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The Space Weather Investigation Frontier (SWIFT) mission will aim at making major discoveries on the three-dimensional structure and dynamics of heliospheric structures that drive space weather. The focus will be on Interplanetary Coronal Mass Ejections (ICMEs) that originate from massive expulsions of plasma and magnetic flux from the solar corona. They cause the largest geomagnetic storms and solar energetic particle events, threatening to endanger life and disrupt technology on Earth and in space. A big current problem, both regarding fundamental solar-terrestrial physics and space weather, is that we do not yet understand spatial characteristics and temporal evolution of ICMEs and that the existing remote-sensing and in-situ observatories are not suited for resolving multi-layered and evolutionary structures in these massive storm drivers. Here, we propose a groundbreaking mission concept study using solar sail technology that, for the first time, will make continuous, in-situ multi-point observations along the Sun-Earth line beyond the Lagrange point L1 (sub-L1). This unique position, in combination with L1 assets, will allow distinguishing between local and global processes, spatial characteristics, temporal evolution, and particle energization mechanisms related to ICMEs. In addition, measurements of the magnetic field in earthbound ICMEs and their sub-structures from the SWIFT location will double the current forecasting lead-times from L1. This concept also paves the way for missions with increasingly longer forecasting lead-times, addressing NASA and NOAA’s space weather goals, as set forth by the Decadal Survey. The objective of this communication is to inform the community of the ongoing effort, including plans to further develop the mission concept, supported by the Heliophysics Flight Opportunities Studies (HFOS) program under NASA’s Research Opportunities in Space and Earth Sciences (ROSES).

Networks with higher order interactions, relevant to social groups, ecosystems and human brain, require new tools and instruments for their analysis. Gambuzza et al. propose an analytical approach which allows to find conditions for stable synchronization in many-body interaction networks.

We present a numerical study of dynamical correlations (structure factors) of the long-range generalization of the Fermi–Pasta–Ulam oscillator chain, where the strength of the interaction between two lattice sites decays as a power of the inverse of their distance. The structure factors at finite energy density display distinct peaks, corresponding to long-wavelength propagating modes, whose dispersion relation is compatible with the predictions of the linear theory. We demonstrate that dynamical scaling holds, with a dynamical exponent z that depends weakly on in the range . The lineshapes have a non-trivial functional form and appear somehow independent of . Within the accessible time and size ranges, we also find that the short-range limit is hardly attained even for relatively large values of . [ABSTRACT FROM AUTHOR]

Steady nonequilibrium states are investigated in a one-dimensional setup in the presence of two thermodynamic currents. Two paradigmatic nonlinear oscillators models are investigated: an XY chain and the discrete nonlinear Schrödinger equation. Their distinctive feature is that the relevant variable is an angle in both cases. We point out the importance of clearly distinguishing between energy and heat flux. In fact, even in the presence of a vanishing Seebeck coefficient, a coupling between (angular) momentum and energy arises, mediated by the unavoidable presence of a coherent energy flux. Such a contribution is the result of the ‘advection’ induced by the position-dependent angular velocity. As a result, in the XY model, the knowledge of the two diagonal elements of the Onsager matrix suffices to reconstruct its transport properties. The analysis of the nonequilibrium steady states finally allows to strengthen the connection between the two models. [ABSTRACT FROM AUTHOR]

The ambient solar wind that fills the heliosphere originates from multiple sources in the solar corona and is highly structured. It is often described as high-speed, relatively homogeneous, plasma streams from coronal holes and slow-speed, highly variable, streams whose source regions are under debate. A key goal of ESA/NASA's Solar Orbiter mission is to identify solar wind sources and understand what drives the complexity seen in the heliosphere. By combining magnetic field modelling and spectroscopic techniques with high-resolution observations and measurements, we show that the solar wind variability detected in situ by Solar Orbiter in March 2022 is driven by spatio-temporal changes in the magnetic connectivity to multiple sources in the solar atmosphere. The magnetic field footpoints connected to the spacecraft moved from the boundaries of a coronal hole to one active region (12961) and then across to another region (12957). This is reflected in the in situ measurements, which show the transition from fast to highly Alfvénic then to slow solar wind that is disrupted by the arrival of a coronal mass ejection. Our results describe solar wind variability at 0.5 au but are applicable to near-Earth observatories., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)

