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We consider a quantum Otto cycle with a q-deformed quantum oscillator working substance and classical thermal baths. We investigate the influence of the quantum statistical deformation parameter q on the work and efficiency of the cycle. In usual quantum Otto cycle, a Hamiltonian parameter is varied during the quantum adiabatic stages while the quantum statistical character of the working substance remains fixed. We point out that even if the Hamiltonian parameters are not changing, work can be harvested by quantum statistical changes of the working substance. Work extraction from thermal resources using quantum statistical mutations of the working substance makes a quantum Otto cycle without any classical analog.
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BACKGROUND: Locally advanced breast cancer (LABC) rates are unusually high in developing countries. There is a need for the identification of predictive biomarkers for the selection of patients who could benefit from neoadjuvant chemotherapy (NAC). AIM: As the expression of ALU repeat is increased in cancer and has not been assessed in liquid biopsy of cancer patients, our goal was to assess ALU expression in the blood plasma of LABC patients during NAC. PATIENTS AND METHODS: Plasma samples drawn at baseline and at the end of the fourth cycle of chemotherapy were used to determine the plasma levels of ALU-RNA by quantitative real-time PCR. RESULTS: ALU expression from baseline to the fourth cycle of NAC increased from a median relative level of 1870 to 3370 in the whole group (p = 0.03). The increase in ALU-RNA levels in the course of NAC was more pronounced in premenopausal women and in patients with hormone-positive tumors. In patients with complete response to NAC, baseline ALU expression was higher than that in those with partial response. CONCLUSION: This exploratory study provides evidence that plasma ALU-RNA levels are modulated by the menopausal status and hormone receptor status of breast cancer patients and pre-therapeutic ALU-RNA levels might be useful in predicting the response to chemotherapy in a neoadjuvant setting.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Terapia Neoadjuvante , RNA/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
Enantiomers are chiral molecules that exist in right-handed and left-handed conformations. Optical techniques of enantiomers' detection are widely employed to discriminate between left- and right-handed molecules. However, identical spectra of enantiomers make enantiomer detection a very challenging task. Here, we investigate the possibility of exploiting thermodynamic processes for enantiomer detection. In particular, we employ a quantum Otto cycle in which a chiral molecule described by a three-level system with cyclic optical transitions is considered a working medium. Each energy transition of the three-level system is coupled with an external laser drive. We find that the left- and right-handed enantiomers operate as a quantum heat engine and a thermal accelerator, respectively, when the overall phase is the control parameter. In addition, both enantiomers act as heat engines by keeping the overall phase constant and using the laser drives' detuning as the control parameter during the cycle. However, the molecules can still be distinguished because both cases' extracted work and efficiency are quantitatively very different. Accordingly, the left- and right-handed molecules can be distinguished by evaluating the work distribution in the Otto cycle.
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Neural mass models (NMMs) are important for helping us interpret observations of brain dynamics. They provide a means to understand data in terms of mechanisms such as synaptic interactions between excitatory and inhibitory neuronal populations. To interpret data using NMMs we need to quantitatively compare the output of NMMs with data, and thereby find parameter values for which the model can produce the observed dynamics. Mapping dynamics to NMM parameter values in this way has the potential to improve our understanding of the brain in health and disease. Though abstract, NMMs still comprise of many parameters that are difficult to constrain a priori. This makes it challenging to explore the dynamics of NMMs and elucidate regions of parameter space in which their dynamics best approximate data. Existing approaches to overcome this challenge use a combination of linearising models, constraining the values they can take and exploring restricted subspaces by fixing the values of many parameters a priori. As such, we have little knowledge of the extent to which different regions of parameter space of NMMs can yield dynamics that approximate data, how nonlinearities in models can affect parameter mapping or how best to quantify similarities between model output and data. These issues need to be addressed in order to fully understand the potential and limitations of NMMs, and to aid the development of new models of brain dynamics in the future. To begin to overcome these issues, we present a global nonlinear approach to recovering parameters of NMMs from data. We use global optimisation to explore all parameters of nonlinear NMMs simultaneously, in a minimally constrained way. We do this using multi-objective optimisation (multi-objective evolutionary algorithm, MOEA) so that multiple data features can be quantified. In particular, we use the weighted horizontal visibility graph (wHVG), which is a flexible framework for quantifying different aspects of time series, by converting them into networks. We study EEG alpha activity recorded during the eyes closed resting state from 20 healthy individuals and demonstrate that the MOEA performs favourably compared to single objective approaches. The addition of the wHVG objective allows us to better constrain the model output, which leads to the recovered parameter values being restricted to smaller regions of parameter space, thus improving the practical identifiability of the model. We then use the MOEA to study differences in the alpha rhythm observed in EEG recorded from 20 people with epilepsy. We find that a small number of parameters can explain this difference and that, counterintuitively, the mean excitatory synaptic gain parameter is reduced in people with epilepsy compared to control. In addition, we propose that the MOEA could be used to mine for the presence of pathological rhythms, and demonstrate the application of this to epileptiform spike-wave discharges.
