Current computational methods for validating experimental network datasets compare overlap, i.e., shared links, with a reference network using a negative benchmark. However, this fails to quantify ...the level of agreement between the two networks. To address this, we propose a positive statistical benchmark to determine the maximum possible overlap between networks. Our approach can efficiently generate this benchmark in a maximum entropy framework and provides a way to assess whether the observed overlap is significantly different from the best-case scenario. We introduce a normalized overlap score, Normlap, to enhance comparisons between experimental networks. As an application, we compare molecular and functional networks, resulting in an agreement network of human as well as yeast network datasets. The Normlap score can improve the comparison between experimental networks by providing a computational alternative to network thresholding and validation.
Despite exceptional experimental efforts to map out the human interactome, the continued data incompleteness limits our ability to understand the molecular roots of human disease. Computational tools ...offer a promising alternative, helping identify biologically significant, yet unmapped protein-protein interactions (PPIs). While link prediction methods connect proteins on the basis of biological or network-based similarity, interacting proteins are not necessarily similar and similar proteins do not necessarily interact. Here, we offer structural and evolutionary evidence that proteins interact not if they are similar to each other, but if one of them is similar to the other's partners. This approach, that mathematically relies on network paths of length three (L3), significantly outperforms all existing link prediction methods. Given its high accuracy, we show that L3 can offer mechanistic insights into disease mechanisms and can complement future experimental efforts to complete the human interactome.
Uremic cardiomyopathy is characterized by diastolic dysfunction (DD), left ventricular hypertrophy (LVH), and fibrosis. Angiotensin-II plays a major role in the development of uremic cardiomyopathy ...via nitro-oxidative and inflammatory mechanisms. In heart failure, the beta-3 adrenergic receptor (β3-AR) is up-regulated and coupled to endothelial nitric oxide synthase (eNOS)-mediated pathways, exerting antiremodeling effects. We aimed to compare the antiremodeling effects of the angiotensin-II receptor blocker losartan and the β3-AR agonist mirabegron in uremic cardiomyopathy. Chronic kidney disease (CKD) was induced by 5/6th nephrectomy in male Wistar rats. Five weeks later, rats were randomized into four groups: (1) sham-operated, (2) CKD, (3) losartan-treated (10 mg/kg/day) CKD, and (4) mirabegron-treated (10 mg/kg/day) CKD groups. At week 13, echocardiographic, histologic, laboratory, qRT-PCR, and Western blot measurements proved the development of uremic cardiomyopathy with DD, LVH, fibrosis, inflammation, and reduced eNOS levels, which were significantly ameliorated by losartan. However, mirabegron showed a tendency to decrease DD and fibrosis; but eNOS expression remained reduced. In uremic cardiomyopathy, β3-AR, sarcoplasmic reticulum ATPase (SERCA), and phospholamban levels did not change irrespective of treatments. Mirabegron reduced the angiotensin-II receptor 1 expression in uremic cardiomyopathy that might explain its mild antiremodeling effects despite the unchanged expression of the β3-AR.
The internal and lattice structures of magnetic Skyrmions in B20-type FeGe are investigated using off-axis electron holography. The temperature, magnetic field, and angular dependence of the magnetic ...moments of individual Skyrmions are analyzed. The internal Skyrmion shape is found to vary with applied magnetic field. In contrast, the inter-Skyrmion distance remains almost unchanged in the lattice phase over the studied range of applied field. The amplitude of the local magnetic moment is found to vary with temperature, while the Skyrmion shape does not change significantly. Deviations from a circular to a hexagonal Skyrmion structure are observed in the lattice phase, in agreement with the results of micromagnetic simulations.
Gas clouds in present-day galaxies are inefficient at forming stars. Low star-formation efficiency is a critical parameter in galaxy evolution: it is why stars are still forming nearly 14 billion ...years after the Big Bang and why star clusters generally do not survive their births, instead dispersing to form galactic disks or bulges. Yet the existence of ancient massive bound star clusters (globular clusters) in the Milky Way suggests that efficiencies were higher when they formed ten billion years ago. A local dwarf galaxy, NGC 5253, has a young star cluster that provides an example of highly efficient star formation. Here we report the detection of the J = 3→2 rotational transition of CO at the location of the massive cluster. The gas cloud is hot, dense, quiescent and extremely dusty. Its gas-to-dust ratio is lower than the Galactic value, which we attribute to dust enrichment by the embedded star cluster. Its star-formation efficiency exceeds 50 per cent, tenfold that of clouds in the Milky Way. We suggest that high efficiency results from the force-feeding of star formation by a streamer of gas falling into the galaxy.