We study in detail a one-dimensional lattice model of a continuum, conserved field (mass) that is transferred deterministically between neighboring random sites. The model belongs to a wider class of lattice models capturing the joint effect of random advection and diffusion and encompassing as specific cases some models studied in the literature, such as those of Kang-Redner, Kipnis-Marchioro-Presutti, Takayasu-Taguchi, etc. The motivation for our setup comes from a straightforward interpretation of the advection of particles in one-dimensional turbulence, but it is also related to a problem of synchronization of dynamical systems driven by common noise. For finite lattices, we study both the coalescence of an initially spread field (interpreted as roughening), and the statistical steady-state properties. We distinguish two main size-dependent regimes, depending on the strength of the diffusion term and on the lattice size. Using numerical simulations and a mean-field approach, we study the statistics of the field. For weak diffusion, we unveil a characteristic hierarchical structure of the field. We also connect the model and the iterated function systems concept.

We perform a numerical study of transport properties of a one-dimensional chain with couplings decaying as an inverse power r^{-(1+σ)} of the intersite distance r and open boundary conditions, interacting with two heat reservoirs. Despite its simplicity, the model displays highly nontrivial features in the strong long-range regime -1<σ<0. At weak coupling with the reservoirs, the energy flux departs from the predictions of perturbative theory and displays anomalous superdiffusive scaling of the heat current with the chain size. We trace this behavior back to the transmission spectrum of the chain, which displays a self-similar structure with a characteristic σ-dependent fractal dimension.

Size dependence of energy transport and the effects of reduced dimensionality on transport coefficients are of key importance for understanding nonequilibrium properties of matter on the nanoscale. Here, we perform nonequilibrium and equilibrium simulations of heat conduction in a three-dimensional (3D) fluid with the multiparticle collision dynamics, interacting with two thermal walls. We find that the bulk 3D momentum-conserving fluid has a finite nondiverging thermal conductivity. However, for large aspect ratios of the simulation box, a crossover from 3D to one-dimensional (1D) abnormal behavior of the thermal conductivity occurs. In this case, we demonstrate a transition from normal to abnormal transport by a suitable decomposition of the energy current. These results not only provide a direct verification of Fourier's law, but also further confirm the validity of existing theories for 3D fluids. Moreover, they indicate that abnormal heat transport persists also for almost 1D fluids over a large range of sizes.

Various systems in physics, biology, social sciences and engineering have been successfully modeled as networks of coupled dynamical systems, where the links describe pairwise interactions. This is, however, too strong a limitation, as recent studies have revealed that higher-order many-body interactions are present in social groups, ecosystems and in the human brain, and they actually affect the emergent dynamics of all these systems. Here, we introduce a general framework to study coupled dynamical systems accounting for the precise microscopic structure of their interactions at any possible order. We show that complete synchronization exists as an invariant solution, and give the necessary condition for it to be observed as a stable state. Moreover, in some relevant instances, such a necessary condition takes the form of a Master Stability Function. This generalizes the existing results valid for pairwise interactions to the case of complex systems with the most general possible architecture.

Energy transport in one-dimensional chains of particles with three conservation laws is generically anomalous and belongs to the Kardar-Parisi-Zhang dynamical universality class. Surprisingly, some examples where an apparent normal heat diffusion is found over a large range of length scales were reported. We propose a novel physical explanation of these intriguing observations. We develop a scaling analysis that explains how this may happen in the vicinity of an integrable limit, such as, but not only, the famous Toda model. In this limit, heat transport is mostly supplied by quasiparticles with a very large mean free path ℓ. Upon increasing the system size L, three different regimes can be observed: a ballistic one, an intermediate diffusive range, and, eventually, the crossover to the anomalous (hydrodynamic) regime. Our theoretical considerations are supported by numerical simulations of a gas of diatomic hard-point particles for almost equal masses and of a weakly perturbed Toda chain. Finally, we discuss the case of the perturbed harmonic chain, which exhibits a yet different scenario.

Transport phenomena are ubiquitous in physics, and it is generally understood that the environmental disorder and noise deteriorates the transfer of excitations. There are, however, cases in which transport can be enhanced by fluctuations. In the present work, we show, by means of micromagnetics simulations, that transport efficiency in a chain of classical macrospins can be greatly increased by an optimal level of dephasing noise. We also demonstrate the same effect in a simplified model, the dissipative Discrete Nonlinear Schrödinger equation, subject to phase noise. Our results point towards the realization of a large class of magnonics and spintronics devices, where disorder and noise can be used to enhance spin-dependent transport efficiency.

