Scaling behavior of the dipole coupling energy in two-dimensional disordered magnetic nanostructures

Numerical calculations of the average dipole-coupling energy $\bar E_\mathrm{dip}$ in two-dimensional disordered magnetic nanostructures are performed as function of the particle coverage $C$. We observe that $\bar E_\mathrm{dip}$ scales as $\bar E_\mathrm{dip}\propto C^{\alpha^*}$ with an unusually small exponent $\alpha^*\simeq 0.8$--1.0 for coverages $C\lesssim20$. This behavior is shown to be primarly given by the contributions of particle pairs at short distances, which is intrinsically related to the presence of an appreciable degree of disorder. The value of $\alpha^*$ is found to be sensitive to the magnetic arrangement within the nanostructure and to the degree of disorder. For large coverages $C\gtrsim20$ we obtain $\bar E_\mathrm{dip}\propto C^\alpha$ with $\alpha=3/2$, in agreement with the straighforward scaling of the dipole coupling as in a periodic particle setup. Taking into account the effect of single-particle anisotropies, we show that the scaling exponent can be used as a criterion to distinguish between weakly interacting ($\alpha^* \simeq 1.0$) and strongly interacting ($\alpha^* \simeq 0.8$) particle ensembles as function of coverage.Comment: accepted for publication in Phys.Rev.

Screening of classical Casimir forces by electrolytes in semi-infinite geometries

We study the electrostatic Casimir effect and related phenomena in equilibrium statistical mechanics of classical (non-quantum) charged fluids. The prototype model consists of two identical dielectric slabs in empty space (the pure Casimir effect) or in the presence of an electrolyte between the slabs. In the latter case, it is generally believed that the long-ranged Casimir force due to thermal fluctuations in the slabs is screened by the electrolyte into some residual short-ranged force. The screening mechanism is based on a "separation hypothesis": thermal fluctuations of the electrostatic field in the slabs can be treated separately from the pure image effects of the "inert" slabs on the electrolyte particles. In this paper, by using a phenomenological approach under certain conditions, the separation hypothesis is shown to be valid. The phenomenology is tested on a microscopic model in which the conducting slabs and the electrolyte are modelled by the symmetric Coulomb gases of point-like charges with different particle fugacities. The model is solved in the high-temperature Debye-H\"uckel limit (in two and three dimensions) and at the free fermion point of the Thirring representation of the two-dimensional Coulomb gas. The Debye-H\"uckel theory of a Coulomb gas between dielectric walls is also solved.Comment: 25 pages, 2 figure

Exact exchange-correlation potential of a ionic Hubbard model with a free surface

We use Lanczos exact diagonalization to compute the exact exchange-correlation (xc) potential of a Hubbard chain with large binding energy ("the bulk") followed by a chain with zero binding energy ("the vacuum"). Several results of density functional theory in the continuum (sometimes controversial) are verified in the lattice. In particular we show explicitly that the fundamental gap is given by the gap in the Kohn-Sham spectrum plus a contribution due to the jump of the xc-potential when a particle is added. The presence of a staggered potential and a nearest-neighbor interaction V allows to simulate a ionic solid. We show that in the ionic regime in the small hopping amplitude limit the xc-contribution to the gap equals V, while in the Mott regime it is determined by the Hubbard U interaction. In addition we show that correlations generates a new potential barrier at the surface

Phase Coexistence of a Stockmayer Fluid in an Applied Field

We examine two aspects of Stockmayer fluids which consists of point dipoles that additionally interact via an attractive Lennard-Jones potential. We perform Monte Carlo simulations to examine the effect of an applied field on the liquid-gas phase coexistence and show that a magnetic fluid phase does exist in the absence of an applied field. As part of the search for the magnetic fluid phase, we perform Gibbs ensemble simulations to determine phase coexistence curves at large dipole moments, $\mu$. The critical temperature is found to depend linearly on $\mu^2$ for intermediate values of $\mu$ beyond the initial nonlinear behavior near $\mu=0$ and less than the $\mu$ where no liquid-gas phase coexistence has been found. For phase coexistence in an applied field, the critical temperatures as a function of the applied field for two different $\mu$ are mapped onto a single curve. The critical densities hardly change as a function of applied field. We also verify that in an applied field the liquid droplets within the two phase coexistence region become elongated in the direction of the field.Comment: 23 pages, ReVTeX, 7 figure

Production of CXC and CC chemokines by human antigen-presenting cells in response to Lassa virus or closely related immunogenic viruses, and in cynomolgus monkeys with lassa fever.

