204 research outputs found
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Low-voltage magnetoelectric coupling in Fe0.5Rh0.5/0.68PbMg1/3Nb2/3O3-0.32PbTiO3 thin-film heterostructures
The rapid development of computing applications demands novel low-energy consumption devices for information processing. Among various candidates, magnetoelectric heterostructures hold promise for meeting the required voltage and power goals. Here, a route to low-voltage control of magnetism in 30 nm FeRh/100 nm 0.68PbMgNbO-0.32PbTiO (PMN-PT) heterostructures is demonstrated wherein the magnetoelectric coupling is achieved via strain-induced changes in the FeRh mediated by voltages applied to the PMN-PT. We describe approaches to achieve high-quality, epitaxial growth of FeRh on the PMN-PT films and, a methodology to probe and quantify magnetoelectric coupling in small thin-film devices via studies of the anomalous Hall effect. By comparing the spin-flop field change induced by temperature and external voltage, the magnetoelectric coupling coefficient is estimated to reach â7 Ă 10 s m at 325 K while applying a â0.75 V bias
Folding Circular Permutants of IL-1ÎČ: Route Selection Driven by Functional Frustration
Interleukin-1ÎČ (IL-1ÎČ) is the cytokine crucial to inflammatory and immune response. Two dominant routes are populated in the folding to native structure. These distinct routes are a result of the competition between early packing of the functional loops versus closure of the ÎČ-barrel to achieve efficient folding and have been observed both experimentally and computationally. Kinetic experiments on the WT protein established that the dominant route is characterized by early packing of geometrically frustrated functional loops. However, deletion of one of the functional loops, the ÎČ-bulge, switches the dominant route to an alternative, yet, as accessible, route, where the termini necessary for barrel closure form first. Here, we explore the effect of circular permutation of the WT sequence on the observed folding landscape with a combination of kinetic and thermodynamic experiments. Our experiments show that while the rate of formation of permutant protein is always slower than that observed for the WT sequence, the region of initial nucleation for all permutants is similar to that observed for the WT protein and occurs within a similar timescale. That is, even permutants with significant sequence rearrangement in which the functional-nucleus is placed at opposing ends of the polypeptide chain, fold by the dominant WT âfunctional loop-packing routeâ, despite the entropic cost of having to fold the N- and C- termini early. Taken together, our results indicate that the early packing of the functional loops dominates the folding landscape in active proteins, and, despite the entropic penalty of coalescing the termini early, these proteins will populate an entropically unfavorable route in order to conserve function. More generally, circular permutation can elucidate the influence of local energetic stabilization of functional regions within a protein, where topological complexity creates a mismatch between energetics and topology in active proteins
Orbital overlap effects in electron transfer reactions across a metal nanowire/electrolyte solution interface
In this paper, we report on calculations of the orbital overlap between Fe(III) and Cr(III) aquacomplexes and different electrode surfaces: Cu(111), Ag (111), Au(111), Pt(111), and corresponding monatomic wires. The electronic structure of the monocrystalline surfaces and nanowires are described in terms of the electronic spillover and density of electronic states at the Fermi level obtained from periodic density functional theory (DFT) calculations. The transmission coefficients (Îș) characterizing the first stage of outer-sphere electron transfer for the reduction of aquacomplexes are calculated on the basis of LandauâZener theory as a function of electrodeâreactant separation; the electronic transmission coefficients for the [Cr(H2O)6]3+/2+ redox couple were found to be smaller than those for [Fe(H2O)6]3+/2+. Two different intervals can be clearly distinguished for Cu, Au and Pt: âa catalytic regionâ, where Îș(wire) > Îș(Me slab) and âan inhibition regionâ, where Îș(wire) < Îș(Me slab). A similar behavior exhibits the coupling constant estimated for a hydrogen atom adsorbed at the Au(111) surface and the Au monatomic wire. These effects originate from some specific features of electronic density profile for metal nanowires: at short distances the electronic density of nanowires is higher compared with the (111) metal surfaces, while at larger separations it decreases more sharply.Fil: Nazmutdinov, Renat R.. Kazan National Research Technological University; RusiaFil: Berezin, Alexander S.. Kazan National Research Technological University; RusiaFil: Soldano, GermĂĄn. Universitat Ulm; Alemania. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Schmickler, Wolfgang. Universitat Ulm; Alemani