We investigate thermal conduction in arrays of long-range interacting rotors and Fermi-Pasta-Ulam (FPU) oscillators coupled to two reservoirs at different temperatures. The strength of the interaction between two lattice sites decays as a power α of the inverse of their distance. We point out the necessity of distinguishing between energy flows towards or from the reservoirs and those within the system. We show that energy flow between the reservoirs occurs via a direct transfer induced by long-range couplings and a diffusive process through the chain. To this aim, we introduce a decomposition of the steady-state heat current that explicitly accounts for such direct transfer of energy between the reservoir. For 0≤α<1, the direct transfer term dominates, meaning that the system can be effectively described as a set of oscillators each interacting with the thermal baths. Also, the heat current exchanged with the reservoirs depends on the size of the thermalized regions: In the case in which such size is proportional to the system size N, the stationary current is independent on N. For α>1, heat transport mostly occurs through diffusion along the chain: For the rotors transport is normal, while for FPU the data are compatible with an anomalous diffusion, possibly with an α-dependent characteristic exponent.

Aldehyde oxidase (AOX) is a molibdo-flavoenzyme that has raised great interest in recent years, since its contribution in xenobiotic metabolism has not always been identified before clinical trials, with consequent negative effects on the fate of new potential drugs. The fundamental role of AOX in metabolizing xenobiotics is also due to the attempt of medicinal chemists to stabilize candidates toward cytochrome P450 activity, which increases the risk for new compounds to be susceptible to AOX nucleophile attack. Therefore, novel strategies to predict the potential liability of new entities toward the AOX enzyme are urgently needed to increase effectiveness, reduce costs, and prioritize experimental studies. In the present work, we present the most up-to-date computational method to predict liability toward human AOX (hAOX), for applications in drug design and pharmacokinetic optimization. The method was developed using a large data set of homogeneous experimental data, which is also disclosed as Supporting Information .

We study irreversible processes for nonlinear oscillators networks described by complex-valued Langevin equations that account for coupling to different thermochemical baths. Dissipation is introduced via non-Hermitian terms in the Hamiltonian of the model. We apply the stochastic thermodynamics formalism to compute explicit expressions for the entropy production rates. We discuss in particular the nonequilibrium steady states of the network characterized by a constant production rate of entropy and flows of energy and particle currents. For two specific examples, a one-dimensional chain and a dimer, numerical calculations are presented. The role of asymmetric coupling among the oscillators on the entropy production is illustrated.

Aldehyde oxidase (AOX) is a metabolic enzyme catalyzing the oxidation of aldehyde and aza-aromatic compounds and the hydrolysis of amides, moieties frequently shared by the majority of drugs. Despite its key role in human metabolism, to date only fragmentary information about the chemical features responsible for AOX susceptibility are reported and only "very local" structure-metabolism relationships based on a small number of similar compounds have been developed. This study reports a more comprehensive coverage of the chemical space of structures with a high risk of AOX phase I metabolism in humans. More than 270 compounds were studied to identify the site of metabolism and the metabolite(s). Both electronic [supported by density functional theory (DFT) calculations] and exposure effects were considered when rationalizing the structure-metabolism relationship., Competing Interests: The authors declare no conflict of interest.

By means of hybrid multiparticle collsion-particle-in-cell (MPC-PIC) simulations we study the dynamical scaling of energy and density correlations at equilibrium in moderately coupled two-dimensional (2D) and quasi-one-dimensional (1D) plasmas. We find that the predictions of nonlinear fluctuating hydrodynamics for the structure factors of density and energy fluctuations in 1D systems with three global conservation laws hold true also for 2D systems that are more extended along one of the two spatial dimensions. Moreover, from the analysis of the equilibrium energy correlators and density structure factors of both 1D and 2D neutral plasmas, we find that neglecting the contribution of the fluctuations of the vanishing self-consistent electrostatic fields overestimates the interval of frequencies over which the anomalous transport is observed. Such violations of the expected scaling in the currents correlation are found in different regimes, hindering the observation of the asymptotic scaling predicted by the theory.

Complex optical networks containing one or more gain sections are investigated, and the evidence of lasing action is reported; the emission spectrum reflects the topological disorder induced by the connections. A theoretical description compares well with the measurements, mapping the networks to directed graphs and showing the analogies with the problem of quantum chaos on graphs. We show that the interplay of chaotic diffusion and amplification leads to an emission statistic with characteristic heavy tails: for different topologies, an unprecedented experimental demonstration of Lévy statistics expected for random lasers is here provided for a continuous-wave pumped system. This result is also supported by a Monte Carlo simulation based on the ray random walk on the graph.

