Non-perturbative theoretical description of two atoms in an optical lattice with time-dependent perturbations

A theoretical approach for a non-perturbative dynamical description of two interacting atoms in an optical lattice potential is introduced. The approach builds upon the stationary eigenstates found by a procedure described in Grishkevich et al. [Phys. Rev. A 84, 062710 (2011)]. It allows presently to treat any time-dependent external perturbation of the lattice potential up to quadratic order. Example calculations of the experimentally relevant cases of an acceleration of the lattice and the turning-on of an additional harmonic confinement are presented.Comment: 8 pages, 6 figure

Dicke quantum spin glass of atoms and photons

Recent studies of strongly interacting atoms and photons in optical cavities have rekindled interest in the Dicke model of atomic qubits coupled to discrete photon cavity modes. We study the multimode Dicke model with variable atom-photon couplings. We argue that a quantum spin glass phase can appear, with a random linear combination of the cavity modes superradiant. We compute atomic and photon spectral response functions across this quantum phase transition, both of which should be accessible in experiment.Comment: 4 pages, 3 figures, v2: described quantum optics set-up in more detail; extended discussion on photon correlation functions and experimental signatures; added reference

R-process Nucleosynthesis from Three-Dimensional Magnetorotational Core-Collapse Supernovae

We investigate r-process nucleosynthesis in three-dimensional (3D) general-relativistic magnetohydrodynamic simulations of rapidly rotating strongly magnetized core collapse. The simulations include a microphysical finite-temperature equation of state and a leakage scheme that captures the overall energetics and lepton number exchange due to postbounce neutrino emission and absorption. We track the composition of the ejected material using the nuclear reaction network SkyNet. Our results show that the 3D dynamics of magnetorotational core-collapse supernovae (CCSN) are important for their nucleosynthetic signature. We find that production of r-process material beyond the second peak is reduced by a factor of 100 when the magnetorotational jets produced by the rapidly rotating core undergo a kink instability. Our results indicate that 3D magnetorotationally powered CCSNe are a robust r-process source only if they are obtained by the collapse of cores with unrealistically large precollapse magnetic fields of order $10^{13}$G. Additionally, a comparison simulation that we restrict to axisymmetry, results in overly optimistic r-process production for lower magnetic field strengths.Comment: 10 pages, 9 figures, 2 tables. submitted to Ap

Silk nanoparticles : proof of lysosomotropic anticancer drug delivery at single cell resolution

Silk nanoparticles are expected to improve chemotherapeutic drug targeting to solid tumours by exploiting tumour pathophysiology, modifying the cellular pharmacokinetics of the payload and ultimately resulting in trafficking to lysosomes and triggering drug release. However, experimental proof for lysosomotropic drug delivery by silk nanoparticles in live cells is lacking and the importance of lysosomal pH and enzymes controlling drug release are currently unknown. Here, we demonstrate, in live single human breast cancer cells, the role of the lysosomal environment in determining silk nanoparticle-mediated drug release. MCF-7 human breast cancer cells endocytosed and trafficked drug-loaded native and PEGylated silk nanoparticles (approximately 100 nm in diameter) to lysosomes (n = 3), with subsequent drug release from the respective carriers and nuclear translocation within 5 h of dosing (n = 2). A combination of low pH and enzymatic degradation facilitated drug release from the silk nanoparticles (n = 3); perturbation of the acidic lysosomal pH and inhibition of serine, cysteine and threonine proteases resulted in a 42% ± 2.2% and 33% ± 3% reduction in nuclear-associated drug accumulation for native and PEGylated silk nanoparticles, respectively (n = 2). Overall, this study demonstrates the importance of lysosomal activity for anticancer drug release from silk nanoparticles, thereby providing direct evidence for lysosomotropic drug delivery in live cells

PEGylation-Dependent Metabolic Rewiring of Macrophages with Silk Fibroin Nanoparticles

Silk fibroin nanoparticles are emerging as promising nanomedicines, but their full therapeutic potential is yet to be realized. These nanoparticles can be readily PEGylated to improve colloidal stability and to tune degradation and drug release profiles; however, the relationship between silk fibroin nanoparticle PEGylation and macrophage activation still requires elucidation. Here, we used in vitro assays and nuclear magnetic resonance based metabolomics to examine the inflammatory phenotype and metabolic profiles of macrophages following their exposure to unmodified or PEGylated silk fibroin nanoparticles. The macrophages internalized both types of nanoparticles, but they showed different phenotypic and metabolic responses to each nanoparticle type. Unmodified silk fibroin nanoparticles induced the upregulation of several processes, including production of proinflammatory mediators (e.g., cytokines), release of nitric oxide, and promotion of antioxidant activity. These responses were accompanied by changes in the macrophage metabolomic profiles that were consistent with a proinflammatory state and that indicated an increase in glycolysis and reprogramming of the tricarboxylic acid cycle and the creatine kinase/phosphocreatine pathway. By contrast, PEGylated silk fibroin nanoparticles induced milder changes to both inflammatory and metabolic profiles, suggesting that immunomodulation of macrophages with silk fibroin nanoparticles is PEGylation-dependent. Overall, PEGylation of silk fibroin nanoparticles reduced the inflammatory and metabolic responses initiated by macrophages, and this observation could be used to guide the therapeutic applications of these nanoparticles. © 2019 American Chemical Society

Metabolic reprogramming of macrophages exposed to silk, poly(lactic-co-glycolic acid) and silica nanoparticles

Monitoring macrophage metabolism in response to nanoparticle exposure provides new insights into biological outcomes, such as inflammation or toxicity, and supports the design of tailored nanomedicines. We describe the metabolic signature of macrophages exposed to nanoparticles ranging in diameter from 100 to 125 nm and made from silk, poly(lactic-co-glycolic acid) or silica. Nanoparticles of this size and type are currently at various stages of pre-clinical and clinical development for drug delivery applications. We used 1H NMR analysis of cell extracts and culture media to quantify the changes in the intracellular and extracellular metabolomes of macrophages in response to nanoparticle exposure. Increased glycolytic activity, an altered tricarboxylic acid cycle and reduced ATP generation were consistent with a pro-inflammatory phenotype. Furthermore, amino acids possibly arising from autophagy, the creatine kinase/phosphocreatine system and a few osmolytes and antioxidants emerged as important players in the metabolic reprogramming of macrophages exposed to nanoparticles. This metabolic signature was a common response to all nanoparticles tested; however, the direction and magnitude of some variations were clearly nanoparticle specific, indicating material-induced biological specificity. Overall, metabolic reprogramming of macrophages can be achieved with nanoparticle treatments, modulated through the choice of the material, and monitored using 1H NMR metabolomics

Unraveling the Impact of High-Order Silk Structures on Molecular Drug Binding and Release Behaviors

Silk continues to amaze: over the past decade, new research threads have emerged that include the use of silk fibroin for advanced pharmaceutics, including its suitability for drug delivery. Despite this ongoing interest, the details of silk fibroin structures and their subsequent drug interactions at the molecular level remain elusive, primarily because of the difficulties encountered in modeling the silk fibroin molecule. Here, we generated an atomistic silk model containing amorphous and crystalline regions. We then exploited advanced well-tempered metadynamics simulations to generate molecular conformations that we subsequently exposed to classical molecular dynamics simulations to monitor both drug binding and release. Overall, this study demonstrated the importance of the silk fibroin primary sequence, electrostatic interactions, hydrogen bonding, and higher-order conformation in the processes of drug binding and release. © Copyright © 2019 American Chemical Society