A statistical learning strategy for closed-loop control of fluid flows
This work discusses a closed-loop control strategy for complex systems utilizing scarce and streaming data. A discrete embedding space is first built using hash functions applied to the sensor measurements from which a Markov process model is derived, approximating the complex systemâs dynamics. A control strategy is then learned using reinforcement learning once rewards relevant with respect to the control objective are identified. This method is designed for experimental configurations, requiring no computations nor prior knowledge of the system, and enjoys intrinsic robustness. It is illustrated on two systems: the control of the transitions of a Lorenzâ63 dynamical system, and the control of the drag of a cylinder flow. The method is shown to perform well
Plakophilin3 Loss Leads to an Increase in PRL3 Levels Promoting K8 Dephosphorylation, Which Is Required for Transformation and Metastasis
The desmosome anchors keratin filaments in epithelial cells leading to the formation of a tissue wide IF network. Loss of the desmosomal plaque protein plakophilin3 (PKP3) in HCT116 cells, leads to an increase in neoplastic progression and metastasis, which was accompanied by an increase in K8 levels. The increase in levels was due to an increase in the protein levels of the Phosphatase of Regenerating Liver 3 (PRL3), which results in a decrease in phosphorylation on K8. The increase in PRL3 and K8 protein levels could be reversed by introduction of an shRNA resistant PKP3 cDNA. Inhibition of K8 expression in the PKP3 knockdown clone S10, led to a decrease in cell migration and lamellipodia formation. Further, the K8 PKP3 double knockdown clones showed a decrease in colony formation in soft agar and decreased tumorigenesis and metastasis in nude mice. These results suggest that a stabilisation of K8 filaments leading to an increase in migration and transformation may be one mechanism by which PKP3 loss leads to tumor progression and metastasis
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Early Detection and Prediction of Cardiotoxicity in Chemotherapy-Treated Patients
As breast cancer survival increases, cardiotoxicity associated with chemotherapeutic regimens such as anthracyclines and trastuzumab becomes a more significant issue. Assessment of the left ventricular (LV) ejection fraction fails to detect subtle alterations in LV function. The objective of this study was to evaluate whether more sensitive echocardiographic measurements and biomarkers could predict future cardiac dysfunction in chemotherapy-treated patients. Forty-three patients diagnosed with breast cancer who received anthracyclines and trastuzumab therapy underwent echocardiography and blood sampling at 3 time points (baseline and 3 and 6 months during the course of chemotherapy). The LV ejection fraction; peak systolic myocardial longitudinal, radial, and circumferential strain; echocardiographic markers of diastolic function; N-terminal proâB-type natriuretic peptide; and high-sensitivity cardiac troponin I were measured. Nine patients (21%) developed cardiotoxicity (1 at 3 months and 8 at 6 months) as defined by the Cardiac Review and Evaluation Committee reviewing trastuzumab. A decrease in longitudinal strain from baseline to 3 months and detectable high-sensitivity cardiac troponin I at 3 months were independent predictors of the development of cardiotoxicity at 6 months. The LV ejection fraction, parameters of diastolic function, and N-terminal proâB-type natriuretic peptide did not predict cardiotoxicity. In conclusion, cardiac troponin plasma concentrations and longitudinal strain predict the development of cardiotoxicity in patients treated with anthracyclines and trastuzumab. The 2 parameters may be useful to detect chemotherapy-treated patients who may benefit from alternative therapies, potentially decreasing the incidence of cardiotoxicity and its associated morbidity and mortality
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