coding sequences to the efficiency of the process remain unclear. Here, we identify a universally conserved profile of translation efficiency along mRNAs computed based on adaptation between coding sequences and the tRNA pool. In this profile, the first approximately 30-50 codons are, on average, translated with a low efficiency. Additionally, in eukaryotes, the last approximately 50 codons show the highest efficiency over the full coding sequence. The profile accurately predicts position-dependent ribosomal density along yeast genes. These data suggest that translation speed and, as a consequence, ribosomal density are encoded by coding sequences and the tRNA pool. We suggest that the slow "ramp" at the beginning of mRNAs serves as a late stage of translation initiation, forming an optimal and robust means to reduce ribosomal traffic jams, thus minimizing the cost of protein expression.
Multiple input changes can cause unwanted switching variations, or glitches, in the output of genetic combinational circuits. These glitches can have drastic effects if the output of the circuit causes irreversible changes within or with other cells such as a cascade of responses, apoptosis, or the release of a pharmaceutical in an off-target tissue. Therefore, avoiding unwanted variation of a circuit’s output can be crucial for the safe operation of a genetic circuit. This paper investigates what causes unwanted switching variations in combinational genetic circuits using hazard analysis and a new dynamic model generator. The analysis is done in previously built and modeled genetic circuits with known glitching behavior. The dynamic models generated not only predict the same steady states as previous models but can also predict the unwanted switching variations that have been observed experimentally. Multiple input changes may cause glitches due to propagation delays within the circuit. Modifying the circuit’s layout to alter these delays may change the likelihood of certain glitches, but it cannot eliminate the possibility that the glitch may occur. In other words, function hazards cannot be eliminated. Instead, they must be avoided by restricting the allowed input changes to the system. Logic hazards, on the other hand, can be avoided using hazard-free logic synthesis. This paper demonstrates this by showing how a circuit designed using a popular genetic design automation tool can be redesigned to eliminate logic hazards.
Intuitive spoken dialogues are a prerequisite for human-robot interaction. In many practical situations, robots must be able to identify and focus on sources of interest in the presence of interfering speakers. Techniques such as spatial filtering and blind source separation are therefore often used, but rely on accurate knowledge of the source location. In practice, sound emitted in enclosed environments is subject to reverberation and noise. Hence, sound source localization must be robust to both diffuse noise due to late reverberation, as well as spurious detections due to early reflections. For improved robustness against reverberation, this paper proposes a novel approach for sound source tracking that constructively exploits the spatial diversity of a microphone array installed in a moving robot. In previous work, we developed speaker localization approaches using expectation-maximization (EM) approaches and using Bayesian approaches. In this paper we propose to combine the EM and Bayesian approach in one framework for improved robustness against reverberation and noise.
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