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Epilepsia , Modelos Neurológicos , Humanos , Simulação por Computador , Neurônios/fisiologia , Encéfalo/fisiologia , Dinâmica não LinearRESUMO
BackgroundAssessing circadian rhythmicity from infrequently sampled data is challenging; however, these types of data are often encountered when measuring circadian transcripts in hospitalized patients.MethodsWe present ClinCirc. This method combines 2 existing mathematical methods (Lomb-Scargle periodogram and cosinor) sequentially and is designed to measure circadian oscillations from infrequently sampled clinical data. The accuracy of this method was compared against 9 other methods using simulated and frequently sampled biological data. ClinCirc was then evaluated in 13 intensive care unit (ICU) patients as well as in a separate cohort of 29 kidney-transplant recipients. Finally, the consequences of circadian alterations were investigated in a retrospective cohort of 726 kidney-transplant recipients.ResultsClinCirc had comparable performance to existing methods for analyzing simulated data or clock transcript expression of healthy volunteers. It had improved accuracy compared with the cosinor method in evaluating circadian parameters in PER2:luc cell lines. In ICU patients, it was the only method investigated to suggest that loss of circadian oscillations in the peripheral oscillator was associated with inflammation, a feature widely reported in animal models. Additionally, ClinCirc was able to detect other circadian alterations, including a phase shift following kidney transplantation that was associated with the administration of glucocorticoids. This phase shift could explain why a significant complication of kidney transplantation (delayed graft dysfunction) oscillates according to the time of day kidney transplantation is performed.ConclusionClinCirc analysis of the peripheral oscillator reveals important clinical associations in hospitalized patients.FundingUK Research and Innovation (UKRI), National Institute of Health Research (NIHR), Engineering and Physical Sciences Research Council (EPSRC), National Institute on Academic Anaesthesia (NIAA), Asthma+Lung UK, Kidneys for Life.
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Algoritmos , Ritmo Circadiano , Transplante de Rim , Linhagem Celular , Ritmo Circadiano/fisiologia , Glucocorticoides/farmacologia , Glucocorticoides/uso terapêutico , Estudos Retrospectivos , Humanos , Transplante de Rim/efeitos adversos , Unidades de Terapia IntensivaRESUMO
Boolean Delay Equations (BDEs) can simulate surprisingly complex behavior, despite their relative simplicity. In addition to steady-state dynamics, BDEs can also generate periodic and quasiperiodic oscillations, m:n frequency locking, and even chaos. Further, the enumerability of Boolean update functions and their compact parametrization means that BDEs can be leveraged to generate low-level descriptions of biological networks, from which more detailed formulations (e.g., differential equation models) can be constructed. However, although several studies have demonstrated the utility of BDE modeling in computational biology, a current barrier to the wider adoption of the BDE approach is the absence of freely available simulation software. In this work, we present BDEtools-an open-source MATLAB package for numerically solving BDE models. After giving a brief introduction to BDE modeling, we describe the package's solver algorithms, together with several utility functions that can be used to provide solver inputs and to process solver outputs. We also demonstrate the functionality of BDEtools by illustrating its application to an established model of a gene regulatory network that controls circadian rhythms. BDEtools makes it straightforward for researchers to quickly build reliable BDE models of biological networks. We hope that its ease of use and free availability will encourage more researchers to explore BDE formulations of their systems of interest. Through the continued use of BDEs by the computational biology community, we will, no doubt, discover their potential applicability to a broader class of biological networks.
