Abstract
The role of advanced glycation end products (AGEs) in promoting and/or exacerbating metabolic dysregulation is being increasingly recognized. AGEs are formed when reducing sugars ...nonenzymatically bind to proteins or lipids, a process that is enhanced by hyperglycemic and hyperlipidemic environments characteristic of numerous metabolic disorders including obesity, diabetes, and its complications. In this mini-review, we put forth the notion that AGEs span the spectrum from cause to consequence of insulin resistance and diabetes, and represent a “common soil” underlying the pathophysiology of these metabolic disorders. Collectively, the surveyed literature suggests that AGEs, both those that form endogenously as well as exogenous AGEs derived from environmental factors such as pollution, smoking, and “Western”-style diets, contribute to the pathogenesis of obesity and diabetes. Specifically, AGE accumulation in key metabolically relevant organs induces insulin resistance, inflammation, and oxidative stress, which in turn provide substrates for excess AGE formation, thus creating a feed-forward–fueled pathological loop mediating metabolic dysfunction.
Path integral (PI) control problems are a restricted class of non-linear control problems that can be solved formally as a Feynman–Kac PI and can be estimated using Monte Carlo sampling. In this ...contribution we review PI control theory in the finite horizon case. We subsequently focus on the problem how to compute and represent control solutions. We review the most commonly used methods in robotics and control. Within the PI theory, the question of how to compute becomes the question of importance sampling. Efficient importance samplers are state feedback controllers and the use of these requires an efficient representation. Learning and representing effective state-feedback controllers for non-linear stochastic control problems is a very challenging, and largely unsolved, problem. We show how to learn and represent such controllers using ideas from the cross entropy method. We derive a gradient descent method that allows to learn feed-back controllers using an arbitrary parametrisation. We refer to this method as the path integral cross entropy method or PICE. We illustrate this method for some simple examples. The PI control methods can be used to estimate the posterior distribution in latent state models. In neuroscience these problems arise when estimating connectivity from neural recording data using EM. We demonstrate the PI control method as an accurate alternative to particle filtering.
The optoelectronic properties of prototypal Telluride amorphous phase‐change materials (GeTe and Ge2Sb2Te5) are investigated from ab initio molecular dynamics simulations. Local tetrahedral germanium ...geometries are identified from topological angular constraint counting and this permits to relate exactly their contribution to targeted properties. The analysis of our computation reveals that the dominant population of tetrahedral Ge contributes to the tail of the valence and conduction band but with an increased electronic localization for the latter, whereas residual (essentially octahedral) geometries induce an overall constant localization at E>EF$E>E_F$ except close to the Fermi gap, where p electrons are largely delocalized. The detailed calculation of the atomic dipoles in the amorphous state indicates that tetrahedral Ge leads to lower momenta, especially in a‐GeTe, and corresponding Ge‐based correlations with Wannier centers also indicate the dual nature of the local geometries. These features which drive optical and dielectric contrast exemplify the unique properties of phase‐change materials, and represent an obvious breakdown of the well‐known Zachariasen rule stating that the short‐range order is similar in crystals and glasses.
Biodegradable plastics have emerged as an encouraging alternative to reduce the production of plastic waste, especially for agricultural mulches. However, degradation of these plastics in the field ...may involve the release of products from the mulch into the soil, before and during the in-soil biodegradation. The present work aims to assess the potential effects on two agricultural plant species (Lactuca sativa L. –lettuce-, and Lycopersicon esculentum Mill. -tomato) of extracts from biodegradable (BDMs: Mater-Bi, Bioplast-SP4 and SP-6, BioFilm, BioFlex, Ecovio, Mirel, Paper) and Polyethylene mulch films. A previously designed highly sensitive in vitro ecotoxicity test was used.
Some of the extracts from the biodegradable plastics had effects on plant development. Germination was reduced by Bioplast films treatments, both in lettuce (B-SP4) and in tomato (B-SP4 and B-SP-6). In lettuce, root development was notably reduced by all treatments except for Paper and Polyethylene. Plant aerial growth was also limited with Bioplast and BioFlex, but enhanced with Paper extracts. At a whole, tomato plants showed higher sensitivity than lettuce in the test. Tomato aerial plant part and root growth were reduced by all treatments with the exception of BioFlex and Polyethylene. For both plant species, inhibitory effects on development were associated to proline increases, a physiological marker for some plant stresses.
