Unwanted Evolution Research Articles

Scalable and robust quantum computing on qubit arrays with fixed coupling

We propose a scheme for scalable and robust quantum computing on two-dimensional arrays of qubits with fixed longitudinal coupling. This opens the possibility for bypassing the device complexity associated with tunable couplers required in conventional quantum computing hardware. Our approach is based on driving a subarray of qubits such that the total multi-qubit Hamiltonian can be decomposed into a sum of commuting few-qubit blocks, and efficient optimisation of the unitary evolution within each block. The driving pulses are optimised to implement a target gate on the driven qubits, and at the same time identity gates on the neighbouring undriven qubits, cancelling any unwanted evolution due to the constant qubit-qubit interaction. We show that it is possible to realise a universal set of quantum gates with high fidelity on the basis blocks, and by shifting the driving pattern one can realise an arbitrary quantum circuit on the array. Allowing for imperfect Hamiltonian characterisation, we use robust optimal control to obtain fidelities around 99.99% despite 1% uncertainty in the qubit-qubit and drive-qubit couplings, and a detuning uncertainty at 0.1% of the qubit-qubit coupling strength. This robust feature is crucial for scaling up as parameter uncertainty is significant in large devices.

Which 'imperfect vaccines' encourage the evolution of higher virulence?

Background and objectivesTheory suggests that some types of vaccines against infectious pathogens may lead to the evolution of variants that cause increased harm, particularly when they infect unvaccinated individuals. This theory was supported by the observation that the use of an imperfect vaccine to control Marek’s disease virus in chickens resulted in the virus evolving to be more lethal to unvaccinated birds. This raises the concern that the use of some other vaccines may lead to similar pernicious outcomes. We examine that theory with a focus on considering the regimes in which such outcomes are expected.MethodologyWe evaluate the plausibility of assumptions in the original theory. The previous theory rested heavily on a particular form of transmission–mortality–recovery trade-off and invoked other assumptions about the pathways of evolution. We review alternatives to mortality in limiting transmission and consider evolutionary pathways that were omitted in the original theory.ResultsThe regime where the pernicious evolutionary outcome occurs is narrowed by our analysis but remains possible in various scenarios. We propose a more nuanced consideration of alternative models for the within-host dynamics of infections and for factors that limit virulence. Our analysis suggests imperfect vaccines against many pathogens will not lead to the evolution of pathogens with increased virulence in unvaccinated individuals.Conclusions and implicationsEvolution of greater pathogen mortality driven by vaccination remains difficult to predict, but the scope for such outcomes appears limited. Incorporation of mechanistic details into the framework, especially regarding immunity, may be requisite for prediction accuracy.Lay SummaryA virus of chickens appears to have evolved high mortality in response to a vaccine that merely prevented disease symptoms. Theory has predicted this type of evolution in response to a variety of vaccines and other interventions such as drug treatment. Under what circumstances is this pernicious result likely to occur? Analysis of the theory in light of recent changes in our understanding of viral biology raises doubts that medicine-driven, pernicious evolution is likely to be common. But we are far from a mechanistic understanding of the interaction between pathogen and host that can predict when vaccines and other medical interventions will lead to the unwanted evolution of more virulent pathogens. So, while the regime where a pernicious result obtains may be limited, caution remains warranted in designing many types of interventions.

Verification of a resetting protocol for an uncontrolled superconducting qubit

Quantum resetting protocols allow a quantum system to be sent to a state in the past by making it interact with quantum probes when neither the free evolution of the system nor the interaction is controlled. We experimentally verify the simplest non-trivial case of a quantum resetting protocol, known as the {{mathcal{W}}}_{4} protocol, with five superconducting qubits, testing it with different types of free evolutions and target–probe interactions. After projection, we obtained a reset state fidelity as high as 0.951, and the process fidelity was found to be 0.792. We also implemented 100 randomly chosen interactions and demonstrated an average success probability of 0.323 for left|1rightrangle and 0.292 for left|-rightrangle, and experimentally confirmed the nonzero probability of success for unknown interactions; the numerical simulated values are about 0.3. Our experiment shows that the simplest quantum resetting protocol can be implemented with current technologies, making such protocols a valuable tool in the eternal fight against unwanted evolution in quantum systems.