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Modelos Biológicos , Software , Simulação por Computador , Algoritmos , Redes Reguladoras de GenesRESUMO
Recent experiments at the nanoscales confirm that thermal rectifiers, the thermal equivalent of electrical diodes, can operate in the quantum regime. We present a thorough investigation of the effect of different particle exchange statistics, coherence, and collective interactions on the quantum heat transport of rectifiers with two-terminal junctions. Using a collision model approach to describe the open system dynamics, we obtain a general expression of the nonlinear heat flow that fundamentally deviates from the Landauer formula whenever quantum statistical or coherence asymmetries are present in the bath particles. Building on this, we show that heat rectification is possible even with symmetric medium-bath couplings if the two baths differ in quantum statistics or coherence. Furthermore, the associated thermal conductance vanishes exponentially at low temperatures as in the Coulomb-blockade effect. However, at high temperatures it acquires a power-law behavior depending on the quantum statistics. Our results can be significant for heat management in hybrid open quantum systems or solid-state thermal circuits.
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We investigate quantum Otto engine and refrigeration cycles of a time-dependent harmonic oscillator operating under the conditions of maximum Ω function, a trade-off objective function which represents a compromise between energy benefits and losses for a specific job, for both adiabatic and nonadiabatic (sudden) frequency modulations. We derive analytical expressions for the efficiency and coefficient of performance of the Otto cycle. For the case of adiabatic driving, we point out that in the low-temperature regime, the harmonic Otto engine (refrigerator) can be mapped to Feynman's ratchet and pawl model which is a steady-state classical heat engine. For the sudden switch of frequencies, we obtain loop-like behavior of the efficiency-work curve, which is characteristic of irreversible heat engines. Finally, we discuss the behavior of cooling power at maximum Ω function.
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The high energy transfer efficiency of photosynthetic complexes has been a topic of research across many disciplines. Several attempts have been made in order to explain this energy transfer enhancement in terms of quantum mechanical resources such as energetic and vibration coherence and constructive effects of environmental noise. The developments in this line of research have inspired various biomimetic works aiming to use the underlying mechanisms in biological light harvesting complexes for the improvement of synthetic systems. In this article, we explore the effect of an auxiliary hierarchically structured environment interacting with a system on the steady-state heat transport across the system. The cold and hot baths are modeled by a series of identically prepared qubits in their respective thermal states, and we use a collision model to simulate the open quantum dynamics of the system. We investigate the effects of system-environment, inter-environment couplings and coherence of the structured environment on the steady state heat flux and find that such a coupling enhances the energy transfer. Our calculations reveal that there exists a non-monotonic and non-trivial relationship between the steady-state heat flux and the mentioned parameters.
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The circadian system-an organism's built-in biological clock-is responsible for orchestrating biological processes to adapt to diurnal and seasonal variations. Perturbations to the circadian system (e.g., pathogen attack, sudden environmental change) often result in pathophysiological responses (e.g., jetlag in humans, stunted growth in plants, etc.) In view of this, synthetic biologists are progressively adapting the idea of employing synthetic feedback control circuits to alleviate the effects of perturbations on circadian systems. To facilitate the design of such controllers, suitable models are required. Here, we extend our recently developed model for the plant circadian clock-termed the extended S-System model-to model circadian systems across different kingdoms of life. We then use this modeling strategy to develop a design framework, based on an antithetic integral feedback (AIF) controller, to restore a gene's circadian profile when it is subject to loss-of-function due to external perturbations. The use of the AIF controller is motivated by its recent successful experimental implementation. Our findings provide circadian biologists with a systematic and general modeling and design approach for implementing synthetic feedback control of circadian systems.
