We present the main results from the second model intercomparison within the GEWEX (Global Energy and Water cycle EXperiment) Atmospheric Boundary Layer Study (GABLS). The target is to examine the ...diurnal cycle over land in today’s numerical weather prediction and climate models for operational and research purposes. The set-up of the case is based on observations taken during the Cooperative Atmosphere-Surface Exchange Study-1999 (CASES-99), which was held in Kansas, USA in the early autumn with a strong diurnal cycle with no clouds present. The models are forced with a constant geostrophic wind, prescribed surface temperature and large-scale divergence. Results from 30 different model simulations and one large-eddy simulation (LES) are analyzed and compared with observations. Even though the surface temperature is prescribed, the models give variable near-surface air temperatures. This, in turn, gives rise to differences in low-level stability affecting the turbulence and the turbulent heat fluxes. The increase in modelled upward sensible heat flux during the morning transition is typically too weak and the growth of the convective boundary layer before noon is too slow. This is related to weak modelled near-surface winds during the morning hours. The agreement between the models, the LES and observations is the best during the late afternoon. From this intercomparison study, we find that modelling the diurnal cycle is still a big challenge. For the convective part of the diurnal cycle, some of the first-order schemes perform somewhat better while the turbulent kinetic energy (TKE) schemes tend to be slightly better during nighttime conditions. Finer vertical resolution tends to improve results to some extent, but is certainly not the solution to all the deficiencies identified.
Degradation of connexins and gap junctions Falk, Matthias M.; Kells, Rachael M.; Berthoud, Viviana M.
FEBS letters,
April 17, 2014, Letnik:
588, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Connexin proteins are short-lived within the cell, whether present in the secretory pathway or in gap junction plaques. Their levels can be modulated by their rate of degradation. Connexins, at ...different stages of assembly, are degraded through the proteasomal, endo-/lysosomal, and phago-/lysosomal pathways. In this review, we summarize the current knowledge about connexin and gap junction degradation including the signals and protein–protein interactions that participate in their targeting for degradation.
Proteins fated to be internalized by clathrin-mediated endocytosis require an endocytic motif, where AP-2 or another adaptor protein can bind and recruit clathrin. Tyrosine and di-leucine-based ...sorting signals are such canonical motifs. Connexin 43 (Cx43) has three canonical tyrosine-based endocytic motifs, two of which have been previously shown to recruit clathrin and mediate its endocytosis. In addition, di-leucine-based motifs have been characterized in the Cx32 C-terminal domain and shown to mediate its endocytosis. Here, we examined the amino acid sequences of all 21 human connexins to identify endocytic motifs across the connexin gene family. We find that although there is limited conservation of endocytic motifs between connexins, 14 of the 21 human connexins contain one or more canonical tyrosine or di-leucine-based endocytic motif in their C-terminal or intracellular loop domain. Three connexins contain non-canonical (modified) di-leucine motifs. However, four connexins (Cx25, Cx26, Cx31, and Cx40.1) do not harbor any recognizable endocytic motif. Interestingly, live cell time-lapse imaging of different GFP-tagged connexins that either contain or do not contain recognizable endocytic motifs readily undergo endocytosis, forming clearly identifiable annular gap junctions when expressed in HeLa cells. How connexins without defined endocytic motifs are endocytosed is currently not known. Our results demonstrate that an array of endocytic motifs exists in the connexin gene family. Further analysis will establish whether the sites we identified in this in silico analysis are legitimate endocytic motifs.
