Nonintegrable Systems Research Articles

Power, efficiency, and fluctuations in steady-state heat engines.

We consider the quality factor Q, which quantifies the trade-off between power, efficiency, and fluctuations in steady-state heat engines modeled by dynamical systems. We show that the nonlinear scattering theory, in both classical and quantum mechanics, sets the bound Q=3/8 when approaching the Carnot efficiency. On the other hand, interacting, nonintegrable, and momentum-conserving systems can achieve the value Q=1/2, which is the universal upper bound in linear response. This result shows that interactions are necessary to achieve the optimal performance of a steady-state heat engine.

Generation of an iPSC line (AKOSi006-A) from fibroblasts of an NPC1 patient, carrying the homozygous mutation p.I1061T (c.3182T>C) and a control iPSC line (AKOSi007-A) using a non-integrating Sendai virus system.

Niemann-Pick disease type C1 (NPC1) is a rare inherited lipid storage disorder caused by mutations in the NPC1 gene. Mutations lead to impaired lipid trafficking and subsequently to accumulation of cholesterol and sphingolipids. NPC1-patients present variable multisystemic symptoms, including neurological deficits. Here, we describe the generation of human iPSC lines obtained from fibroblasts of a male individual, carrying the homozygous mutation p.I1061T, and an unrelated and healthy male individual. A non-integrating Sendai virus system, containing KLF4, OCT3/4, SOX2 and C-MYC, was used for reprogramming. These cell lines provide a valuable resource for studying the pathophysiology of multisystemic NPC1-disease.

Taking snapshots of a quantum thermalization process: Emergent classicality in quantum jump trajectories.

We investigate theoretically the emergence of classical statistical physics in a finite quantum system that is either totally isolated or otherwise subjected to a quantum measurement process. We show via a random matrix theory approach to nonintegrable quantum systems that the set of outcomes of the measurement of a macroscopic observable evolve in time like stochastic variables, whose variance satisfies the celebrated Einstein relation for Brownian diffusion. Our results show how to extend the framework of eigenstate thermalization to the prediction of properties of quantum measurements on an otherwise closed quantum system. We show numerically the validity of the random matrix approach in quantum chain models.

Optimized Approaches for the Induction of Putative Canine Induced Pluripotent Stem Cells from Old Fibroblasts Using Synthetic RNAs.

Simple SummaryA non-integrating and self-replicating Venezuelan equine encephalitis RNA replicon system can potentially make a great contribution to the generation of clinically applicable canine induced pluripotent stem cells. Our study shows a new method to utilize the synthetic RNA-based approach for canine somatic cell reprogramming regarding transfection and reprogramming efficiency.Canine induced pluripotent stem cells (ciPSCs) can provide great potential for regenerative veterinary medicine. Several reports have described the generation of canine somatic cell-derived iPSCs; however, none have described the canine somatic cell reprogramming using a non-integrating and self-replicating RNA transfection method. The purpose of this study was to investigate the optimal strategy using this approach and characterize the transition stage of ciPSCs. In this study, fibroblasts obtained from a 13-year-old dog were reprogrammed using a non-integrating Venezuelan equine encephalitis (VEE) RNA virus replicon, which has four reprogramming factors (collectively referred to as T7-VEE-OKS-iG and comprised of hOct4, hKlf4, hSox2, and hGlis1) and co-transfected with the T7-VEE-OKS-iG RNA and B18R mRNA for 4 h. One day after the final transfection, the cells were selected with puromycin (0.5 µg/mL) until day 10. After about 25 days, putative ciPSC colonies were identified showing TRA-1-60 expression and alkaline phosphatase activity. To determine the optimal culture conditions, the basic fibroblast growth factor in the culture medium was replaced with a modified medium supplemented with murine leukemia inhibitory factor (mLIF) and two kinase inhibitors (2i), PD0325901(MEK1/2 inhibitor) and CHIR99021 (GSK3β inhibitor). The derived colonies showed resemblance to naïve iPSCs in their morphology (dome-shaped) and are dependent on mLIF and 2i condition to maintain an undifferentiated phenotype. The expression of endogenous pluripotency markers such as Oct4, Nanog, and Rex1 transcripts were confirmed, suggesting that induced ciPSCs were in the late intermediate stage of reprogramming. In conclusion, the non-integrating and self-replicating VEE RNA replicon system can potentially make a great contribution to the generation of clinically applicable ciPSCs, and the findings of this study suggest a new method to utilize the VEE RNA approach for canine somatic cell reprogramming.