International audienceThe pathogenesis of Lassa fever (LF), a hemorrhagic fever endemic to West Africa, remains unclear. We previously compared Lassa virus (LASV) with its genetically close, but nonpathogenic homolog Mopeia virus (MOPV) and demonstrated that the strong activation of antigen-presenting cells (APC), including type I IFN production, observed in response to MOPV probably plays a crucial role in controlling infection. We show here that human macrophages (MP) produce large amounts of CC and CXC chemokines in response to MOPV infection, whereas dendritic cells (DC) release only moderate amounts of CXC chemokines. However, in the presence of autologous T cells, DCs produced CC and CXC chemokines. Chemokines were produced in response to type I IFN synthesis, as the levels of both mediators were strongly correlated and the neutralization of type I IFN resulted in an inhibition of chemokine production. By contrast, LASV induced only low levels of CXCL-10 and CXCL-11 production. These differences in chemokine production may profoundly affect the generation of virus-specific T-cell responses and may therefore contribute to the difference of pathogenicity between these two viruses. In addition, a recombinant LASV (rLASV) harboring the NP-D389A/G392A mutations, which abolish the inhibition of type I IFN response by nucleoprotein (NP), induced the massive synthesis of CC and CXC chemokines in both DC and MP, confirming the crucial role of arenavirus NP in immunosuppression and pathogenicity. Finally, we confirmed, using PBMC samples and lymph nodes obtained from LASV-infected cynomolgus monkeys, that LF was associated with high levels of CXC chemokine mRNA synthesis, suggesting that the very early synthesis of these mediators may be correlated with a favourable outcome

A cell-based chemical-genetic screen for amino acid stress response inhibitors reveals torins reverse stress kinase GCN2 signaling

mTORC1 and GCN2 are serine/threonine kinases that control how cells adapt to amino acid availability. mTORC1 responds to amino acids to promote translation and cell growth while GCN2 senses limiting amino acids to hinder translation via eIF2α phosphorylation. GCN2 is an appealing target for cancer therapies because malignant cells can harness the GCN2 pathway to temper the rate of translation during rapid amino acid consumption. To isolate new GCN2 inhibitors, we created cell-based, amino acid limitation reporters via genetic manipulation of Ddit3 (encoding the transcription factor CHOP). CHOP is strongly induced by limiting amino acids and in this context, GCN2-dependent. Using leucine starvation as a model for essential amino acid sensing, we unexpectedly discovered ATP-competitive PI3 kinase-related kinase inhibitors, including ATR and mTOR inhibitors like torins, completely reversed GCN2 activation in a time-dependent way. Mechanistically, via inhibiting mTORC1-dependent translation, torins increased intracellular leucine, which was sufficient to reverse GCN2 activation and the downstream integrated stress response including stress-induced transcriptional factor ATF4 expression. Strikingly, we found that general translation inhibitors mirrored the effects of torins. Therefore, we propose that mTOR kinase inhibitors concurrently inhibit different branches of amino acid sensing by a dual mechanism involving direct inhibition of mTOR and indirect suppression of GCN2 that are connected by effects on the translation machinery. Collectively, our results highlight distinct ways of regulating GCN2 activity

Neuroblastoma Formation Requires Unconventional CD4 T Cells and Arginase-1-Dependent Myeloid Cells

Immune cells regulate tumor growth by mirroring their function as tissue repair organizers in normal tissues. To understand the different facets of immune-tumor collaboration through genetics, spatial transcriptomics, and immunologic manipulation with noninvasive, longitudinal imaging, we generated a penetrant double oncogene-driven autochthonous model of neuroblastoma. Spatial transcriptomic analysis showed that CD4(+) and myeloid populations colocalized within the tumor parenchyma, while CD8(+) T cells and B cells were peripherally dispersed. Depletion of CD4(+) T cells or CCR2(+) macrophages, but not B cells, CD8(+) T cells, or natural killer (NK) cells, prevented tumor formation. Tumor CD4(+) T cells displayed unconventional phenotypes and were clonotypically diverse and antigen independent. Within the myeloid fraction, tumor growth required myeloid cells expressing arginase-1. Overall, these results demonstrate how arginine-metabolizing myeloid cells conspire with pathogenic CD4(+) T cells to create permissive conditions for tumor formation, suggesting that these protumorigenic pathways could be disabled by targeting myeloid arginine metabolism. Significance: A new model of human neuroblastoma provides ways to track tumor formation and expansion in living animals, allowing identification of CD4(+) T-cell and macrophage functions required for oncogenesis. [GRAPHICS