Gap junctions (GJs) exhibit a complex modus of assembly and degradation to maintain balanced intercellular communication (GJIC). Several growth factors, including vascular endothelial growth factor ...(VEGF), have been reported to disrupt cell-cell junctions and abolish GJIC. VEGF directly stimulates VEGF-receptor tyrosine kinases on endothelial cell surfaces. Exposing primary porcine pulmonary artery endothelial cells (PAECs) to VEGF for 15 min resulted in a rapid and almost complete loss of connexin43 (Cx43) GJs at cell-cell appositions and a concomitant increase in cytoplasmic, vesicular Cx43. After prolonged incubation periods (60 min), Cx43 GJs reformed and intracellular Cx43 were restored to levels observed before treatment. GJ internalization correlated with efficient inhibition of GJIC, up to 2.8-fold increased phosphorylation of Cx43 serine residues 255, 262, 279/282, and 368, and appeared to be clathrin driven. Phosphorylation of serines 255, 262, and 279/282 was mediated by MAPK, whereas serine 368 phosphorylation was mediated by PKC. Pharmacological inhibition of both signaling pathways significantly reduced Cx43 phosphorylation and GJ internalization. Together, our results indicate that growth factors such as VEGF activate a hierarchical kinase program--including PKC and MAPK--that induces GJ internalization via phosphorylation of well-known regulatory amino acid residues located in the Cx43 C-terminal tail.
Anomalous thermal diffusivity in underdoped YBa₂Cu₃O6+x Zhang, Jiecheng; Levenson-Falk, Eli M.; Ramshaw, B. J. ...
Proceedings of the National Academy of Sciences - PNAS,
05/2017, Letnik:
114, Številka:
21
Journal Article
Recenzirano
Odprti dostop
The thermal diffusivity in the ab plane of underdoped YBCO crystals is measured by means of a local optical technique in the temperature range of 25–300 K. The phase delay between a point heat source ...and a set of detection points around it allows for high-resolution measurement of the thermal diffusivity and its in-plane anisotropy. Although the magnitude of the diffusivity may suggest that it originates from phonons, its anisotropy is comparable with reported values of the electrical resistivity anisotropy. Furthermore, the anisotropy drops sharply below the charge order transition, again similar to the electrical resistivity anisotropy. Both of these observations suggest that the thermal diffusivity has pronounced electronic as well as phononic character. At the same time, the small electrical and thermal conductivities at high temperatures imply that neither well-defined electron nor phonon quasiparticles are present in this material. We interpret our results through a strongly interacting incoherent electron–phonon “soup” picture characterized by a diffusion constant
D
~
v
B
2
τ
, where vB
is the soup velocity, and scattering of both electrons and phonons saturates a quantum thermal relaxation time τ ∼ ħ/kBT.
We consider mixed-integer optimal control problems, whose optimality conditions involve global combinatorial optimization aspects for the corresponding Hamiltonian pointwise in time. We propose a ...time-domain decomposition, which makes this problem class accessible for mixed-integer programming using parallel-in-time direct discretizations. The approach is based on a decomposition of the optimality system and the interpretation of the resulting subproblems as suitably chosen mixed-integer optimal control problems on subintervals in time. An iterative procedure then ensures continuity of the states at the boundaries of the subintervals via co-state information encoded in virtual controls. We prove convergence of this iterative scheme for discrete-continuous linear-quadratic problems and present numerical results both for linear-quadratic as well as nonlinear problems.
We consider integer-restricted optimal control of systems governed by abstract semilinear evolution equations. This includes the problem of optimal control design for certain distributed parameter ...systems endowed with multiple actuators, where the task is to minimize costs associated with the dynamics of the system by choosing, for each instant in time, one of the actuators together with ordinary controls. We consider relaxation techniques that are already used successfully for mixed-integer optimal control of ordinary differential equations. Our analysis yields sufficient conditions such that the optimal value and the optimal state of the relaxed problem can be approximated with arbitrary precision by a control satisfying the integer restrictions. The results are obtained by semigroup theory methods. The approach is constructive and gives rise to a numerical method. We supplement the analysis with numerical experiments.
