1,009 research outputs found

    Reinforcement Learning Based Output-Feedback Control of Nonlinear Nonstrict Feedback Discrete-Time Systems with Application to Engines

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    A novel reinforcement-learning based output-adaptive neural network (NN) controller, also referred as the adaptive-critic NN controller, is developed to track a desired trajectory for a class of complex nonlinear discrete-time systems in the presence of bounded and unknown disturbances. The controller includes an observer for estimating states and the outputs, critic, and two action NNs for generating virtual, and actual control inputs. The critic approximates certain strategic utility function and the action NNs are used to minimize both the strategic utility function and their outputs. All NN weights adapt online towards minimization of a performance index, utilizing gradient-descent based rule. A Lyapunov function proves the uniformly ultimate boundedness (UUB) of the closed-loop tracking error, weight, and observer estimation. Separation principle and certainty equivalence principles are relaxed; persistency of excitation condition and linear in the unknown parameter assumption is not needed. The performance of this adaptive critic NN controller is evaluated through simulation with the Daw engine model in lean mode. The objective is to reduce the cyclic dispersion in heat release by using the controller

    Global Energetics of Large Solar Eruptive Events

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    We have evaluated the energetics of the larger solar eruptive events recorded with a variety of spacecraft instruments between February 2002 and December 2006. All of the energetically important components of the flares and of the accompanying coronal mass ejections and solar energetic particles have been evaluated as accurately as the observations allow. These components include the following : (1) the total energy in the high temperature plasma determined from the RHESSI thermal X-ray observations; (2) the total energies in accelerated electrons above 20 keV and ions above 1 MeV from RHESSI hard X-ray and gamma-ray observations, respectively; (3) the potential and kinetic energies of the CME from SOHO/LASCO observations; (4) the solar energetic particle (SEP) energy estimates from in situ measurements on ACE, GOES, and SOHO; (5) the total radiated energy from the SORCEITSI measurements where available, and otherwise from the Flare Irradiance Spectral Model (FISM). The results are assimilated and discussed relative to the probable amount of non potential magnetic energy estimated to be available in the flaring active regions from MDI line-of-sight magnetograms

    Hydrogen-Based Metabolism as an Ancestral Trait in Lineages Sibling to the Cyanobacteria

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    © 2019, The Author(s). The evolution of aerobic respiration was likely linked to the origins of oxygenic Cyanobacteria. Close phylogenetic neighbors to Cyanobacteria, such as Margulisbacteria (RBX-1 and ZB3), Saganbacteria (WOR-1), Melainabacteria and Sericytochromatia, may constrain the metabolic platform in which aerobic respiration arose. Here, we analyze genomic sequences and predict that sediment-associated Margulisbacteria have a fermentation-based metabolism featuring a variety of hydrogenases, a streamlined nitrogenase, and electron bifurcating complexes involved in cycling of reducing equivalents. The genomes of ocean-associated Margulisbacteria encode an electron transport chain that may support aerobic growth. Some Saganbacteria genomes encode various hydrogenases, and others may be able to use O2 under certain conditions via a putative novel type of heme copper O2 reductase. Similarly, Melainabacteria have diverse energy metabolisms and are capable of fermentation and aerobic or anaerobic respiration. The ancestor of all these groups may have been an anaerobe in which fermentation and H2 metabolism were central metabolic features. The ability to use O2 as a terminal electron acceptor must have been subsequently acquired by these lineages

    Pharmacodynamic Modeling of Anti-Cancer Activity of Tetraiodothyroacetic Acid in a Perfused Cell Culture System

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    Unmodified or as a poly[lactide-co-glycolide] nanoparticle, tetraiodothyroacetic acid (tetrac) acts at the integrin αvβ3 receptor on human cancer cells to inhibit tumor cell proliferation and xenograft growth. To study in vitro the pharmacodynamics of tetrac formulations in the absence of and in conjunction with other chemotherapeutic agents, we developed a perfusion bellows cell culture system. Cells were grown on polymer flakes and exposed to various concentrations of tetrac, nano-tetrac, resveratrol, cetuximab, or a combination for up to 18 days. Cells were harvested and counted every one or two days. Both NONMEM VI and the exact Monte Carlo parametric expectation maximization algorithm in S-ADAPT were utilized for mathematical modeling. Unmodified tetrac inhibited the proliferation of cancer cells and did so with differing potency in different cell lines. The developed mechanism-based model included two effects of tetrac on different parts of the cell cycle which could be distinguished. For human breast cancer cells, modeling suggested a higher sensitivity (lower IC50) to the effect on success rate of replication than the effect on rate of growth, whereas the capacity (Imax) was larger for the effect on growth rate. Nanoparticulate tetrac (nano-tetrac), which does not enter into cells, had a higher potency and a larger anti-proliferative effect than unmodified tetrac. Fluorescence-activated cell sorting analysis of harvested cells revealed tetrac and nano-tetrac induced concentration-dependent apoptosis that was correlated with expression of pro-apoptotic proteins, such as p53, p21, PIG3 and BAD for nano-tetrac, while unmodified tetrac showed a different profile. Approximately additive anti-proliferative effects were found for the combinations of tetrac and resveratrol, tetrac and cetuximab (Erbitux), and nano-tetrac and cetuximab. Our in vitro perfusion cancer cell system together with mathematical modeling successfully described the anti-proliferative effects over time of tetrac and nano-tetrac and may be useful for dose-finding and studying the pharmacodynamics of other chemotherapeutic agents or their combinations

