Simulation of laminar to transitional wakes past cylinders with a discontinuous Galerkin inviscid shallow water model

Laminar to transitional wakes occur in slow, quasi-steady flows past cylinders at low cylinder Reynolds numbers (R ed ≤ 250). Inviscid numerical solvers of the depth-averaged shallow water equations (SWE) introduce numerical dissipation that, depending on Red, may imitate the mechanisms of viscous turbulent models. However, the numerical dissipation rate in a second-order finite volume (FV2) SWE solver is so large at a practical resolution that this can instead hide these mechanisms. The extra numerical complexity of the second-order discontinuous Galerkin (DG2) SWE solver results in a lower dissipation rate, making it a potential alternative to the FV2 solver to reproduce cylinder wakes. This paper compares the DG2 and FV2 solvers, initially for wake formation behind one cylinder. The findings confirm that DG2 can reproduce the expected wake formations, which FV2 fails to capture, even at a 10-fold finer resolution. It is further demonstrated that DG2 is capable of reproducing key features of the flow fields observed in a laboratory random cylinder array

Targeted CRISPR activation and knockout screenings identify novel doxorubicin transporters

PurposeTissue-specific drug uptake has not been well studied, compared to the deeper understanding of drug resistance mediated by the cellular efflux system such as MDR1 proteins. It has been suggested that many drugs need active or defined transporters to pass the cell membrane. In contrast to efflux components induced after anti-cancer drugs reach the intracellular compartment, drug importers are required for initial drug responses. Furthermore, tissue-specific uptake of anti-cancer drugs may directly impact the side effects of many drugs when they accumulate in healthy tissues. Therefore, linking anti-cancer drugs to their respective drug import transporters would directly help to predict drug responses, whilst minimizing side effects.MethodsTo identify drug transporters of the commonly used anti-cancer drug doxorubicin, we performed focused CRISPR activation and knockout genetic screens targeting all potential membrane-associated transporters and proteins. We monitored the direct uptake of doxorubicin by fluorescence-activated cell sorting (FACS) as the screening readout for identifying transporters/proteins directly involved in doxorubicin uptake.ResultsIntegrating the data from these comprehensive CRISPR screenings, we confirmed previously indicated doxorubicin exporters such as ABCB1 and ABCG2 genes, and identified novel doxorubicin importer gene SLC2A3 (GLUT3). Upregulation of SLC2A3 led to higher doxorubicin uptake and better cell killing, indicating SLC2A3 could be a new marker to predict doxorubicin drug response and minimize side effects for the personalized application of this conventional chemotherapeutic drug.ConclusionsOur study provides a comprehensive way for identifying drug transporters, as exemplified by the commonly used anti-cancer drug doxorubicin. The newly identified importers may have direct clinical implications for the personalized application of doxorubicin in treating distinct tumors. Our results also highlight the necessity of combining both CRISPR knockout and CRISPR activation genetic screens to identify drug transporters.Chemical Immunolog

Quantization of adiabatic pumped charge in the presence of superconducting lead

We investigate the parametric electron pumping of a double barrier structure in the presence of a superconducting lead. The parametric pumping is facilitated by cyclic variation of the barrier heights $x_1$ and $x_2$ of the barriers. In the weak coupling regime, there exists a resonance line in the parameter space $(x_1,x_2)$ so that the energy of the quasi-bound state is in line with the incoming Fermi energy. Levinson et al found recently that the pumped charge for each pumping cycle is quantized with $Q=2e$ for normal structure when the pumping contour encircles the resonance line. In the presence of a superconducting lead, we find that the pumped charge is quantized with the value $2e$

Characterization of submicron particles influenced by mixed biogenic and anthropogenic emissions using high-resolution aerosol mass spectrometry: Results from CARES