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Fenômenos Biológicos , Relógios Circadianos , Relógios Circadianos/genética , Retroalimentação , Humanos , Modelos BiológicosRESUMO
We investigate heat rectification in a two-qubit system coupled via the Dzyaloshinskii-Moriya (DM) interaction. We derive analytical expressions for heat currents and thermal rectification and provide possible physical mechanisms behind the observed results. We show that the anisotropy of DM interaction in itself is insufficient for heat rectification, and some other form of asymmetry is needed. We employ off-resonant qubits as the source of this asymmetry. We find the regime of parameters for higher rectification factors by examining the analytical expressions of rectification obtained from a global master equation solution. In addition, it is shown that the direction and quality of rectification can be controlled via various system parameters. Furthermore, we compare the influence of different orientations of the DM field anisotropy on the performance of heat rectification. Finally, we investigate the possible interplay between quantum correlations and the performance of the quantum thermal rectifier. We find that asymmetry in the coherences is a fundamental resource for the performance of the quantum thermal rectifier.
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We investigate the implications of quantum Darwinism in a composite quantum system with interacting constituents exhibiting a decoherence-free subspace. We consider a two-qubit system coupled to an N-qubit environment via a dephasing interaction. For excitation preserving interactions between the system qubits, an analytical expression for the dynamics is obtained. It demonstrates that part of the system Hilbert space redundantly proliferates its information to the environment, while the remaining subspace is decoupled and preserves clear non-classical signatures. For measurements performed on the system, we establish that a non-zero quantum discord is shared between the composite system and the environment, thus violating the conditions of strong Darwinism. However, due to the asymmetry of quantum discord, the information shared with the environment is completely classical for measurements performed on the environment. Our results imply a dichotomy between objectivity and classicality that emerges when considering composite systems.
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We propose to use a few-qubit system as a compact quantum refrigerator for cooling an interacting multi-qubit system. We specifically consider a central qubit coupled to N ancilla qubits in a so-called spin-star model to be used as refrigerant by means of short interactions with a many-qubit system to be cooled. We first show that if the interaction between the qubits is of the longitudinal and ferromagnetic Ising model form, the central qubit is colder than the environment. We summarize how preparing the refrigerant qubits using the spin-star model paves the way for the cooling of a many-qubit system by means of a collisional route to thermalization. We discuss a simple refrigeration cycle, considering the operation cost and cooling efficiency, which can be controlled by N and the qubit-qubit interaction strength. Besides, bounds on the achievable temperature are established. Such few-qubit compact quantum refrigerators can be significant to reduce dimensions of quantum technology applications, can be easy to integrate into all-qubit systems, and can increase the speed and power of quantum computing and thermal devices.
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We present a new computational approach to analyse nystagmus waveforms. Our framework is designed to fully characterise the state of the nystagmus, aid clinical diagnosis and to quantify the dynamical changes in the oscillations over time. Both linear and nonlinear analyses of time series were used to determine the regularity and complexity of a specific homogenous phenotype of nystagmus. Two-dimensional binocular eye movement recordings were carried out on 5 adult subjects who exhibited a unilateral, uniplanar, vertical nystagmus secondary to a monocular late-onset severe visual loss in the oscillating eye (the Heimann-Bielschowsky Phenomenon). The non-affected eye held a central gaze in both horizontal and vertical planes (± 10 min. of arc). All affected eyes exhibited vertical oscillations, with mean amplitudes and frequencies ranging from 2.0°-4.0° to 0.25-1.5 Hz, respectively. Unstable periodic orbit analysis revealed only 1 subject exhibited a periodic oscillation. The remaining subjects were found to display quasiperiodic (n = 1) and nonperiodic (n = 3) oscillations. Phase space reconstruction allowed attractor identification and the computation of a time series complexity measure-the permutation entropy. The entropy measure was found to be able to distinguish between a periodic oscillation associated with a limit cycle attractor, a quasiperiodic oscillation associated with a torus attractor and nonperiodic oscillations associated with higher-dimensional attractors. Importantly, the permutation entropy was able to rank the oscillations, thereby providing an objective index of nystagmus complexity (range 0.15-0.21) that could not be obtained via unstable periodic orbit analysis or attractor identification alone. These results suggest that our framework provides a comprehensive methodology for characterising nystagmus, aiding differential diagnosis and also permitting investigation of the waveforms over time, thereby facilitating the quantification of future therapeutic managements. In addition, permutation entropy could provide an additional tool for future oculomotor modelling.
