Oxidative activation of guanylate cyclase by prostaglandin endoperoxides and fatty acid hydroperoxides

Purified prostaglandin endoperoxides (PGG₂ and PGH₂) and hydroperoxides (15-OOH-PGE₂) as well as fatty acid hydroperoxides (12-OOH-20∶4, 15-OOH-20∶4, and 13-OOH-18∶2) were examined as effectors of soluble splenic cell guanylate cyclase activity. The procedures employed for the preparation and purification of these components circumvented the use of diethyl ether which obscured effects of lipid effectors because of contaminants presumed to be ether peroxides which were stimulatory to the cyclase. Addition of prostaglandin endoperoxides or fatty acid hydroperoxides to the reaction mixture led to a time-dependent activation of guanylate cyclase activity; 2.5-to 5-fold stimulation was seen during the first 6 min. The degree of stimulation and rate of activation were dependent on the concentration of the fatty acid effector; when initial velocities (6 min) were assessed, half maximal stimulation was achieved in the range of 2 to 3 μM. However, by extending the incubation time to 90 min, similar maximal increases in specific activity could be achieved with 3 or 10 μM PGG₂ or PGH₂. Activation of guanylate cyclase upon addition of prostaglandin endoperoxides or fatty acid hydroperoxides was prevented or reversed by the thiol reductants dithiothreitol (3 to 5 mM) or gluthathione (10 to 15 mM). Na₂S₂O₄, not known as an effective reducing agent of disulfieds, prevented but was relatively ineffective in reversing activation after it had been induced by PGG₂. Pretreatment of the enzyme preparation with increasing concentrations of N-ethyl-maleimide in the range of 0.01 to 1.0 mM prevented activation by PGG₂ without effecting basal guanylate cyclase activity. These observations indicate that fatty acid hydroperoxides and prostaglandin endoperoxides promote activation of the cyclase by oxidation of enzyme-related thiol functions. In contrast, PGE₂, PGF_2α, hydroxy fatty acids (13-OH-18∶2, 12-OH-20∶4) as well as saturated (18∶0), monoenoic (18∶1), dienoic (18∶2), and tetraenoic (20∶4) fatty acids were ineffective in promoting cyclase activation in the range of 1 to 10 μM. Studies to identify the species of the rapidly metabolized prostaglandin endoperoxides that serve as effectors of the cyclase indicated that PGG₂ but not 15-OOH-PGE₂ (the major buffer-rearrangement product of PGG₂) is most likely an activator. In the case of PGH₂ a rapidly generated (30 sec) metabolite of PGH₂ was found which contained a hydroperoxy or endoperoxy functional group and was equally as effective as PGH₂ as an apparent activator of the enzyme. The combined effects of PGG₂ and dehydroascorbic acid, another class of activator, exhibited additivity with respect to the rate at which the time-dependent activation was induced. These results suggest that activation of soluble guanylate cyclase from splenic cells can be achieved by the oxidation of sulfhydryls that may be associated with specific hydrophobic sites of the enzyme or a related regulatory component.     

Complex dynamics in a threshold advertising model

During the last decade economic models of varying complexity have been studied by using the qualitative theory of nonlinear dynamical systems theory. The purpose of the present paper is to analyze an economic model which is as simple as possible but exhibits sufficient nonlinearity to admit chaotic orbits. A firm's market share is assumed to be influenced only by a simple threshold advertising rule. It turns out that such a simple rule may create complex behavioural patterns, i.e., periodic orbits of any length and even chaotic, seemingly unpredictable time paths. By using the package LOCBIF we are able to investigate for which model parameters chaos arises and how the transition from stable equilibrium to chaos occurs.This work has been financially supported by the Austrian Science Foundation, project No. 7783-PHY.     