    Fundamentals of impulsive energy release in the corona

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    It is essential that there be coordinated and co-optimized observations in X-rays, gamma-rays, and EUV during the peak of solar cycle 26 (~2036) to significantly advance our understanding of impulsive energy release in the corona. The open questions include: What are the physical origins of space-weather events? How are particles accelerated at the Sun? How is impulsively released energy transported throughout the solar atmosphere? How is the solar corona heated? Many of the processes involved in triggering, driving, and sustaining solar eruptive events -- including magnetic reconnection, particle acceleration, plasma heating, and energy transport in magnetized plasmas -- also play important roles in phenomena throughout the Universe. This set of observations can be achieved through a single flagship mission or, with foreplanning, through a combination of major missions (e.g., the previously proposed FIERCE mission concept).Comment: White paper submitted to the Decadal Survey for Solar and Space Physics (Heliophysics) 2024-2033; 5 pages, 1 figur

    Photon wave functions, wave-packet quantization of light, and coherence theory

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    The monochromatic Dirac and polychromatic Titulaer-Glauber quantized field theories (QFTs) of electromagnetism are derived from a photon-energy wave function in much the same way that one derives QFT for electrons, that is, by quantization of a single-particle wave function. The photon wave function and its equation of motion are established from the Einstein energy-momentum-mass relation, assuming a local energy density. This yields a theory of photon wave mechanics (PWM). The proper Lorentz-invariant single-photon scalar product is found to be non-local in coordinate space, and is shown to correspond to orthogonalization of the Titulaer-Glauber wave-packet modes. The wave functions of PWM and mode functions of QFT are shown to be equivalent, evolving via identical equations of motion, and completely describe photonic states. We generalize PWM to two or more photons, and show how to switch between the PWM and QFT viewpoints. The second-order coherence tensors of classical coherence theory and the two-photon wave functions are shown to propagate equivalently. We give examples of beam-like states, which can be used as photon wave functions in PWM, or modes in QFT. We propose a practical mode converter based on spectral filtering to convert between wave packets and their corresponding biorthogonal dual wave packets.Comment: 34 pages, 3 figures, minor correction

    Tryptophan-Accelerated Electron Flow Through Proteins

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    Energy flow in biological structures often requires submillisecond charge transport over long molecular distances. Kinetics modeling suggests that charge-transfer rates can be greatly enhanced by multistep electron tunneling in which redox-active amino acid side chains act as intermediate donors or acceptors. We report transient optical and infrared spectroscopic experiments that quantify the extent to which an intervening tryptophan residue can facilitate electron transfer between distant metal redox centers in a mutant Pseudomonas aeruginosa azurin. CuI oxidation by a photoexcited ReI-diimine at position 124 on a histidine(124)-glycine(123)-tryptophan(122)-methionine(121) β strand occurs in a few nanoseconds, fully two orders of magnitude faster than documented for single-step electron tunneling at a 19 angstrom donor-acceptor distance

    Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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    This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

    SLC37A1 and SLC37A2 Are Phosphate-Linked, Glucose-6-Phosphate Antiporters

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    Blood glucose homeostasis between meals depends upon production of glucose within the endoplasmic reticulum (ER) of the liver and kidney by hydrolysis of glucose-6-phosphate (G6P) into glucose and phosphate (Pi). This reaction depends on coupling the G6P transporter (G6PT) with glucose-6-phosphatase-α (G6Pase-α). Only one G6PT, also known as SLC37A4, has been characterized, and it acts as a Pi-linked G6P antiporter. The other three SLC37 family members, predicted to be sugar-phosphate:Pi exchangers, have not been characterized functionally. Using reconstituted proteoliposomes, we examine the antiporter activity of the other SLC37 members along with their ability to couple with G6Pase-α. G6PT- and mock-proteoliposomes are used as positive and negative controls, respectively. We show that SLC37A1 and SLC37A2 are ER-associated, Pi-linked antiporters, that can transport G6P. Unlike G6PT, neither is sensitive to chlorogenic acid, a competitive inhibitor of physiological ER G6P transport, and neither couples to G6Pase-α. We conclude that three of the four SLC37 family members are functional sugar-phosphate antiporters. However, only G6PT/SLC37A4 matches the characteristics of the physiological ER G6P transporter, suggesting the other SLC37 proteins have roles independent of blood glucose homeostasis

    Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

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    Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN
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