The NorA efflux pump is a potential drug target for reversal of resistance to selected antibacterial agents, and recently we described indole-based inhibitor candidates. Herein we report a second class of inhibitors derived from them but with significant differences in shape and size. In particular, compounds 13 and 14 are very potent inhibitors in that they demonstrated the lowest IC 50 values (2 μM) ever observed among all indole-based compounds we have evaluated.

Phenotypic screens, which focus on measuring and quantifying discrete cellular changes rather than affinity for individual recombinant proteins, have recently attracted renewed interest as an efficient strategy for drug discovery. In this article, we describe the discovery of a new chemical probe, bisamide (CCT251236), identified using an unbiased phenotypic screen to detect inhibitors of the HSF1 stress pathway. The chemical probe is orally bioavailable and displays efficacy in a human ovarian carcinoma xenograft model. By developing cell-based SAR and using chemical proteomics, we identified pirin as a high affinity molecular target, which was confirmed by SPR and crystallography.

Random lasers are optical sources where light is amplified by stimulated emission along random paths through an amplifying scattering medium. Connections between their physics and the one of quenched disordered nonlinear systems, notably spin glasses, have been recently suggested. Here we report a first experimental study of correlations of spectral fluctuations intensity in a random laser medium where the scatterers displacement significantly changes among consecutive shots. Remarkably, our results reveal that the replica symmetry breaking (RSB) phenomenology is robust with respect to an averaging over different realizations of the disorder. Moreover, besides opening new intriguing questions about the understanding of such a phenomenon, this work aims to clarify the connection between the RSB with the onset of the Lévy regime, i.e. the fluctuations regime that is a peculiar feature of the random lasing under critical conditions. Our results suggest that the former occurs independently of the latter and then the RSB phenomenology is a generic feature linked to the random laser threshold.

Bosentan, the first-in-class drug used in treatment of pulmonary arterial hypertension, is principally metabolized by the cytochromes P450, and it is responsible for cytochromes induction and drug-drug interaction events with moderate to severe consequences. A strategy to reduce drug-drug interactions consists of increasing the metabolic stability of the perpetrator, and fluorinated analogues are often designed to block the major sites of metabolism. In this paper bosentan analogues were synthesized, and their metabolism and biological activity were evaluated. All synthesized compounds showed an improved metabolic stability towards CYP2C9, with one maintaining a moderate antagonist effect towards the ETA receptor., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

The identification of antitumoral substances is the focus of intense biomedical research. Two structural analogues of thalidomide, LNO3 and L3, are two synthetic compounds that might possess such antitumor properties. We evaluated the toxicological effects of these substances, including cytotoxicity, genotoxicity and induction of apoptosis in HTC cells. Additionally, the production of free radicals (nitric oxide and superoxide) was investigated, and the expression of caspases genes 3, 8, and 9 were determined by RT-qPCR. The compounds exhibited cytotoxic effects that resulted in inhibited cell proliferation. LNO3 showed to be more effective and toxic than L3 in all assays. LNO3 stimulated the release of NO and superoxide, which was accompanied by the formation of peroxynitrite. Apoptosis was induced in a dose-dependent manner by both compounds; however, the expression of caspases 3, 8 and 9 was unchanged. These results suggested that L3 and LNO3 possess antiproliferative and pro-apoptotic effects in HTC cells. Additionally, although they exhibited cytotoxicity, L3 and LNO3 might be useful coadjuvants in tumor treatment studies.

Antibiotic resistance represents a worldwide concern, especially regarding the outbreak of methicillin-resistant Staphylococcus aureus, a common cause for serious skin and soft tissues infections. A major contributor to Staphylococcus aureus antibiotic resistance is the NorA efflux pump, which is able to extrude selected antibacterial drugs and biocides from the membrane, lowering their effective concentrations. Thus, the inhibition of NorA represents a promising and challenging strategy that would allow recycling of substrate antimicrobial agents. Among NorA inhibitors, the indole scaffold proved particularly effective and suitable for further optimization. In this study, some unexplored modifications on the indole scaffold are proposed. In particular, for the first time, substitutions at the C5 and N1 positions have been designed to give 48 compounds, which were synthesized and tested against norA-overexpressing S. aureus. Among them, 4 compounds have NorA IC50 values lower than 5.0 μM proving to be good efflux pump inhibitor (EPI) candidates. In addition, preliminary data on their ADME (absorption, distribution, metabolism, and excretion) profile is reported.

