Multi-layered control of Galectin-8 mediated autophagy during adenovirus cell entry through a conserved PPxY motif in the viral capsid.

Cells employ active measures to restrict infection by pathogens, even prior to responses from the innate and humoral immune defenses. In this context selective autophagy is activated upon pathogen induced membrane rupture to sequester and deliver membrane fragments and their pathogen contents for lysosomal degradation. Adenoviruses, which breach the endosome upon entry, escape this fate by penetrating into the cytosol prior to autophagosome sequestration of the ruptured endosome. We show that virus induced membrane damage is recognized through Galectin-8 and sequesters the autophagy receptors NDP52 and p62. We further show that a conserved PPxY motif in the viral membrane lytic protein VI is critical for efficient viral evasion of autophagic sequestration after endosomal lysis. Comparing the wildtype with a PPxY-mutant virus we show that depletion of Galectin-8 or suppression of autophagy in ATG5-/- MEFs rescues infectivity of the PPxY-mutant virus while depletion of the autophagy receptors NDP52, p62 has only minor effects. Furthermore we show that wildtype viruses exploit the autophagic machinery for efficient nuclear genome delivery and control autophagosome formation via the cellular ubiquitin ligase Nedd4.2 resulting in reduced antigenic presentation. Our data thus demonstrate that a short PPxY-peptide motif in the adenoviral capsid permits multi-layered viral control of autophagic processes during entry

Spin states of zigzag-edged Mobius graphene nanoribbons from first principles

Mobius graphene nanoribbons have only one edge topologically. How the magnetic structures, previously associated with the two edges of zigzag-edged flat nanoribbons or cyclic nanorings, would change for their Mobius counterparts is an intriguing question. Using spin-polarized density functional theory, we shed light on this question. We examine spin states of zigzag-edged Mobius graphene nanoribbons (ZMGNRs) with different widths and lengths. We find a triplet ground state for a Mobius cyclacene, while the corresponding two-edged cyclacene has an open-shell singlet ground state. For wider ZMGNRs, the total magnetization of the ground state is found to increase with the ribbon length. For example, a quintet ground state is found for a ZMGNR. Local magnetic moments on the edge carbon atoms form domains of majority and minor spins along the edge. Spins at the domain boundaries are found to be frustrated. Our findings show that the Mobius topology (i.e., only one edge) causes ZMGNRs to favor one spin over the other, leading to a ground state with non-zero total magnetization.Comment: 17 pages, 4 figure

Models of organometallic complexes for optoelectronic applications

Organometallic complexes have potential applications as the optically active components of organic light emitting diodes (OLEDs) and organic photovoltaics (OPV). Development of more effective complexes may be aided by understanding their excited state properties. Here we discuss two key theoretical approaches to investigate these complexes: first principles atomistic models and effective Hamiltonian models. We review applications of these methods, such as, determining the nature of the emitting state, predicting the fraction of injected charges that form triplet excitations, and explaining the sensitivity of device performance to small changes in the molecular structure of the organometallic complexes.Comment: To appear in themed issue of J. Mat. Chem. on the modelling of material

Orthogonal methods based ant colony search for solving continuous optimization problems

Research into ant colony algorithms for solving continuous optimization problems forms one of the most significant and promising areas in swarm computation. Although traditional ant algorithms are designed for combinatorial optimization, they have shown great potential in solving a wide range of optimization problems, including continuous optimization. Aimed at solving continuous problems effectively, this paper develops a novel ant algorithm termed "continuous orthogonal ant colony" (COAC), whose pheromone deposit mechanisms would enable ants to search for solutions collaboratively and effectively. By using the orthogonal design method, ants in the feasible domain can explore their chosen regions rapidly and e±ciently. By implementing an "adaptive regional radius" method, the proposed algorithm can reduce the probability of being trapped in local optima and therefore enhance the global search capability and accuracy. An elitist strategy is also employed to reserve the most valuable points. The performance of the COAC is compared with two other ant algorithms for continuous optimization of API and CACO by testing seventeen functions in the continuous domain. The results demonstrate that the proposed COAC algorithm outperforms the others

A design programme for dilute phase pneumatic conveyors

Thesis (MScEng (Mechanical and Mechatronic Engineering))--University of Stellenbosch, 1997.A computer programme for the simulation of dilute phase pneumatic conveying of solids is presented. This includes positive pressure and vacuum pneumatic conveying. The characteristic conveying parameters such as the conveying absolute pressure, conveying air density, interstitial and average air velocity, particle velocity and voidage are calculated by integrating five differential equations that govern two-phase flow. The two-phase flow is approximated as one-dimensional along the pipe axis. Density and acceleration effects are accounted for. The integration is carried out by means of the Runge-Kutta-Fehlberg method yielding conveying parameter traces along the length ofthe pipeline. A new method is presented for the determination of the solids friction coefficient from the solids motion equation. This allows for a more accurate determination of the solids velocity in the pipeline when compared to currently used methods. The computer model results are compared to experimental results for cement and ice conveying yielding good correlation for the main output parameters. The theory for the scaling and calculation of Roots blower performance characteristics is presented. This is implemented in a Roots blower selection programme as an integral part of determining the prime air mover for the design of a pneumatic conveyor. The aim of providing a fast, user-friendly interface in terms of pipeline geometry input, simulation and data visualisation has been achieved by using the advantages of object orientated programming and the visual user interface of the DELPHI programming language