Statische und kinetische Instabilitäten bei Bauwerken

In der Bautechnik treten oft, z. B. bei windbelasteten oder meerestechnischen Konstruktionen, statische oder dynamische Instabilitäten auf – manchmal auch ein Zusammenwirken (Interaktion) beider Mechanismen, wobei die Knick‐ oder Beuleigenformen durchaus verschieden von den entsprechenden Schwingungseigenformen sein können. Es soll dargestellt werden, wann die Stabilitätsuntersuchungen der Strukturen statisch durchgeführt werden dürfen und in welcher Form sich die Ergebnisse bei einer zusätzlichen dynamischen Belastung verändern. Static and dynamic instabilities of structures. In structural design e. g. under wind loads or offshore structures we often have static or dynamic instabilities sometimes also an interaction of both mechanisms, where the buckling modes may be different from the vibration modes. We want to recognize, whether the investigations may be static and how the results may alter by dynamic loads.     

Quantitative T 2 * assessment of acute and chronic myocardial ischemia/reperfusion injury in mice

Object

Imaging of myocardial infarct composition is essential to assess efficacy of emerging therapeutics. T ₂ ^* mapping has the potential to image myocardial hemorrhage and fibrosis by virtue of its short T ₂ ^* . We aimed to quantify T ₂ ^* in acute and chronic myocardial ischemia/reperfusion (I/R) injury in mice.

Materials and methods

I/R-injury was induced in C57BL/6 mice (n?=?9). Sham-operated mice (n?=?8) served as controls. MRI was performed at baseline, and 1, 7 and 28?days after surgery. MRI at 9.4?T consisted of Cine, T ₂ ^* mapping and late-gadolinium-enhancement (LGE). Mice (n?=?6) were histologically assessed for hemorrhage and collagen in the fibrotic scar.

Results

Baseline T ₂ ^* values were 17.1?±?2.0?ms. At day 1, LGE displayed a homogeneous infarct enhancement. T ₂ ^* in infarct (12.0?±?1.1?ms) and remote myocardium (13.9?±?0.8?ms) was lower than at baseline. On days 7 and 28, LGE was heterogeneous. T ₂ ^* in the infarct decreased to 7.9?±?0.7 and 6.4?±?0.7?ms, whereas T ₂ ^* values in the remote myocardium were 14.2?±?1.1 and 15.6?±?1.0?ms. Histology revealed deposition of iron and collagen in parallel with decreased T ₂ ^* .

Conclusion

T ₂ ^* values are dynamic during infarct development and decrease significantly during scar maturation. In the acute phase, T ₂ ^* values in infarcted myocardium differ significantly from those in the chronic phase. T ₂ ^* mapping was able to confirm the presence of a chronic infarction in cases where LGE was inconclusive. Hence, T ₂ ^* may be used to discriminate between acute and chronic infarctions.     

Energy cost and error performance of range-aware, anchor-free localization algorithms

Many applications that use sensor data from a wireless sensor network (WSN) require corresponding node position information as well. Therefore, it is not surprising that a common figure of merit for localization algorithms is the accuracy of the position estimate produced. Similarly, the amount of communication required by a localization algorithm is often of paramount interest as well since it is common knowledge that communication expends the most energy in a WSN. However, localization algorithms seldom characterize their communication cost. Furthermore, when they do it is often merely qualitative and is typically described as “expensive”. For two types of range-aware, anchor-free localization algorithms we found the opposite to be true. Rather than being expensive, the communication costs were quite modest. So much so that we maintain range-aware, anchor-free localization algorithms should be chosen on the basis of the accuracy required by the intended application independent of the communication cost.In this paper, we examine the effect of node degree, node distribution, range error and network size on distance error and communication cost for both incremental and concurrent versions of range-aware, anchor-free algorithms. The concurrent algorithm is twice as accurate as the incremental, but less efficient. Furthermore, node degree influences the energy cost of the algorithms the most, but neither algorithm uses more than a surprisingly small 0.8% of a 560 mA h battery. This result indicates less energy efficient localization algorithms can be tolerated, especially if they provide better accuracy. Furthermore, if energy does need to be conserved, there is not much savings available within the localization algorithm and savings must be found in other areas such as the MAC protocol or routing algorithm.     