Generation of a human induced pluripotent stem cell line (CPGHi001-A) from a hearing loss patient with the TMC1 p.M418K mutation.

By using a nonintegrating plasmid delivery system, we generated induced pluripotent stem cells (iPSCs) from the urine cells of a male patient from the family carrying the TMC1 p.M418K mutation. This mutation is homologous to that in Beethoven mice, which were treated by gene editing successfully. The resulting iPSCs had a normal karyotype, showed pluripotency by immunofluorescence staining, and differentiated into the three germ layers in vivo. This cellular model will provide a useful platform for investigating the pathogenic mechanisms of TMC1-related deafness, further laying the foundation for clinical transformation applications and providing a reference for the final gene therapy in humans.

Generation and characterization of two iPSC lines from human adipose tissue-derived stem cells of healthy donors.

Here we have generated two induced pluripotent stem cell (iPSC) lines, hASC-iPSC-1A and hASC-iPSC-2A, by reprogramming human adipose tissue derived stem cells of 28 and 23years old healthy donors. Reprogramming was achieved using nonintegrative Sendai viral vector system containing the reprogramming factors Klf4, Oct3/4, Sox2, c-Myc. Though the karyotypes of these cells were normal (46, XX) and (46, XY), their pluripotency potentials were confirmed by the expression of factors of pluripotency markers in vitro and teratoma formation in vivo. These iPSCs differentiated cells can serve as control for disease modeling and drug screening.

Generation of Human Induced Pluripotent Stem Cells and Differentiation into Cardiomyocytes.

Failure to regenerate myocardium after injury is a major cause of mortality and morbidity in humans. Direct differentiation of human induced pluripotent stem cells (iPSCs) into cardiomyocytes provides an invaluable resource to pursue cardiac regeneration based on cellular transplantation. Beyond the potential for clinical therapies, iPSC technology also enables the generation of cardiomyocytes to recapitulate patient-specific phenotypes, thus presenting a powerful in vitro cell-based model to understand disease pathology and guide precision medicine. Here, we describe protocols for reprogramming of human dermal fibroblasts and blood cells into iPSCs using the non-integrative Sendai virus system and for the monolayer differentiation of iPSCs to cardiomyocytes using chemically defined media.

Computing solitary wave solutions of coupled nonlinear Hirota and Helmholtz equations

In this article, we obtain the exact solutions two coupled models, one integrable system, namely coupled nonlinear Hirota (CNHI) equation and another non-integrable system, namely coupled nonlinear Helmholtz (CNHE) equation via the exp (−Φ(ε))–expansion method. The obtained travelling wave solutions are structured in rational, trigonometric and hyperbolic functions. These solutions lead to diverse types of solitary optical waves for free choices of parameters that guarantee the sustainability of such solutions. Also, 3D illustrations for the free choices of the physical parameters is provided to understand the physical explanation of the problems. These results further enrich and deepen the understanding of the dynamics of higher-dimensional soliton propagation.

Quantum chaos as delocalization in Krylov space

We show in full generality that time-correlation function of a physical observable analytically continued to imaginary time is a tau-function of integrable Toda hierarchy. Using this relation we show that the singularity along the imaginary axis, which is a generic behavior for quantum non-integrable many-body system, is due to delocalization in Krylov space.