We study the anomalous dynamical scaling of equilibrium correlations in one-dimensional systems. Two different models are compared: the Fermi-Pasta-Ulam chain with cubic and quartic nonlinearity and a gas of point particles interacting stochastically through multiparticle collision dynamics. For both models-that admit three conservation laws-by means of detailed numerical simulations we verify the predictions of nonlinear fluctuating hydrodynamics for the structure factors of density and energy fluctuations at equilibrium. Despite this, violations of the expected scaling in the currents correlation are found in some regimes, hindering the observation of the asymptotic scaling predicted by the theory. In the case of the gas model this crossover is clearly demonstrated upon changing the coupling constant.

Bisphosphonates are the most important class of antiresorptive agents used against osteoclast-mediated bone loss, and, more recently, in oncology. These compounds have high affinity for calcium ions (Ca(2+)) and therefore target bone mineral, where they appear to be internalized selectively by bone-resorbing osteoclasts and inhibit osteoclast function. They are extensively used in healthcare, however they are affected by severe side effects; pharmacological properties of bisphosphonates depend on their molecular structure, which is frequently the cause of poor intestinal adsorption and low distribution. In this work we synthesized six novel bisphosphonate compounds having a variably substituted indole moiety to evaluate their extra- and intracellular calcium chelating ability in PE/CA-PJ15 cells. Preliminary in silico and in vitro ADME studies were also performed and the results suggested that the indole moiety plays an important role in cell permeability and metabolism properties., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

We investigate numerically the magnetization dynamics of an array of nanodisks interacting through the magnetodipolar coupling. In the presence of a temperature gradient, the chain reaches a nonequilibrium steady state where energy and magnetization currents propagate. This effect can be described as the flow of energy and particle currents in an off-equilibrium discrete nonlinear Schrödinger (DNLS) equation. This model makes transparent the transport properties of the system and allows for a precise definition of temperature and chemical potential for a precessing spin. The present study proposes a setup for the spin-Seebeck effect, and shows that its qualitative features can be captured by a general oscillator-chain model.

Long-range bonding interactions were evaluated using variable-temperature NMR spectroscopy and suitable 2'-CH2X-substituted phenylpyridines (X = Me, NMe2, OMe, F). It was found that the arylpyridyl rotational barriers were lower when electronegative atoms were bound to the α carbon of the 2' moiety. This effect was ascribed to a stabilizing interaction in the transition state due to the lone pair of the heterocyclic nitrogen with the α carbon. Computational support for this hypothesis came from CCSD(T)/6-31+G(d) calculations. Steric effects of the X moiety were ruled out by comparison of the rotational barriers of analogous biphenyls.

By means of a simple theoretical model and numerical simulations, we demonstrate the presence of persistent energy currents in a lattice of classical nonlinear oscillators with uniform temperature and chemical potential. In analogy with the well-known Josephson effect, the currents are proportional to the sine of the phase differences between the oscillators. Our results elucidate general aspects of nonequilibrium thermodynamics and point towards a way to practically control transport phenomena in a large class of systems. We apply the model to describe the phase-controlled spin-wave current in a bilayer nanopillar.

We study Anderson localization of the classical lattice waves in a chain with mass impurities distributed randomly through a power-law relation s-(1+α) with s as the distance between two successive impurities and α>0. This model of disorder is long-range correlated and is inspired by the peculiar structure of the complex optical systems known as Lévy glasses. Using theoretical arguments and numerics, we show that in the regime in which the average distance between impurities is finite with infinite variance, the small-frequency behavior of the localization length is ξ{ω)∼ω-α. The physical interpretation of this result is that, for small frequencies and long wavelengths, the waves feel an effective disorder whose fluctuations are scale dependent. Numerical simulations show that an initially localized wave-packet attains, at large times, a characteristic inverse power-law front with an α-dependent exponent which can be estimated analytically.

We study scattering of a periodic wave in a string on two lumped oscillators attached to it. The equations can be represented as a driven (by the incident wave) dissipative (due to radiation losses) system of delay differential equations of neutral type. Nonlinearity of oscillators makes the scattering non-reciprocal: The same wave is transmitted differently in two directions. Periodic regimes of scattering are analyzed approximately, using amplitude equation approach. We show that this setup can act as a nonreciprocal modulator via Hopf bifurcations of the steady solutions. Numerical simulations of the full system reveal nontrivial regimes of quasiperiodic and chaotic scattering. Moreover, a regime of a "chaotic diode," where transmission is periodic in one direction and chaotic in the opposite one, is reported.