Suppressing evolution in genetically engineered systems through repeated supplementation.

abstract Genetically engineered organisms are prone to evolve in response to the engineering. This evolution is often undesirable and can negatively affect the purpose of the engineering. Methods that maintain the stability of engineered genomes are therefore critical to the successful design and use of genetically engineered organisms. One potential method to limit unwanted evolution is by taking advantage of the ability of gene flow to counter local adaption, a process of supplementation. Here, we investigate the feasibility of supplementation as a mechanism to offset the evolutionary degradation of a transgene in three model systems: a bioreactor, a gene drive, and a transmissible vaccine. In each model, continual introduction from a stock is used to balance mutation and selection against the transgene. Each system has its unique features. The bioreactor system is especially tractable and has a simple answer: The level of supplementation required to maintain the transgene at a frequency p^ is approximately p^s, where s is the selective disadvantage of the transgene. Supplementation is also feasible in the transmissible vaccine case but is probably not practical to prevent the evolution of resistance against a gene drive. We note, however, that the continual replacement of even a small fraction of a large population can be challenging, limiting the usefulness of supplementation as a means of controlling unwanted evolution.

Directed evolution of Escherichia coli with lower-than-natural plasmid mutation rates.

Unwanted evolution of designed DNA sequences limits metabolic and genome engineering efforts. Engineered functions that are burdensome to host cells and slow their replication are rapidly inactivated by mutations, and unplanned mutations with unpredictable effects often accumulate alongside designed changes in large-scale genome editing projects. We developed a directed evolution strategy, Periodic Reselection for Evolutionarily Reliable Variants (PResERV), to discover mutations that prolong the function of a burdensome DNA sequence in an engineered organism. Here, we used PResERV to isolate Escherichia coli cells that replicate ColE1-type plasmids with higher fidelity. We found mutations in DNA polymerase I and in RNase E that reduce plasmid mutation rates by 6- to 30-fold. The PResERV method implicitly selects to maintain the growth rate of host cells, and high plasmid copy numbers and gene expression levels are maintained in some of the evolved E. coli strains, indicating that it is possible to improve the genetic stability of cellular chassis without encountering trade-offs in other desirable performance characteristics. Utilizing these new antimutator E. coli and applying PResERV to other organisms in the future promises to prevent evolutionary failures and unpredictability to provide a more stable genetic foundation for synthetic biology.

Towards Improved Li-O2 Batteries: Understanding the Role of Dissolved Redox Mediators

Aprotic lithium-oxygen (Li-O2) batteries emerged as promising energy stores as they exhibit an exceptionally high theoretical energy density. However, their practical application is still hindered by high charging overvoltages arising from the electronically insulating nature of the insoluble reaction product lithium peroxide (Li2O2). Recently, dissolved redox mediators (RMs) like tertrathiafulvalene (TTF), lithium iodide (LiI) and 2,2,6,6-tetramethylpiperidinyloxyl (TEMPO) have been introduced as an efficient tool to reduce the charging overvoltages and increase the lifetime [1,2,3]. Herein, we present a systematic study on the underlying principles of redox mediators in Li-O2 batteries and introduce an advanced cell system providing improved capacity and cycling stability. At first, the impact of the different cell parameters on the charging profile of Li-O2 batteries with redox mediators is elucidated and an appropriate model is derived. The model is validated by potentiostatic measurements using a modified cell setup which enables the precise control of the different cell parameters. According to the model, the electrochemical properties of the redox mediator and the morphology of the reaction products are identified as the major impact factors. Subsequently, the model is applied to different cyclic nitroxides, which show a direct relation between structure and performance as redox mediator in Li-O2 batteries. Herein, the nitroxide 1-Methyl-2-azaadamantane N-oxyl emerged as the most efficient redox mediator, as it enables charging of Li-O2 batteries completely below 3.6 V vs. Li+/Li [4]. The concept of redox mediators in aprotic Li-O2 batteries has been further advanced by incorporating a solid Li+ conducting membrane between cathode and anode. This hybrid setup improves the cycling stability and increases the discharge capacity. The Li+ conducting membrane prevents the deactivation of RM+ at the anode and the unwanted shuttling of the redox mediator between both electrodes. It is demonstrated by means of UV-Vis spectroscopy, XRD and pressure monitoring that the redox mediator oxidation and reduction reactions (RMOR and RMRR) are included into the charge cycling of hybrid Li-O2 batteries. Depending on the concentration of the mediator, the capacity is raised by up to 500 mAh/gC in this study. Unexpectedly, the implementation of the Li+ selective membrane additionally improves the cycling stability, as the unwanted evolution of CO2 is distinctly reduced. These results indicate that the lithium anode contributes to the cathodic decomposition reaction in regular Li-O2 batteries without a membrane. In summary, this work provides a comprehensive understanding of the reactions in Li-O2 batteries with dissolved redox mediators and introduces a sustainable concept for their further development. [1] Chen et al., Nat. Chem. 2013, 5, 489. [2] Lim et al., Angew. Chem. Int. Ed. 2014, 53, 4007. [3] Bergner et al., J. Am. Chem. Soc. 2014, 136, 15054. [4] Bergner et al., Phys. Chem. Chem. Phys. 2015, 17, 31769.