Environmental arginine controls multinuclear giant cell metabolism and formation

Multinucleated giant cells (MGCs) are implicated in many diseases including schistosomiasis, sarcoidosis and arthritis. MGC generation is energy intensive to enforce membrane fusion and cytoplasmic expansion. Using receptor activator of nuclear factor kappa-Beta ligand (RANKL) induced osteoclastogenesis to model MGC formation, here we report RANKL cellular programming requires extracellular arginine. Systemic arginine restriction improves outcome in multiple murine arthritis models and its removal induces preosteoclast metabolic quiescence, associated with impaired tricarboxylic acid (TCA) cycle function and metabolite induction. Effects of arginine deprivation on osteoclastogenesis are independent of mTORC1 activity or global transcriptional and translational inhibition. Arginine scarcity also dampens generation of IL-4 induced MGCs. Strikingly, in extracellular arginine absence, both cell types display flexibility as their formation can be restored with select arginine precursors. These data establish how environmental amino acids control the metabolic fate of polykaryons and suggest metabolic ways to manipulate MGC-associated pathologies and bone remodelling. Multinucleated giant cells (MGCs) are important in the pathogenesis of various diseases. Here, the authors demonstrate that extracellular presence of the amino acid arginine is required for MGC formation and metabolism, suggesting a translational impact for strategies utilizing systemic arginine depletion in MGC-mediated diseases

Full-sky Models of Galactic Microwave Emission and Polarization at Subarcminute Scales for the Python Sky Model

Polarized foreground emission from the Galaxy is one of the biggest challenges facing current and upcoming cosmic microwave background (CMB) polarization experiments. We develop new models of polarized Galactic dust and synchrotron emission at CMB frequencies that draw on the latest observational constraints; that employ the “polarization fraction tensor” framework to couple intensity and polarization in a physically motivated way; and that allow for stochastic realizations of small-scale structure at subarcminute angular scales currently unconstrained by full-sky data. We implement these models into the publicly available Python Sky Model (PySM) software and additionally provide PySM interfaces to select models of dust and CO emission from the literature. We characterize the behavior of each model by quantitatively comparing it to observational constraints in both maps and power spectra, demonstrating an overall improvement over previous PySM models. Finally, we synthesize models of the various Galactic foreground components into a coherent suite of three plausible microwave skies that span a range of astrophysical complexity allowed by current data. Author contributions to this paper can be found at the end of this work

Spike-Timing Precision and Neuronal Synchrony Are Enhanced by an Interaction between Synaptic Inhibition and Membrane Oscillations in the Amygdala

The basolateral complex of the amygdala (BLA) is a critical component of the neural circuit regulating fear learning. During fear learning and recall, the amygdala and other brain regions, including the hippocampus and prefrontal cortex, exhibit phase-locked oscillations in the high delta/low theta frequency band (∼2–6 Hz) that have been shown to contribute to the learning process. Network oscillations are commonly generated by inhibitory synaptic input that coordinates action potentials in groups of neurons. In the rat BLA, principal neurons spontaneously receive synchronized, inhibitory input in the form of compound, rhythmic, inhibitory postsynaptic potentials (IPSPs), likely originating from burst-firing parvalbumin interneurons. Here we investigated the role of compound IPSPs in the rat and rhesus macaque BLA in regulating action potential synchrony and spike-timing precision. Furthermore, because principal neurons exhibit intrinsic oscillatory properties and resonance between 4 and 5 Hz, in the same frequency band observed during fear, we investigated whether compound IPSPs and intrinsic oscillations interact to promote rhythmic activity in the BLA at this frequency. Using whole-cell patch clamp in brain slices, we demonstrate that compound IPSPs, which occur spontaneously and are synchronized across principal neurons in both the rat and primate BLA, significantly improve spike-timing precision in BLA principal neurons for a window of ∼300 ms following each IPSP. We also show that compound IPSPs coordinate the firing of pairs of BLA principal neurons, and significantly improve spike synchrony for a window of ∼130 ms. Compound IPSPs enhance a 5 Hz calcium-dependent membrane potential oscillation (MPO) in these neurons, likely contributing to the improvement in spike-timing precision and synchronization of spiking. Activation of the cAMP-PKA signaling cascade enhanced the MPO, and inhibition of this cascade blocked the MPO. We discuss these results in the context of spike-timing dependent plasticity and modulation by neurotransmitters important for fear learning, such as dopamine