Sequential Combustion in Steam Methane Reformers for Hydrogen and Power Production With CCUS in Decarbonized Industrial Clusters

In future energy supply systems, hydrogen and electricity may be generated in decarbonized industrial clusters using a common infrastructure for natural gas supply, electricity grid and transport and geological storage of CO2. The novel contribution of this article consists of using sequential combustion in a steam methane reforming (SMR) hydrogen plant to allow for capital and operating cost reduction by using a single post-combustion carbon capture system for both the hydrogen process and the combined cycle gas turbine (CCGT) power plant, plus appropriate integration for this new equipment combination. The concept would be widely applied to any post-combustion CO2 capture process. A newly developed, rigorous, gPROMs model of two hydrogen production technologies, covering a wide range of hydrogen production capacities, thermodynamically integrated with commercially available gas turbine engines quantifies the step change in thermal efficiency and hydrogen production efficiency. It includes a generic post-combustion capture technology – a conventional 30%wt MEA process - to quantify the reduction in size of CO2 absorber columns, the most capital intensive part of solvent-based capture systems. For a conventional SMR located downstream of an H-class gas turbine engine, followed by a three-pressure level HRSG and a capture plant with two absorbers, the integrated system produces ca. 696,400 Nm3/h of H2 with a net power output of 651 MWe at a net thermal efficiency of 38.9%LHV. This corresponds to 34 MWe of additional power, increasing efficiency by 4.9% points, and makes one absorber redundant compared to the equivalent non-integrated system producing the same volume of H2. For a dedicated gas heated reformer (GHR) located downstream of an aeroderivative gas turbine engine, followed by a two-pressure level HRSG and a capture plant with one absorber, the integrated system produces ca. 80,750 Nm3/h of H2 with a net power output of 73 MWe and a net thermal efficiency of 54.7%LHV. This corresponds to 13 MWe of additional power output, increasing efficiency by 13.5% points and also makes one absorber redundant. The article also presents new insights for the design and operation of reformers integrated with gas turbines and with CO2 capture.

To construct lumps, breathers and interaction solutions of arbitrary higher-order for a (4 + 1)-dimensional Fokas equation

In this work, by introducing a kind of parameters constraint to ensure that the well known formula of [Formula: see text]-soliton solutions works well not only for integrable systems, but also for non-integrable systems. Then for the [Formula: see text]-dimensional Fokas equation, based on this constraint and the modified [Formula: see text]-soliton solutions, we further construct its different types of higher-order wave solutions, especially new types of interaction solutions.

Exciting rogue waves, breathers, and solitons in coherent atomic media

We propose a scheme that excites rogue waves via electromagnetically induced transparency (EIT), which can also excite breathers and solitons. The system is a resonant Λ-type atomic ensemble. Under EIT conditions, the envelope equation of the probe field can be reduced to several different models, such as the saturable nonlinear Schrödinger equation (SNLSE), and SNLSE with the trapping potential provided by a far-detuned laser field or a magnetic field. In this scheme, rogue waves can be generated by different initial pulses, such as the Gaussian wave with (or without) the uniform background. The scheme can be used to obtain rogue waves, breathers and solitons. We show the existence regions of rogue waves, breathers, and solitons as the function of the amplitude and width of the initial pulse. The novelty of our paper is that, we not only show rogue waves in the integrable system numerically, but also present the method to generate and control rogue waves in the non-integrable system.

Nucleosides Rescue Replication-Mediated Genome Instability of Human Pluripotent Stem Cells.

SummaryHuman pluripotent stem cells (PSCs) are subject to the appearance of recurrent genetic variants on prolonged culture. We have now found that, compared with isogenic differentiated cells, PSCs exhibit evidence of considerably more DNA damage during the S phase of the cell cycle, apparently as a consequence of DNA replication stress marked by slower progression of DNA replication, activation of latent origins of replication, and collapse of replication forks. As in many cancers, which, like PSCs, exhibit a shortened G1 phase and DNA replication stress, the resulting DNA damage may underlie the higher incidence of abnormal and abortive mitoses in PSCs, resulting in chromosomal non-dysjunction or cell death. However, we have found that the extent of DNA replication stress, DNA damage, and consequent aberrant mitoses can be substantially reduced by culturing PSCs in the presence of exogenous nucleosides, resulting in improved survival, clonogenicity, and population growth.