Predicting the Genetic Stability of Engineered DNA Sequences with the EFM Calculator.

Unwanted evolution can rapidly degrade the performance of genetically engineered circuits and metabolic pathways installed in living organisms. We created the Evolutionary Failure Mode (EFM) Calculator to computationally detect common sources of genetic instability in an input DNA sequence. It predicts two types of mutational hotspots: deletions mediated by homologous recombination and indels caused by replication slippage on simple sequence repeats. We tested the performance of our algorithm on genetic circuits that were previously redesigned for greater evolutionary reliability and analyzed the stability of sequences in the iGEM Registry of Standard Biological Parts. More than half of the parts in the Registry are predicted to experience >100-fold elevated mutation rates due to the inclusion of unstable sequence configurations. We anticipate that the EFM Calculator will be a useful negative design tool for avoiding volatile DNA encodings, thereby increasing the evolutionary lifetimes of synthetic biology devices.

Evolutionary applications research highlight for issue 1.

As we highlight each month in this section, the application of evolutionary theory to issues affecting the health and well-being of human, agricultural, and natural populations is gaining increasing momentum. In a recent review article written for Science, Scott Carroll et al. take on the now monumental task of synthesizing the many ways that evolutionary biology can be used to address global challenges (Carroll et al. 2014). They comprehensively explore the main problems being tackled with an evolutionary approach, ranging from populations evolving too quickly (such as emerging pathogens or pests evolving resistance to treatment) to populations not evolving quickly enough (for example those being negatively affected by human-mediated change). The authors begin by identifying what they see as the two key paradigms of applied evolutionary biology: (i) managing contemporary evolution (i.e., manipulating the rapid evolutionary response of short-lived organisms with large population sizes, such as bacterial pathogens) and (ii) altering the phenotype–environment mismatch (i.e., responding to populations of long-lived organisms such as trees that are no longer well adapted to their local environment due to shifts in climatic conditions or changes in biotic interactions). As a great example of such a mismatch, the authors highlight the increasing rates of obesity, diabetes, and heart disease in the human populations as a result of a more sedentary lifestyle with diets rich in sugars and fat. They then identify a number of promising research avenues that either have addressed or have the potential to address current global challenges, covering a wide range of approaches including the use of genetic engineering to more appropriately match genomes to their environment, the use of ‘refuges’ in agriculture and combination treatments against pests and pathogens to hinder the evolution of resistance, and introducing nonlocal genotypes which are predicted to perform better under given environmental conditions into natural populations to increase local adaptation. The article nicely separates these conceptual approaches into strategies for slowing unwanted evolution or directly influencing fitness of pests and pathogens, strategies for reducing the mismatch between phenotype and the local environment, and strategies for increasing group performance by selecting on group-level traits. For example, the authors discuss the success of artificially selecting for group yield in agricultural plots rather than individual fitness as a means for decreasing competition among plants. Critically, the piece also emphasizes the need to take a unified approach in meeting international objectives for sustainable development and suggests a need for stricter enforcement of guidelines in order to ensure best practice is achieved despite temptation to put profit or immediate success ahead of sustainable solutions. Overall, the review acts as a unique and remarkable resource both for researchers and students who are new to the field of applied evolution and those who actively contribute to the field.

Applying evolutionary biology to address global challenges.