It can be concluded that the contact of unused biodegradable films with a water solution may result in changes in plant development that depend on the nature of the biodegradable film. The in vitro used test revealed to be a highly sensitive tool for ecotoxicity studies. These results are to contribute to design safe materials for agricultural applications.
•An in vitro test for ecotoxicity in cultivated plants has been developed.•Lettuce and tomato are sensitive to compounds released from biodegradable mulches.•Germination and plant growth do not equally respond to the test.•Compounds released from biodegradable plastic mulches may have strong inhibitory effects on plant root development.•Proline is proposed as stress marker for compounds released from biodegradable plastic mulches.
Abstract
When compared with rare-earth coated conductors, magnesium diboride superconducting cables are known to show significant advantages by cost and easy production. However, the inherent ...difficulty for achieving a significant reduction of their magnetization losses in multifilamentary wires, without degrading the high critical current density that is so characteristic of the monowire, is considered as one of the major drawbacks for their practical use in high power density applications. Being this one of the major markets for superconducting cables, from fundamental principles and computational optimization techniques, in this paper we demonstrate how the embedding of the superconducting filaments into soft-ferromagnetic metastructures can render to their full magnetic decoupling, and therefore, to the maximum reduction of the energy losses that can be achieved without deteriorate the critical current density of the cable. The designed multifilamentary metastructure is made of NbTi coated MgB
2
superconducting filaments in a Cu-matrix, serving as a reference for validating our model with actual experimental measurements in monowires and multifilamentary wires. The novelty in our computationally aided multifilamentary wires, is that each one of the filaments is embedded within a thin metastructure made of a soft-ferromagnetic layer and a resistive layer. We have found that for soft-ferromagnetic layers with magnetic permeabilities in the range of
$$\mu _{r}=$$
μ
r
=
20–100, nearly a full magnetic decoupling between the superconducting filaments can be achieved, leading to efficiencies higher than
$$92\%$$
92
%
, and an overall reduction of the AC-losses (including eddy currents at the Cu-matrix) higher than
$$50\%$$
50
%
.
With the recent progresses on the designing and manufacturing of lightweight superconducting cables with high engineering current density, the need for a reliable, fast, and accurate computational ...model forecasting the alternating current (AC) losses of cold-dielectric conductors is pivotal for power grid investors and operators. However, validating such models is not an easy task. This is due to the low availability of experimental data for large scale power cables, and likewise, because of the large computational burden which underlies the total number of second generational high temperature superconducting (2G-HTS) tapes in the modelling of realistic power cables. Thus, aiming to overcome these challenges, we present a detailed two-dimensional H-model capable to reproduce the experimentally measured AC-losses of multi-layer power cables made of tens of 2G-HTS tapes. Two cable designs with very high critical currents (<inline-formula><tex-math notation="LaTeX">\text{1.7}~kA</tex-math></inline-formula> and <inline-formula><tex-math notation="LaTeX">\text{3.2}~kA</tex-math></inline-formula>) have been considered. These are composed of five and six concentric layers wound over a cylindrical former consisting of 50 and 67 2G-HTS tapes, respectively. In both situations a remarkable resemblance between the simulations and experiments has been found, offering a unique view of the local electrodynamics of the wound tapes where the mechanisms of shielding, magnetization, and transport currents coexist within the hysteretic process.