Beyond graph neural networks with lifted relational neural networks

Machine Learning - We introduce a declarative differentiable programming framework, based on the language of Lifted Relational Neural Networks, where small parameterized logic programs are used to...     

Discovery of Real-Space Topological Ferroelectricity in Metallic Transition Metal Phosphides

Ferroelectric metals—with coexisting ferroelectricity and structural asymmetry—challenge traditional perceptions because free electrons screen electrostatic forces between ions, the driving force of breaking the spatial inversion symmetry. Despite ferroelectric metals having been unveiled one after another, topologically switchable polar objects with metallicity have never been identified so far. Here, the discovery of real-space topological ferroelectricity in metallic and non-centrosymmetric Ni₂P is reported. Protected by the rotation–inversion symmetry operation, it is found that the balanced polarity of alternately stacked polyhedra couples intimately with elemental valence states, which are verified using quantitative electron energy-loss spectroscopy. First-principles calculations reveal that an applied in-plane compressive strain creates a tunable bilinear double-well potential and reverses the polyhedral polarity on a unit-cell scale. The dual roles of nickel cations, including polar displacement inside polyhedral cages and a 3D bonding network, facilitate the coexistence of topological polarity with metallicity. In addition, the switchable in-plane polyhedral polarity gives rise to a spin–orbit-coupling-induced spin texture with large momentum-dependent spin splitting. These findings point out a new direction for exploring valence–polarity–spin correlative interactions via topological ferroelectricity in metallic systems with structural asymmetry.     

High-Order Numerical Methods for 2D Parabolic Problems in Single and Composite Domains

In this work, we discuss and compare three methods for the numerical approximation of constant- and variable-coefficient diffusion equations in both single and composite domains with possible discontinuity in the solution/flux at interfaces, considering (i) the Cut Finite Element Method; (ii) the Difference Potentials Method; and (iii) the summation-by-parts Finite Difference Method. First we give a brief introduction for each of the three methods. Next, we propose benchmark problems, and consider numerical tests—with respect to accuracy and convergence—for linear parabolic problems on a single domain, and continue with similar tests for linear parabolic problems on a composite domain (with the interface defined either explicitly or implicitly). Lastly, a comparative discussion of the methods and numerical results will be given.     

Physical Mechanisms behind the Field‐Cycling Behavior of HfO2‐Based Ferroelectric Capacitors

Novel hafnium oxide (HfO₂)‐based ferroelectrics reveal full scalability and complementary metal oxide semiconductor integratability compared to perovskite‐based ferroelectrics that are currently used in nonvolatile ferroelectric random access memories (FeRAMs). Within the lifetime of the device, two main regimes of wake‐up and fatigue can be identified. Up to now, the mechanisms behind these two device stages have not been revealed. Thus, the main scope of this study is an identification of the root cause for the increase of the remnant polarization during the wake‐up phase and subsequent polarization degradation with further cycling. Combining the comprehensive ferroelectric switching current experiments, Preisach density analysis, and transmission electron microscopy (TEM) study with compact and Technology Computer Aided Design (TCAD) modeling, it has been found out that during the wake‐up of the device no new defects are generated but the existing defects redistribute within the device. Furthermore, vacancy diffusion has been identified as the main cause for the phase transformation and consequent increase of the remnant polarization. Utilizing trap density spectroscopy for examining defect evolution with cycling of the device together with modeling of the degradation results in an understanding of the main mechanisms behind the evolution of the ferroelectric response.     

Quantum dots with a paramagnetic coating as a bimodal molecular imaging probe

MRI detectable and targeted quantum dots were developed. To that aim, quantum dots were coated with paramagnetic and pegylated lipids, which resulted in a relaxivity, r(1), of nearly 2000 mM(-1)s(-1) per quantum dot. The quantum dots were functionalized by covalently linking alphavbeta3-specific RGD peptides, and the specificity was assessed and confirmed on cultured endothelial cells. The bimodal character, the high relaxivity, and the specificity of this nanoparticulate probe make it an excellent contrast agent for molecular imaging purposes.