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Heterologously expressed genes require adaptation to the host organism to ensure adequate levels of protein synthesis, which is typically approached by replacing codons by the target organism’s preferred codons. In view of frequently encountered suboptimal outcomes we introduce the codon-specific elongation model (COSEM) as an alternative concept. COSEM simulates ribosome dynamics during mRNA translation and informs about protein synthesis rates per mRNA in an organism- and context-dependent way. Protein synthesis rates from COSEM are integrated with further relevant covariates such as translation accuracy into a protein expression score that we use for codon optimization. The scoring algorithm further enables fine-tuning of protein expression including deoptimization and is implemented in the software OCTOPOS. The protein expression score produces competitive predictions on proteomic data from prokaryotic, eukaryotic, and human expression systems. In addition, we optimized and tested heterologous expression of manA and ova genes in Salmonella enterica serovar Typhimurium. Superiority over standard methodology was demonstrated by a threefold increase in protein yield compared to wildtype and commercially optimized sequences.
This paper empirically investigates how organizational hierarchy affects the allocation of credit within a bank. Using an exogenous variation in organizational design, induced by a reorganization plan implemented in roughly 2,000 bank branches in India during 1999-2006, and employing a difference-in-differences research strategy, we find that increased hierarchization of a branch decreases its ability to produce "soft" information on loans, leads to increased standardization of loans and rationing of "soft information" loans. Furthermore, this loss of information brings about a reduction in performance on loans: delinquency rates and returns on similar loans are worse in more hierarchical branches. We also document how hierarchical structures perform better in environments that are characterized by a high degree of corruption, thus highlighting the benefits of hierarchical decision making in restraining rent seeking activities. Finally, we document a channel - managerial interference - through which hierarchy affects loan outcomes.
The complexity resulting from intertwined uncertainties regarding model misspecification and mismeasurement of the state of the economy defines the monetary policy landscape. Using the euro area as laboratory this paper explores the design of robust policy guides aiming to maintain stability in the economy while recognizing this complexity. We document substantial output gap mismeasurement and make use of a new model data base to capture the evolution of model specification. A simple interest rate rule is employed to interpret ECB policy since 1999. An evaluation of alternative policy rules across 11 models of the euro area confirms the fragility of policy analysis optimized for any specific model and shows the merits of model averaging in policy design. Interestingly, a simple difference rule with the same coefficients on inflation and output growth as the one used to interpret ECB policy is quite robust as long as it responds to current outcomes of these variables.
In meditation practices that involve focused attention to a specific object, novice practitioners often experience moments of distraction (i.e., mind wandering). Previous studies have investigated the neural correlates of mind wandering during meditation practice through Electroencephalography (EEG) using linear metrics (e.g., oscillatory power). However, their results are not fully consistent. Since the brain is known to be a chaotic/nonlinear system, it is possible that linear metrics cannot fully capture complex dynamics present in the EEG signal. In this study, we assess whether nonlinear EEG signatures can be used to characterize mind wandering during breath focus meditation in novice practitioners. For that purpose, we adopted an experience sampling paradigm in which 25 participants were iteratively interrupted during meditation practice to report whether they were focusing on the breath or thinking about something else. We compared the complexity of EEG signals during mind wandering and breath focus states using three different algorithms: Higuchi's fractal dimension (HFD), Lempel-Ziv complexity (LZC), and Sample entropy (SampEn). Our results showed that EEG complexity was generally reduced during mind wandering relative to breath focus states. We conclude that EEG complexity metrics are appropriate to disentangle mind wandering from breath focus states in novice meditation practitioners, and therefore, they could be used in future EEG neurofeedback protocols to facilitate meditation practice.
Critical discourse hardly knows a more devastating charge against theories, technologies, or structures than that of being reductive. Yet, expansion and growth cannot fare any better today. This volume suspends anti-reductionist reflexes to focus on the experiences and practices of different kinds of reduction, their generative potentials, ethics, and politics. Can their violences be contained and their benefits transported to other contexts?