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The rapid eye movements (saccades) used to transfer gaze between targets are examples of an action. The behaviour of saccades matches that of the slow-fast model of actions originally proposed by Zeeman. Here, we extend Zeeman's model by incorporating an accumulator that represents the increase in certainty of the presence of a target, together with an integrator that converts a velocity command to a position command. The saccadic behaviour of several foveate species, including human, rhesus monkey and mouse, is replicated by the augmented model. Predictions of the linear stability of the saccadic system close to equilibrium are made, and it is shown that these could be tested by applying state-space reconstruction techniques to neurophysiological recordings. Moreover, each model equation describes behaviour that can be matched to specific classes of neurons found throughout the oculomotor system, and the implication of the model is that build-up, burst and omnipause neurons are found throughout the oculomotor pathway because they constitute the simplest circuit that can produce the motor commands required to specify the trajectories of motor actions.
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Movimentos Oculares , Movimentos Sacádicos , Animais , Macaca mulatta , Camundongos , NeurôniosRESUMO
OBJECTIVES: In the present study, cellular or exosomal expression of H19, an oncofetal lncRNA gene, was evaluated during androgen stimulation via dihydrotestosterone (DHT) or AR blockage via enzalutamide in cultured hormone-sensitive Pca cells which overexpres AR (LNCaP-AR+). BACKGROUND: Prostate cancer (PCa) is an androgen-dependent disease. Androgen receptor (AR) antagonists (i.e. enzalutamide) have been used for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC). Exosomes and their contents (non-coding RNA) play an important role in tumor development and progression. METHODS: Cells were treated with DHT (10 nM) and/or enzalutamide (10 uM) for 24 h. Cellular and exosomal expression of H19 was investigated using a quantitative polymerase chain reaction assay. RESULTS: Our findings reveal that cellular H19 expression decreased approximately 2.3fold in mean upon androgen stimulation of Pca cells. AR blockage using enzalutamide restored DHT effect and we found increased H19 expression (≤ 2.5-fold, p < 0.05) upon the combined use of DHT and enzalutamide compared to control cells. Similar to its cellular effect, DHT treatment also led to declined exosomal expression of H19 (≤ 3-fold, p < 0.0001). Restorative effect of enzalutamide on decreased H19 expression induced by androgen stimulation was not observed in exosomes. CONCLUSION: This experimental study provides evidence that H19 might be involved in androgen receptor pathway. Further research is needed to explore the role of H19 in Pca and intercellular communication via exosomes (Fig. 2, Ref. 32).
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Exossomos , Neoplasias de Próstata Resistentes à Castração , RNA Longo não Codificante , Linhagem Celular Tumoral , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , RNA Longo não Codificante/metabolismo , Receptores AndrogênicosRESUMO
The circadian clock orchestrates biological processes so that they occur at specific times of the day, thereby facilitating adaptation to diurnal and seasonal environmental changes. In plants, mathematical modelling has been comprehensively integrated with experimental studies to gain a better mechanistic understanding of the complex genetic regulatory network comprising the clock. However, with an increasing number of circadian genes being discovered, there is a pressing need for methods facilitating the expansion of computational models to incorporate these newly-discovered components. Conventionally, plant clock models have comprised differential equation systems based on Michaelis-Menten kinetics. However, the difficulties associated with modifying interactions using this approach-and the concomitant problem of robustly identifying regulation types-has contributed to a complexity bottleneck, with quantitative fits to experimental data rapidly becoming computationally intractable for models possessing more than ≈50 parameters. Here, we address these issues by constructing the first plant clock models based on the S-System formalism originally developed by Savageau for analysing biochemical networks. We show that despite its relative simplicity, this approach yields clock models with comparable accuracy to the conventional Michaelis-Menten formalism. The S-System formulation also confers several key advantages in terms of model construction and expansion. In particular, it simplifies the inclusion of new interactions, whilst also facilitating the modification of regulation types, thereby making it well-suited to network inference. Furthermore, S-System models mitigate the issue of parameter identifiability. Finally, by applying linear systems theory to the models considered, we provide some justification for the increased use of aggregated protein equations in recent plant clock modelling, replacing the separate cytoplasmic/nuclear protein compartments that were characteristic of the earlier models. We conclude that as well as providing a simplified framework for model development, the S-System formalism also possesses significant potential as a robust modelling method for designing synthetic gene circuits.