Two categories of evolutionary challenges result from escalating human impacts on the planet. The first arises from cancers, pathogens, and pests that evolve too quickly and the second, from the inability of many valued species to adapt quickly enough. Applied evolutionary biology provides a suite of strategies to address these global challenges that threaten human health, food security, and biodiversity. This Review highlights both progress and gaps in genetic, developmental, and environmental manipulations across the life sciences that either target the rate and direction of evolution or reduce the mismatch between organisms and human-altered environments. Increased development and application of these underused tools will be vital in meeting current and future targets for sustainable development.

English

To remain useful for their users, software systems need to continuously enhance and extend their functionality. Nevertheless, in many object-oriented applications, features are not represented explicitly. The lack of modularization is known to make application features difficult to locate, to comprehend and to modify in isolation from one another. In our work, we implement restructuring using Featureous plug-in where we can change the classes between packages. In the previous literature works, lot of complexities arises while using the tool due to dependencies. Changes to the code without knowing the root cause of the problem leads to further production of new errors. So, we aim in finding the restructuring candidates which have to be rearranged, thereby applying changes to the code on those parts using the tool helps in ordered arrangement of the source code. Applying modularization to the restructuring candidates will lead to decrease in the human effort as well as tool effort in restructuring. Unwanted evolution of new errors will be eliminated

Rupture post-traumatique négligée du retinaculum extensorum à la cheville. À propos d’un cas et revue de la littérature

Post-traumatic ruptures of the retinaculum extensorum (RE) to the ankle is rare and behind a tendinous luxation, of a rope effect, tiredness and weakening or loss of strength. We report the observation of a patient aged 35 practicing full contact for 20 years, victim of a sports accident two years before upon a foot kick in the kicking bag during a training session bringing about a rupture of the RE at the ankle. Imagery (echography and MRI) made sure the clinical exam and to call for the diagnosis of the rupture of the lower band of the retinaculum with subluxation of the tendons of the tibialis anterior and of the extensor hellucis longus. The take in charge consisted of a local plasty of the RE. On the relapse (6months), the patient is satisfied with the outcome and taking back to his initial sports activity. Through our observation and a review of the literature, we attempt to review the anatomy of the RE to the ankle and to analyze the causes and the consequences of its rupture as well as the usefulness of the imagery in analyzing its anatomic structure. The rupture of the RE is a rare affection mainly affecting sports persons. They can be unseen and may compromise the sports career of athletes. A meticulous clinical exam and targeting imagery as well as an adequate take in charge allow avoiding this unwanted evolution.

Demonstration of Sufficient Control for Two Rounds of Quantum Error Correction in a Solid State Ensemble Quantum Information Processor

We report the implementation of a 3-qubit quantum error-correction code on a quantum information processor realized by the magnetic resonance of carbon nuclei in a single crystal of malonic acid. The code corrects for phase errors induced on the qubits due to imperfect decoupling of the magnetic environment represented by nearby spins, as well as unwanted evolution under the internal Hamiltonian. We also experimentally demonstrate sufficiently high-fidelity control to implement two rounds of quantum error correction. This is a demonstration of state-of-the-art control in solid state nuclear magnetic resonance, a leading test bed for the implementation of quantum algorithms.

Design of strongly modulating pulses to implement precise effective Hamiltonians for quantum information processing

We describe a method for improving coherent control through the use of detailed knowledge of the system’s Hamiltonian. Precise unitary transformations were obtained by strongly modulating the system’s dynamics to average out unwanted evolution. With the aid of numerical search methods, pulsed irradiation schemes are obtained that perform accurate, arbitrary, selective gates on multiqubit systems. Compared to low power selective pulses, which cannot average out all unwanted evolution, these pulses are substantially shorter in time, thereby reducing the effects of relaxation. Liquid-state nuclear magnetic resonance techniques on homonuclear spin systems are used to demonstrate the accuracy of these gates both in simulation and experiment. Simulations of the coherent evolution of a three-qubit system show that the control sequences faithfully implement the unitary operations, typically yielding gate fidelities on the order of 0.999 and, for some sequences, up to 0.9997. The experimentally determined density matrices resulting from the application of different control sequences on a three-spin system have overlaps of up to 0.99 with the expected states, confirming the quality of the experimental implementation.