Characterizing complexity of many-body quantum dynamics by higher-order eigenstate thermalization

Complexity of dynamics is at the core of quantum many-body chaos and exhibits a hierarchical feature: higher-order complexity implies more chaotic dynamics. Conventional ergodicity in thermalization processes is a manifestation of the lowest order complexity, which is represented by the eigenstate thermalization hypothesis (ETH) stating that individual energy eigenstates are thermal. Here, we propose a higher-order generalization of the ETH, named the $ k $-ETH ($ k=1,2,\dots $), to quantify higher-order complexity of quantum many-body dynamics at the level of individual energy eigenstates, where the lowest order ETH (1-ETH) is the conventional ETH. As a non-trivial contribution of the higher-order ETH, we show that the $ k $-ETH with $ k\geq 2 $ implies a universal behavior of the $ k $th Renyi entanglement entropy of individual energy eigenstates. In particular, the Page correction of the entanglement entropy originates from the higher-order ETH, while as is well known, the volume law can be accounted for by the 1-ETH. We numerically verify that the 2-ETH approximately holds for a nonintegrable system, but does not hold in the integrable case. To further investigate the information-theoretic feature behind the $ k $-ETH, we introduce a concept named a partial unitary $ k $-design (PU $ k $-design), which is an approximation of the Haar random unitary up to the $ k $th moment, where partial means that only a limited number of observables are accessible. The $ k $-ETH is a special case of a PU $ k $-design for the ensemble of Hamiltonian dynamics with random-time sampling. In addition, we discuss the relationship between the higher-order ETH and information scrambling quantified by out-of-time-ordered correlators. Our framework provides a unified view on thermalization, entanglement entropy, and unitary $ k $-designs, leading to deeper characterization of higher-order quantum complexity.

Generation of human iPS cell line IBCHi002-A from spinocerebellar ataxia type 3/Machado-Joseph disease patient's fibroblasts.

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is autosomal-dominant neurodegenerative disease caused by an expansion of polyglutamine-encoding CAG repeats in the ATXN3 gene. Here we established IBCHi002-A induced pluripotent stem cells (iPSCs) line generated from SCA3 patient fibroblasts by using non-integrative Sendai-virus delivery system of four reprogramming factors. This cellular model provides a valid platform for study SCA3 pathogenesis and potential therapies for this so far incurable disease.

Interactions of solitary waves in integrable and nonintegrable lattices.

We study how the dynamics of solitary wave (SW) interactions in integrable systems is different from that in nonintegrable systems in the context of crossing of two identical SWs in the (integrable) Toda and the (non-integrable) Hertz systems. We show that the collision process in the Toda system is perfectly symmetric about the collision point, whereas in the Hertz system, the collision process involves more complex dynamics. The symmetry in the Toda system forbids the formation of secondary SWs (SSWs), while the absence of symmetry in the Hertz system allows the generation of SSWs. We next show why the experimentally observed by-products of SW-SW interactions, the SSWs, must form in the Hertz system. We present quantitative estimations of the amount of energy that transfers from the SW after collision to the SSWs using (i) dynamical simulations, (ii) a phenomenological approach using energy and momentum conservation, and (iii) using an analytical solution introduced earlier to describe the SW in the Hertz system. We show that all three approaches lead to reliable estimations of the energy in the SSWs.