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Relógios Circadianos , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano , Modelos Biológicos , Fenômenos Fisiológicos Vegetais/genética , Arabidopsis/genética , Arabidopsis/fisiologia , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Relógios Circadianos/genética , Relógios Circadianos/fisiologia , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/genética , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/metabolismo , Biologia Computacional , Redes Reguladoras de Genes/genética , Redes Reguladoras de Genes/fisiologiaRESUMO
We analyze the performance of a quantum Otto cycle, employing a time-dependent harmonic oscillator as the working fluid undergoing sudden expansion and compression strokes during the adiabatic stages, coupled to a squeezed reservoir. First, we show that the maximum efficiency that our engine can achieve is 1/2 only, which is in contrast with earlier studies claiming unit efficiency under the effect of a squeezed reservoir. Then, in the high-temperature limit, we obtain analytic expressions for the upper bound on the efficiency as well as on the coefficient of performance of the Otto cycle. The obtained bounds are independent of the parameters of the system and depend on the reservoir parameters only. Additionally, with a hot squeezed thermal bath, we obtain an analytic expression for the efficiency at maximum work which satisfies the derived upper bound. Further, in the presence of squeezing in the cold reservoir, we specify an operational regime for the Otto refrigerator otherwise forbidden in the standard case. Finally, we find the cost of creating a squeezed state from the thermal state and show that in order to harvest the benefits of squeezing, it is sufficient to squeeze only one mode of the reservoir in resonance with the transition frequency of the working fluid. Further, we show that when the cost of squeezing is included in the definition of the operational efficiency of the engine, the advantages of squeezing fade away. Still, being purely quantum mechanical fuel in nature, squeezed reservoirs are beneficial in their own way by providing us with more compact energy storage medium or offering effectively high-temperature baths without being actually too hot.
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Network models of brain dynamics provide valuable insight into the healthy functioning of the brain and how this breaks down in disease. A pertinent example is the use of network models to understand seizure generation (ictogenesis) in epilepsy. Recently, computational models have emerged to aid our understanding of seizures and to predict the outcome of surgical perturbations to brain networks. Such approaches provide the opportunity to quantify the effect of removing regions of tissue from brain networks and thereby search for the optimal resection strategy. Here, we use computational models to elucidate how sets of nodes contribute to the ictogenicity of networks. In small networks we fully elucidate the ictogenicity of all possible sets of nodes and demonstrate that the distribution of ictogenicity across sets depends on network topology. However, the full elucidation is a combinatorial problem that becomes intractable for large networks. Therefore, we combine computational models with a genetic algorithm to search for minimal sets of nodes that contribute significantly to ictogenesis. We demonstrate the potential applicability of these methods in practice by identifying optimal sets of nodes to resect in networks derived from 20 individuals who underwent resective surgery for epilepsy. We show that they have the potential to aid epilepsy surgery by suggesting alternative resection sites as well as facilitating the avoidance of brain regions that should not be resected.
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We suggest alternative quantum Otto engines, using heat bath algorithmic cooling with a partner pairing algorithm instead of isochoric cooling and using quantum swap operations instead of quantum adiabatic processes. Liquid state nuclear magnetic resonance systems in a single entropy sink are treated as working fluids. The extractable work and thermal efficiency are analyzed in detail for four-stroke and two-stroke types of alternative quantum Otto engines. The role of the heat bath algorithmic cooling in these cycles is to use a single entropy sink instead of two so that a single incoherent energy resource can be harvested and processed using an algorithmic quantum heat engine. Our results indicate a path to programmable quantum heat engines as analogs of quantum computers beyond traditional heat engine cycles. We find that for our NMR system example implementation of quantum algorithmic heat engine stages yields more power due to increased cycle speeds.