An Aerodyne high resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) was deployed during the Carbonaceous Aerosols and Radiative Effects Study (CARES) that took place in northern California in June 2010. We present results obtained at Cool (denoted as the T1 site of the project) in the foothills of the Sierra Nevada Mountains, where intense biogenic emissions are periodically mixed with urban outflow transported by daytime southwesterly winds from the Sacramento metropolitan area. During this study, the average mass loading of submicrometer particles (PM1) was 3.0 μg m−3, dominated by organics (80%) and sulfate (9.9%). The organic aerosol (OA) had a nominal formula of C1H1.38N0.004OM0.44, thus an average organic mass-to-carbon (OM/OC) ratio of 1.70. Two distinct oxygenated OA factors were identified via Positive matrix factorization (PMF) of the high-resolution mass spectra of organics. The more oxidized MO-OOA (O/C = 0.54) was interpreted as a surrogate for secondary OA (SOA) influenced by biogenic emissions whereas the less oxidized LO-OOA (O/C = 0.42) was found to represent SOA formed in photochemically processed urban emissions. LO-OOA correlated strongly with ozone and MO-OOA correlated well with two 1st generation isoprene oxidation products (methacrolein and methyl vinyl ketone), indicating that both SOAs were relatively fresh. A hydrocarbon like OA (HOA) factor was also identified, representing primary emissions mainly due to local traffic. On average, SOA (= MO-OOA + LO-OOA) accounted for 91% of the total OA mass and 72% of the PM1 mass observed at Cool. Twenty three periods of urban plumes from T0 (Sacramento) to T1 (Cool) were identified using the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem). The average PM1 mass loading was considerably higher in urban plumes than in air masses dominated by biogenic SOA. The change in OA mass relative to CO (ΔOA/ΔCO) varied in the range of 5-196 μg m−3 ppm−1, reflecting large variability in SOA production. The highest ΔOA/ΔCO was reached when air masses were dominated by anthropogenic emissions in the presence of a high concentration of biogenic volatile organic compounds (BVOCs). This ratio, which was 97 μg m−3 ppm−1 on average, was much higher than when urban plumes arrived in a low BVOC environment (~36 μg m−3 ppm−1) or during other periods dominated by biogenic SOA (35 μg m−3 ppm−1). These results demonstrate that SOA formation is enhanced when anthropogenic emissions interact with biogenic precursors

Thermodynamics of Dipolar Chain Systems

The thermodynamics of a quantum system of layers containing perpendicularly oriented dipolar molecules is studied within an oscillator approximation for both bosonic and fermionic species. The system is assumed to be built from chains with one molecule in each layer. We consider the effects of the intralayer repulsion and quantum statistical requirements in systems with more than one chain. Specifically, we consider the case of two chains and solve the problem analytically within the harmonic Hamiltonian approach which is accurate for large dipole moments. The case of three chains is calculated numerically. Our findings indicate that thermodynamic observables, such as the heat capacity, can be used to probe the signatures of the intralayer interaction between chains. This should be relevant for near future experiments on polar molecules with strong dipole moments.Comment: 15 pages, 5 figures, final versio

A Helicity-Based Method to Infer the CME Magnetic Field Magnitude in Sun and Geospace: Generalization and Extension to Sun-Like and M-Dwarf Stars and Implications for Exoplanet Habitability

Patsourakos et al. (Astrophys. J. 817, 14, 2016) and Patsourakos and Georgoulis (Astron. Astrophys. 595, A121, 2016) introduced a method to infer the axial magnetic field in flux-rope coronal mass ejections (CMEs) in the solar corona and farther away in the interplanetary medium. The method, based on the conservation principle of magnetic helicity, uses the relative magnetic helicity of the solar source region as input estimates, along with the radius and length of the corresponding CME flux rope. The method was initially applied to cylindrical force-free flux ropes, with encouraging results. We hereby extend our framework along two distinct lines. First, we generalize our formalism to several possible flux-rope configurations (linear and nonlinear force-free, non-force-free, spheromak, and torus) to investigate the dependence of the resulting CME axial magnetic field on input parameters and the employed flux-rope configuration. Second, we generalize our framework to both Sun-like and active M-dwarf stars hosting superflares. In a qualitative sense, we find that Earth may not experience severe atmosphere-eroding magnetospheric compression even for eruptive solar superflares with energies ~ 10^4 times higher than those of the largest Geostationary Operational Environmental Satellite (GOES) X-class flares currently observed. In addition, the two recently discovered exoplanets with the highest Earth-similarity index, Kepler 438b and Proxima b, seem to lie in the prohibitive zone of atmospheric erosion due to interplanetary CMEs (ICMEs), except when they possess planetary magnetic fields that are much higher than that of Earth.Comment: http://adsabs.harvard.edu/abs/2017SoPh..292...89