We use a scanning nanometer-scale superconducting quantum interference device to map the stray magnetic field produced by individual ferromagnetic nanotubes (FNTs) as a function of applied magnetic ...field. The images are taken as each FNT is led through magnetic reversal and are compared with micromagnetic simulations, which correspond to specific magnetization configurations. In magnetic fields applied perpendicular to the FNT long axis, their magnetization appears to reverse through vortex states, that is, configurations with vortex end domains or in the case of a sufficiently short FNT with a single global vortex. Geometrical imperfections in the samples and the resulting distortion of idealized magnetization configurations influence the measured stray-field patterns.
The medial temporal lobe memory system has long been identified as the brain region showing the first histopathological changes in early Alzheimer's disease (AD), and the functional decline observed ...in patients also points to a loss of function in this brain area. Nonetheless, the exact identity of the neurons and networks that undergo deterioration has not been determined so far. A recent study has identified the entorhinal and hippocampal neural circuits responsible for encoding new episodic memories. Using this novel model we describe the elements of the episodic memory network that are especially vulnerable in early AD. We provide a hypothesis of how reduced reelin signaling within such a network can promote AD-related changes. Establishing novel associations and creating a temporal structure for new episodic memories are both affected in AD. Here, we furnish a reasonable explanation for both of these previous observations.
Abstract
In antiferromagnetic spintronics, the read-out of the staggered magnetization or Néel vector is the key obstacle to harnessing the ultra-fast dynamics and stability of antiferromagnets for ...novel devices. Here, we demonstrate strong exchange coupling of Mn
2
Au, a unique metallic antiferromagnet that exhibits Néel spin-orbit torques, with thin ferromagnetic Permalloy layers. This allows us to benefit from the well-established read-out methods of ferromagnets, while the essential advantages of antiferromagnetic spintronics are only slightly diminished. We show one-to-one imprinting of the antiferromagnetic on the ferromagnetic domain pattern. Conversely, alignment of the Permalloy magnetization reorients the Mn
2
Au Néel vector, an effect, which can be restricted to large magnetic fields by tuning the ferromagnetic layer thickness. To understand the origin of the strong coupling, we carry out high resolution electron microscopy imaging and we find that our growth yields an interface with a well-defined morphology that leads to the strong exchange coupling.
Percolation theory dictates an intuitive picture depicting correlated regions in complex systems as densely connected clusters. While this picture might be adequate at small scales and apart from ...criticality, we show that highly correlated sites in complex systems can be inherently disconnected. This finding indicates a counter-intuitive organization of dynamical correlations, where functional similarity decouples from physical connectivity. We illustrate the phenomenon on the example of the disordered contact process (DCP) of infection spreading in heterogeneous systems. We apply numerical simulations and an asymptotically exact renormalization group technique (SDRG) in 1, 2 and 3 dimensional systems as well as in two-dimensional lattices with long-ranged interactions. We conclude that the critical dynamics is well captured by mostly one, highly correlated, but spatially disconnected cluster. Our findings indicate that at criticality the relevant, simultaneously infected sites typically do not directly interact with each other. Due to the similarity of the SDRG equations, our results hold also for the critical behavior of the disordered quantum Ising model, leading to quantum correlated, yet spatially disconnected, magnetic domains.
In many-body systems with quenched disorder, dynamical observables can be singular not only at the critical point, but in an extended region of the paramagnetic phase as well. These Griffiths ...singularities are due to rare regions, which are locally in the ordered phase and contribute to a large susceptibility. Here, we study the geometrical properties of rare regions in the transverse Ising model with dilution or with random couplings and transverse fields. In diluted models, the rare regions are percolation clusters, while in random models the ground state consists of a set of spin clusters, which are calculated by the strong disorder renormalization method. We consider the so called energy cluster, which has the smallest excitation energy and calculate its mass and linear extension in one-, two- and three-dimensions. Both average quantities are found to grow logarithmically with the linear size of the sample. Consequently, the energy clusters are not compact: for the diluted model they are isotropic and tree-like, while for the random model they are quasi-one-dimensional.
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