A Halomethane thermochemical network from iPEPICO experiments and quantum chemical calculations

Internal energy selected halomethane cations CH3Cl+, CH2Cl2+, CHCl3+, CH3F+, CH2F2+, CHClF2+ and CBrClF2+ were prepared by vacuum ultraviolet photoionization, and their lowest energy dissociation channel studied using imaging photoelectron photoion coincidence spectroscopy (iPEPICO). This channel involves hydrogen atom loss for CH3F+, CH2F2+ and CH3Cl+, chlorine atom loss for CH2Cl2+, CHCl3+ and CHClF2+, and bromine atom loss for CBrClF2+. Accurate 0 K appearance energies, in conjunction with ab initio isodesmic and halogen exchange reaction energies, establish a thermochemical network, which is optimized to update and confirm the enthalpies of formation of the sample molecules and their dissociative photoionization products. The ground electronic states of CHCl3+, CHClF2+ and CBrClF2+ do not confirm to the deep well assumption, and the experimental breakdown curve deviates from the deep well model at low energies. Breakdown curve analysis of such shallow well systems supplies a satisfactorily succinct route to the adiabatic ionization energy of the parent molecule, particularly if the threshold photoelectron spectrum is not resolved and a purely computational route is unfeasible. The ionization energies have been found to be 11.47 ± 0.01 eV, 12.30 ± 0.02 eV and 11.23 ± 0.03 eV for CHCl3, CHClF2 and CBrClF2, respectively. The updated 0 K enthalpies of formation, ∆fHo0K(g) for the ions CH2F+, CHF2+, CHCl2+, CCl3+, CCl2F+ and CClF2+ have been derived to be 844.4 ± 2.1, 601.6 ± 2.7, 890.3 ± 2.2, 849.8 ± 3.2, 701.2 ± 3.3 and 552.2 ± 3.4 kJ mol–1, respectively. The ∆fHo0K(g) values for the neutrals CCl4, CBrClF2, CClF3, CCl2F2 and CCl3F and have been determined to be –94.0 ± 3.2, –446.6 ± 2.7, –702.1 ± 3.5, –487.8 ± 3.4 and –285.2 ± 3.2 kJ mol–1, respectively

Hanford waste tank safety issues

This paper presents an overview of the potential high-activity waste safety issues in the 177 underground radioactive waste storage tanks at the Hanford Site. Also, included is a discussion of the strategy and plans to remedy hazardous conditions and remove other deficiencies related to the operation of the tanks. A three-pronged multimillion dollar integrated program has been initiated that (1) assesses and, on an as needed basis, defines remediation and/or mitigation actions to allow interim stabilization of high risk waste tanks; (2) upgrades existing facilities and instrumentation to meet current nuclear facility operations standards; and (3) addresses and upgrades the conduct of operations. For tanks that are considered at risk, extensive management controls presently are employed to ensure that the tanks continue to be maintained in a safe manner. In addition, comprehensive monitoring, characterization and applied research, and engineering efforts have been initiated to support resolution of safety issues. A key element of the Westinghouse Hanford Company effort is preventing future problems associated with creating potentially incompatible wastes as part of waste management activities associated with the planned disposal of the wastes in these storage tanks. Such efforts also will provide the basis for safe near future remediation of tanks and define and maintain the envelope of safety to support the ultimate disposal of all high- activity waste in Hanford Site tanks. 6 refs., 1 fig., 1 tab

Uniform electron gases

We show that the traditional concept of the uniform electron gas (UEG) --- a homogeneous system of finite density, consisting of an infinite number of electrons in an infinite volume --- is inadequate to model the UEGs that arise in finite systems. We argue that, in general, a UEG is characterized by at least two parameters, \textit{viz.} the usual one-electron density parameter $\rho$ and a new two-electron parameter $\eta$. We outline a systematic strategy to determine a new density functional $E(\rho,\eta)$ across the spectrum of possible $\rho$ and $\eta$ values.Comment: 8 pages, 2 figures, 5 table

Identification of the Rem-responsive element of mouse mammary tumor virus

Mouse mammary tumor virus (MMTV) has previously been shown to encode a functional homolog of the human immunodeficiency virus-1 (HIV-1) nuclear export protein Rev, termed Rem. Here, we show that deletion of the rem gene from a MMTV molecular clone interfered with the nucleo-cytoplasmic transport of genomic length viral mRNA and resulted in a loss of viral capsid (Gag) protein production. Interestingly, nuclear export of single-spliced env mRNA was only moderately affected, suggesting that this transcript is, at least to some extent, transported via a distinct, Rem-independent export mechanism. To identify and characterize a cis-acting RNA element required for Rem responsiveness (RmRE), extensive computational and functional analyses were performed. By these means a region of 490 nt corresponding to positions nt 8517–nt 9006 in the MMTV reference strain was identified as RmRE. Deletion of this fragment, which spans the env-U3 junction region, abolished Gag expression. Furthermore, insertion of this sequence into a heterologous HIV-1-based reporter construct restored, in the presence of Rem, HIV-1 Gag expression to levels determined for the Rev/RRE export system. These results clearly demonstrate that the identified region, whose geometry resembles that of other retroviral-responsive elements, is capable to functionally substitute, in the presence of Rem, for Rev/RRE and thus provide unequivocal evidence that MMTV is a complex retrovirus