WASH and Tsg101/ALIX-dependent diversion of stress-internalized EGFR from the canonical endocytic pathway

Stress exposure triggers ligand-independent EGF receptor (EGFR) endocytosis, but its post-endocytic fate and role in regulating signalling are unclear. We show that the p38 MAP kinase-dependent, EGFR tyrosine kinase (TK)-independent EGFR internalization induced by ultraviolet light C (UVC) or the cancer therapeutic cisplatin, is followed by diversion from the canonical endocytic pathway. Instead of lysosomal degradation or plasma membrane recycling, EGFR accumulates in a subset of LBPA-rich perinuclear multivesicular bodies (MVBs) distinct from those carrying EGF-stimulated EGFR. Stress-internalized EGFR co-segregates with exogenously expressed pre-melanosomal markers OA1 and fibrillar PMEL, following early endosomal sorting by the actin polymerization-promoting WASH complex. Stress-internalized EGFR is retained intracellularly by continued p38 activity in a mechanism involving ubiquitin-independent, ESCRT/ALIX-dependent incorporation onto intraluminal vesicles (ILVs) of MVBs. In contrast to the internalization-independent EGF-stimulated activation, UVC/cisplatin-triggered EGFR activation depends on EGFR internalization and intracellular retention. EGFR signalling from this MVB subpopulation delays apoptosis and might contribute to chemoresistance

Gravitational energy in a small region for the modified Einstein and Landau-Lifshitz pseudotensors

The purpose of the classical Einstein and Landau-Lifshitz pseudotensors is for determining the gravitational energy. Neither of them can guarantee a positive energy in holonomic frames. In the small sphere approximation, it has been required that the quasilocal expression for the gravitational energy-momentum density should be proportional to the Bel-Robinson tensor $B_{\alpha\beta\mu\nu}$. However, we propose a new tensor $V_{\alpha\beta\mu\nu}$ which is the sum of certain tensors $S_{\alpha\beta\mu\nu}$ and $K_{\alpha\beta\mu\nu}$, it has certain properties so that it gives the same gravitational "energy-momentum" content as $B_{\alpha\beta\mu\nu}$ does. Moreover, we show that a modified Einstein pseudotensor turns out to be one of the Chen-Nester quasilocal expressions, while the modified Landau-Lifshitz pseudotensor becomes the Papapetrou pseudotensor; these two modified pseudotensors have positive gravitational energy in a small region.Comment:

New positive small vacuum region gravitational energy expressions

We construct an infinite number of new holonomic quasi-local gravitational energy-momentum density pseudotensors with good limits asymptotically and in small regions, both materially and in vacuum. For small vacuum regions they are all a positive multiple of the Bel-Robinson tensor and consequently have positive energy.Comment: 4 page

Thermal stability and nitrogen redistribution in the〈Si〉/Ti/W–N/Al metallization scheme

Backscattering spectrometry, Auger electron spectroscopy, and x‐ray diffraction have been used to monitor the thin‐film reactions and nitrogen redistribution in the 〈Si〉/Ti/W–N/Al metallization system. It is found that nitrogen in the W–N layer redistributes into Ti after annealing at temperatures above 500 °C. As a consequence of this redistribution of nitrogen, a significant amount of interdiffusion between Al and the underlayers is observed after annealing at 550 °C. This result contrasts markedly with that for the 〈Si〉/W–N/Al system, where no interdiffusion can be detected after the same thermal treatment. We attribute this redistribution of nitrogen to the stronger affinity of Ti for nitrogen than W. If the Ti layer is replaced by a sputtered TiSi_(2.3) film, no redistribution of nitrogen or reactions can be detected after annealing at 550 °C for 30 min

The Rab-binding profiles of bacterial virulence factors during infection

Legionella pneumophila, the causative agent of Legionnaire's disease, uses its type IV secretion system to translocate over 300 effector proteins into host cells. These effectors subvert host cell signaling pathways to ensure bacterial proliferation. Despite their importance for pathogenesis, the roles of most of the effectors are yet to be characterized. Key to understanding the function of effectors is the identification of host proteins they bind during infection. We previously developed a novel tandem-affinity purification (TAP) approach using hexahistidine and BirA-specific biotinylation tags for isolating translocated effector complexes from infected cells whose composition were subsequently deciphered by mass spectrometry. Here we further advanced the workflow for the TAP approach and determined the infection-dependent interactomes of the effectors SidM and LidA, which were previously reported to promiscuously bind multiple Rab GTPases in vitro. In this study we defined a stringent subset of Rab GTPases targeted by SidM and LidA during infection, comprising of Rab1A, 1B, 6, and 10; in addition, LidA targets Rab14 and 18. Taken together, this study illustrates the power of this approach to profile the intracellular interactomes of bacterial effectors during infection