Abstract
We study with a 3D particle-in-cell simulation discontinuities between an electron–positron pair plasma and magnetized electrons and protons. A pair plasma is injected at one simulation ...boundary with a speed 0.6
c
along its normal. It expands into an electron-proton plasma and a magnetic field that points orthogonally to the injection direction. Diamagnetic currents expel the magnetic field from within the pair plasma and pile it up in front of it. It pushes electrons, which induces an electric field pulse ahead of the magnetic one. This initial electromagnetic pulse (EMP) confines the pair plasma magnetically and accelerates protons electrically. The fast flow of the injected pair plasma across the protons behind the initial EMP triggers the filamentation instability. Some electrons and positrons cross the injection boundary and build up a second EMP. Electron-cyclotron drift instabilities perturb the plasma ahead of both EMPs seeding a Rayleigh–Taylor (RT)-type instability. Despite equally strong perturbations ahead of both EMPs, the second EMP is much more stable than the initial one. We attribute the rapid collapse of the initial EMP to the filamentation instability, which perturbed the plasma behind it. The RT-type instability transforms the planar EMPs into transition layers, in which magnetic flux ropes and electrostatic forces due to uneven numbers of electrons and positrons slow down and compress the pair plasma and accelerate protons. In our simulation, the expansion speed of the pair cloud decreased by about an order of magnitude and its density increased by the same factor. Its small thickness implies that it is capable of separating a relativistic pair outflow from an electron-proton plasma, which is essential for collimating relativistic jets of pair plasma in collisionless astrophysical plasma.
Gap junctions (GJs) are the only known cellular structures that allow a direct transfer of signaling molecules from cell-to-cell by forming hydrophilic channels that bridge the opposing membranes of ...neighboring cells. The crucial role of GJ-mediated intercellular communication (GJIC) for coordination of development, tissue function, and cell homeostasis is now well documented. In addition, recent findings have fueled the novel concepts that connexins, although redundant, have unique and specific functions, that GJIC may play a significant role in unstable, transient cell–cell contacts, and that GJ hemi-channels by themselves may function in intra-/extracellular signaling. Assembly of these channels is a complicated, highly regulated process that includes biosynthesis of the connexin subunit proteins on endoplasmic reticulum membranes, oligomerization of compatible subunits into hexameric hemi-channels (connexons), delivery of the connexons to the plasma membrane, head-on docking of compatible connexons in the extracellular space at distinct locations, arrangement of channels into dynamic, spatially and temporally organized GJ channel aggregates (so-called plaques), and coordinated removal of channels into the cytoplasm followed by their degradation. Here we review the current knowledge of the processes that lead to GJ biosynthesis and degradation, draw comparisons to other membrane proteins, highlight novel findings, point out contradictory observations, and provide some provocative suggestive solutions.
Structural properties of molecules are of primary concern in many fields. This report provides a comprehensive overview on techniques that have been developed in the fields of molecular graphics and ...visualization with a focus on applications in structural biology. The field heavily relies on computerized geometric and visual representations of three‐dimensional, complex, large and time‐varying molecular structures. The report presents a taxonomy that demonstrates which areas of molecular visualization have already been extensively investigated and where the field is currently heading. It discusses visualizations for molecular structures, strategies for efficient display regarding image quality and frame rate, covers different aspects of level of detail and reviews visualizations illustrating the dynamic aspects of molecular simulation data. The survey concludes with an outlook on promising and important research topics to foster further success in the development of tools that help to reveal molecular secrets.
Structural properties of molecules are of primary concern in many fields. This report provides a comprehensive overview on techniques that have been developed in the fields of molecular graphics and visualization with a focus on applications in structural biology. The field heavily relies on computerized geometric and visual representations of three‐dimensional, complex, large and time‐varying molecular structures. The report presents a taxonomy that demonstrates which areas of molecular visualization have already been extensively investigated and where the field is currently heading. It discusses visualizations for molecular structures, strategies for efficient display regarding image quality and frame rate, covers different aspects of level of detail and reviews visualizations illustrating the dynamic aspects of molecular simulation data.
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