Quantitative behavior of non-integrable systems. II

Quantitative behavior of non-integrable systems. II

Quantum Joule expansion of one-dimensional systems

We investigate the Joule expansion of nonintegrable quantum systems that contain bosons or spinless fermions in one-dimensional lattices. A barrier initially confines the particles to be in half of the system in a thermal state described by the canonical ensemble and is removed at time $t = 0$. We investigate the properties of the time-evolved density matrix, the diagonal ensemble density matrix and the corresponding canonical ensemble density matrix with an effective temperature determined by the total energy conservation using exact diagonalization. The weights for the diagonal ensemble and the canonical ensemble match well for high initial temperatures that correspond to negative effective final temperatures after the expansion. At long times after the barrier is removed, the time-evolved R\'enyi entropy of subsystems bigger than half can equilibrate to the thermal entropy with exponentially small fluctuations. The time-evolved reduced density matrix at long times can be approximated by a thermal density matrix for small subsystems. Few-body observables, like the momentum distribution function, can be approximated by a thermal expectation of the canonical ensemble with strongly suppressed fluctuations. The negative effective temperatures for finite systems go to nonnegative temperatures in the thermodynamic limit for bosons, but is a true thermodynamic effect for fermions, which is confirmed by finite temperature density matrix renormalization group calculations. We propose the Joule expansion as a way to dynamically create negative temperature states for fermion systems with repulsive interactions.

Effective Differentiation and Biological Characterization of Retinal Pigment Epithelium Derived from Human Induced Pluripotent Stem Cells

ABSTRACT Purpose Human induced pluripotent stem cells (hiPSC)-derived retinal pigment epithelium (RPE) cells are therapeutic cells that have been shown to be promising in the rescue of lost photoreceptors. In this study, we generated hiPSC from human epidermal keratinocytes and subsequently differentiated them into RPE cells to investigate their ability to influence the retinal functions of the Royal College of Surgeon (RCS) rats. Methods Keratinocytes were reprogrammed to hiPSC using a non-integrating Sendai reprogramming system. Established hiPSCs were differentiated into RPE cells, and complete characterization was performed. Next, the suspension of hiPSC-RPE cells was transplanted into the subretinal space of 3-week-old RCS rats (n = 12). Posttransplantation evaluations were performed using optical coherence tomography (OCT), electroretinography, and immunohistochemical analysis. Results The hiPSC colonies were identical to embryonic stem-like cells that revealed the expression of pluripotency markers and retention of the normal genome. These cells exhibited the ability to differentiate into an amalgam of germ layers and produce RPE cells. The differentiated RPE cells exhibited an identical pigmented morphology that expressed RPE-specific markers, such as CRALBP, BESTROPHIN, RPE65, and MERTK. At 8 weeks of longitudinal culture, the RPE cells exhibited maximum pigmentation with in vitro phagocytotic activity. Furthermore, transplantation data showed improved retinal function till week 12 post-transplantation and a significantly higher number of rod/cone ratios in transplanted eyes compared to non-surgery control eyes. Conclusion hiPSC-derived RPE cells exhibited naïve RPE cell properties and functionality that provided trophic support and the transient rescue of photoreceptor cells.

Quantitative behavior of non-integrable systems. I

The theory of Uniform Distribution started with the equidistribution of the irrational rotation of the circle, proved around 1905 independently by Bohl, Sierpinski and Weyl. The quantitative upgrading of this qualitative result was done by Hardy, Littlewood, Ostrowski, Weyl, and others around 1920. Their work pointed out the crucial role of continued fractions in uniform distribution (for a good treatment of this, see e.g. the book of Drmota–Tichy [11]). This quantitative theory immediately solves—via “discretization”—the problem of quantitative equidistribution of the torus line flow in a square. Due to a simple equivalence, the torus line also settles the case of all “integrable” flat dynamical systems. In the last forty years a group of (mostly) ergodic theorists worked out a qualitative theory of nonintegrable flat systems (see Section 2.1). Using a new nonergodic approach that we call “shortline method”, here we start to develop a quantitative theory of nonintegrable flat dynamical systems. In this long work—which is a series of several papers—we discuss the similarities and the fundamental quantitative differences between “integrable” and “nonintegrable” systems.