Insights into the function of silver as an oxidation catalyst by ab initio, atomistic thermodynamics

To help understand the high activity of silver as an oxidation catalyst, e.g., for the oxidation of ethylene to epoxide and the dehydrogenation of methanol to formaldehyde, the interaction and stability of oxygen species at the Ag(111) surface has been studied for a wide range of coverages. Through calculation of the free energy, as obtained from density-functional theory and taking into account the temperature and pressure via the oxygen chemical potential, we obtain the phase diagram of O/Ag(111). Our results reveal that a thin surface-oxide structure is most stable for the temperature and pressure range of ethylene epoxidation and we propose it (and possibly other similar structures) contains the species actuating the catalysis. For higher temperatures, low coverages of chemisorbed oxygen are most stable, which could also play a role in oxidation reactions. For temperatures greater than about 775 K there are no stable oxygen species, except for the possibility of O atoms adsorbed at under-coordinated surface sites Our calculations rule out thicker oxide-like structures, as well as bulk dissolved oxygen and molecular ozone-like species, as playing a role in the oxidation reactions.Comment: 15 pages including 9 figures, Related publications can be found at http://www.fhi-berlin.mpg.de/th/paper.htm

Relation Between Chiral Susceptibility and Solutions of Gap Equation in Nambu--Jona-Lasinio Model

We study the solutions of the gap equation, the thermodynamic potential and the chiral susceptibility in and beyond the chiral limit at finite chemical potential in the Nambu--Jona-Lasinio (NJL) model. We give an explicit relation between the chiral susceptibility and the thermodynamic potential in the NJL model. We find that the chiral susceptibility is a quantity being able to represent the furcation of the solutions of the gap equation and the concavo-convexity of the thermodynamic potential in NJL model. It indicates that the chiral susceptibility can identify the stable state and the possibility of the chiral phase transition in NJL model.Comment: 21 pages, 6 figures, misprints are correcte

Basal Mitophagy Occurs Independently of PINK1 in Mouse Tissues of High Metabolic Demand

Dysregulated mitophagy has been linked to Parkinson’s disease (PD) due to the role of PTEN-induced kinase 1 (PINK1) in mediating depolarization-induced mitophagy in vitro. Elegant mouse reporters have revealed the pervasive nature of basal mitophagy in vivo, yet the role of PINK1 and tissue metabolic context remains unknown. Using mito-QC, we investigated the contribution of PINK1 to mitophagy in metabolically active tissues. We observed a high degree of mitophagy in neural cells, including PDrelevant mesencephalic dopaminergic neurons and microglia. In all tissues apart from pancreatic islets, loss of Pink1 did not influence basal mitophagy, despite disrupting depolarization-induced Parkin activation. Our findings provide the first in vivo evidence that PINK1 is detectable at basal levels and that basal mammalian mitophagy occurs independently of PINK1. This suggests multiple, yet-tobe- discovered pathways orchestrating mammalian mitochondrial integrity in a context-dependent fashion, and this has profound implications for our molecular understanding of vertebrate mitophagy

Electric current circuits in astrophysics

Cosmic magnetic structures have in common that they are anchored in a dynamo, that an external driver converts kinetic energy into internal magnetic energy, that this magnetic energy is transported as Poynting fl ux across the magnetically dominated structure, and that the magnetic energy is released in the form of particle acceleration, heating, bulk motion, MHD waves, and radiation. The investigation of the electric current system is particularly illuminating as to the course of events and the physics involved. We demonstrate this for the radio pulsar wind, the solar flare, and terrestrial magnetic storms