Protein expression and selection is an essential process in the modification of biological products. Expressed proteins are selected based on desired traits (phenotypes) from diverse gene libraries ...(genotypes), whose size may be limited due to the difficulties inherent in diverse cell preparation. In addition, not all genes can be expressed in cells, and linking genotype with phenotype further presents a great challenge in protein engineering. We present a DNA gel-based platform that demonstrates the versatility of two DNA microgel formats to address fundamental challenges of protein engineering, including high protein yield, isolation of gene sets, and protein display. We utilize microgels to show successful protein production and capture of a model protein, green fluorescent protein (GFP), which is further used to demonstrate a successful gene enrichment through fluorescence-activated cell sorting (FACS) of a mixed population of microgels containing the GFP gene. Through psoralen cross-linking of the hydrogels, we have synthesized DNA microgels capable of surviving denaturing conditions while still possessing the ability to produce protein. Lastly, we demonstrate a method of producing extremely high local gene concentrations of up to 32 000 gene repeats in hydrogels 1 to 2 μm in diameter. These DNA gels can serve as a novel cell-free platform for integrated protein expression and display, which can be applied toward more powerful, scalable protein engineering and cell-free synthetic biology with no physiological boundaries and limitations.
The Receptor for Advanced Glycation End Products (RAGE) is expressed by multiple cell types in the brain and spinal cord that are linked to the pathogenesis of neurovascular and neurodegenerative ...disorders, including neurons, glia (microglia and astrocytes) and vascular cells (endothelial cells, smooth muscle cells and pericytes). Mounting structural and functional evidence implicates the interaction of the RAGE cytoplasmic domain with the formin, Diaphanous1 (DIAPH1), as the key cytoplasmic hub for RAGE ligand-mediated activation of cellular signaling. In aging and diabetes, the ligands of the receptor abound, both in the central nervous system (CNS) and in the periphery. Such accumulation of RAGE ligands triggers multiple downstream events, including upregulation of RAGE itself. Once set in motion, cell intrinsic and cell-cell communication mechanisms, at least in part via RAGE, trigger dysfunction in the CNS. A key outcome of endothelial dysfunction is reduction in cerebral blood flow and increased permeability of the blood brain barrier, conditions that facilitate entry of activated leukocytes into the CNS, thereby amplifying primary nodes of CNS cellular stress. This contribution details a review of the ligands of RAGE, the mechanisms and consequences of RAGE signal transduction, and cites multiple examples of published work in which RAGE contributes to the pathogenesis of neurovascular perturbation. Insights into potential therapeutic modalities targeting the RAGE signal transduction axis for disorders of CNS vascular dysfunction and neurodegeneration are also discussed.
•RAGE is linked to the pathogenesis of neurovascular and neurodegenerative disorders.•RAGE-mediated cell-intrinsic and cell-cell network mechanisms cause CNS dysfunction.•RAGE plays roles in endothelial, neuronal and glial dysfunction in the CNS.•Targeting RAGE may be beneficial in neurovascular and neurodegenerative disorders.
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•Complex coacervation between WPI-KC using a US pretreatment was achieved.•Despite WPI structure change by US treatment, coacervation with carrageenan remains.•Functional properties ...improvement was observed in US pretreated complex coacervates.
The aim of this work was to evaluate the influence of high-intensity ultrasound (HIUS) treatment on whey protein isolate (WPI) molecular structure as a previous step for complex coacervation (CC) with kappa-carrageenan (KC) and its influence on CC functional properties. Protein suspension of WPI (1% w/w) was treated with an ultrasound probe (24 kHz, 2 and 4 min, at 50 and 100% amplitude), non HIUS pretreated WPI was used as a control. Coacervation was achieved by mixing WPI and KC dispersions (10 min). Time and amplitude of the sonication treatment had a direct effect on the molecular structure of the protein, FTIR-ATR analysis detected changes on pretreated WPI secondary structure (1600–1700 cm−1) after sonication. CC electrostatic interactions were detected between WPI positive regions, KC sulfate group (1200–1260 cm−1), and the anhydrous oxygen of the 3,6 anhydro-D-galactose (940–1066 cm−1) with a partial negative charge. After ultrasound treatment, a progressive decrease in WPI particle size (nm) was detected. Rheology results showed pseudoplastic behavior for both, KC and CC, with a significant change on the viscosity level. Further, volume increment, stability, and expansion percentages of CC foams were improved using WPI sonicated. Besides, HIUS treatment had a positive effect on the emulsifying properties of the CC, increasing the time emulsion stability percentage. HIUS proved to be an efficient tool to improve functional properties in WPI-KC CC.
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