Neural Network Model for Apparent Deterministic Chaos in Spontaneously Bursting Hippocampal Slices

A neural network model that exhibits stochastic population bursting is studied by simulation. First return maps of inter-burst intervals exhibit recurrent unstable periodic orbit (UPO)-like trajectories similar to those found in experiments on hippocampal slices. Applications of various control methods and surrogate analysis for UPO-detection also yield results similar to those of experiments. Our results question the interpretation of the experimental data as evidence for deterministic chaos and suggest caution in the use of UPO-based methods for detecting determinism in time-series data.Comment: 4 pages, 5 .eps figures (included), requires psfrag.sty (included

Nonequilibrium-induced metal-superconductor quantum phase transition in graphene

We study the effects of dissipation and time-independent nonequilibrium drive on an open superconducting graphene. In particular, we investigate how dissipation and nonequilibrium effects modify the semi-metal-BCS quantum phase transition that occurs at half-filling in equilibrium graphene with attractive interactions. Our system consists of a graphene sheet sandwiched by two semi-infinite three-dimensional Fermi liquid reservoirs, which act both as a particle pump/sink and a source of decoherence. A steady-state charge current is established in the system by equilibrating the two reservoirs at different, but constant, chemical potentials. The nonequilibrium BCS superconductivity in graphene is formulated using the Keldysh path integral formalism, and we obtain generalized gap and number density equations valid for both zero and finite voltages. The behaviour of the gap is discussed as a function of both attractive interaction strength and electron densities for various graphene-reservoir couplings and voltages. We discuss how tracing out the dissipative environment (with or without voltage) leads to decoherence of Cooper pairs in the graphene sheet, hence to a general suppression of the gap order parameter at all densities. For weak enough attractive interactions we show that the gap vanishes even for electron densities away from half-filling, and illustrate the possibility of a dissipation-induced metal-superconductor quantum phase transition. We find that the application of small voltages does not alter the essential features of the gap as compared to the case when the system is subject to dissipation alone (i.e. zero voltage).Comment: 13 pages, 8 figure

On the energy of homogeneous cosmologies

An energy for the homogeneous cosmological models is presented. More specifically, using an appropriate natural prescription, we find the energy within any region with any gravitational source for a large class of gravity theories--namely those with a tetrad description--for all 9 Bianchi types. Our energy is given by the value of the Hamiltonian with homogeneous boundary conditions; this value vanishes for all regions in all Bianchi class A models, and it does not vanish for any class B model. This is so not only for Einstein's general relativity but, moreover, for the whole 3-parameter class of tetrad-teleparallel theories. For the physically favored one parameter subclass, which includes the teleparallel equivalent of Einstein's theory as an important special case, the energy for all class B models is, contrary to expectation, negative.Comment: 11 pages, reformated with minor change

Design and assembly sequence analysis of option 3 for CETF reference space station

A design and assembly sequence was conducted on one option of the Dual Keel Space Station examined by a NASA Critical Evaluation Task Force to establish viability of several variations of that option. A goal of the study was to produce and analyze technical data to support Task Force decisions to either examine particular Option 3 variations in more depth or eliminate them from further consideration. An analysis of the phasing assembly showed that use of an Expendable Launch Vehicle in conjunction with the Space Transportation System (STS) can accelerate the buildup of the Station and ease the STS launch rate constraints. The study also showed that use of an Orbital Maneuvering Vehicle on the first flight can significantly benefit Station assembly and, by performing Station subsystem functions, can alleviate the need for operational control and reboost systems during the early flights. In addition to launch and assembly sequencing, the study assessed stability and control, and analyzed node-packaging options and the effects of keel removal on the structural dynamics of the Station. Results of these analyses are presented and discussed