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

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

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

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

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

Benchmark thermochemistry of the C_nH_{2n+2} alkane isomers (n=2--8) and performance of DFT and composite ab initio methods for dispersion-driven isomeric equilibria

The thermochemistry of linear and branched alkanes with up to eight carbons has been reexamined by means of W4, W3.2lite and W1h theories. `Quasi-W4' atomization energies have been obtained via isodesmic and hypohomodesmotic reactions. Our best atomization energies at 0 K (in kcal/mol) are: 1220.04 n-butane, 1497.01 n-pentane, 1774.15 n-hexane, 2051.17 n-heptane, 2328.30 n-octane, 1221.73 isobutane, 1498.27 isopentane, 1501.01 neopentane, 1775.22 isohexane, 1774.61 3-methylpentane, 1775.67 diisopropyl, 1777.27 neohexane, 2052.43 isoheptane, 2054.41 neoheptane, 2330.67 isooctane, and 2330.81 hexamethylethane. Our best estimates for $\Delta H^\circ_{f,298K}$ are: -30.00 n-butane, -34.84 n-pentane, -39.84 n-hexane, -44.74 n-heptane, -49.71 n-octane, -32.01 isobutane, -36.49 isopentane, -39.69 neopentane, -41.42 isohexane, -40.72 3-methylpentane, -42.08 diisopropyl, -43.77 neohexane, -46.43 isoheptane, -48.84 neoheptane, -53.29 isooctane, and -53.68 hexamethylethane. These are in excellent agreement (typically better than 1 kJ/mol) with the experimental heats of formation at 298 K obtained from the CCCBDB and/or NIST Chemistry WebBook databases. However, at 0 K a large discrepancy between theory and experiment (1.1 kcal/mol) is observed for only neopentane. This deviation is mainly due to the erroneous heat content function for neopentane used in calculating the 0 K CCCBDB value. The thermochemistry of these systems, especially of the larger alkanes, is an extremely difficult test for density functional methods. A posteriori corrections for dispersion are essential. Particularly for the atomization energies, the B2GP-PLYP and B2K-PLYP double-hybrids, and the PW6B95 hybrid-meta GGA clearly outperform other DFT functionals.Comment: (J. Phys. Chem. A, in press

Power plant maintenance scheduling using ant colony optimization: an improved formulation

Abstract It is common practice in the hydropower industry to either shorten the maintenance duration or to postpone maintenance tasks in a hydropower system when there is expected unserved energy based on current water storage levels and forecast storage inflows. It is therefore essential that a maintenance scheduling optimizer can incorporate the options of shortening the maintenance duration and/or deferring maintenance tasks in the search for practical maintenance schedules. In this article, an improved ant colony optimization-power plant maintenance scheduling optimization (ACO-PPMSO) formulation that considers such options in the optimization process is introduced. As a result, both the optimum commencement time and the optimum outage duration are determined for each of the maintenance tasks that need to be scheduled. In addition, a local search strategy is presented in this article to boost the robustness of the algorithm. When tested on a five-station hydropower system problem, the improved formulation is shown to be capable of allowing shortening of maintenance duration in the event of expected demand shortfalls. In addition, the new local search strategy is also shown to have significantly improved the optimization ability of the ACO-PPMSO algorithm

Growth inhibition of non-small cell lung cancer cells by AP-1 blockade using a cJun dominant-negative mutant

cJun, a major constituent of AP-1 transcription factor transducing multiple mitogen growth signals, is frequently overexpressed in non-small cell lung cancers (NSCLCs). The purpose of this study is to determine the effects of AP-1 blockade on the growth of NSCLC cells using a cJun dominant-negative mutant, TAM67. Transiently transfected TAM67 inhibited AP-1 transcriptional activity in NSCLC cell lines, NCI-H1299 (H1299), A549 and NCI-H520 (H520). The colony-forming efficiency of H1299 and A549 was reduced by TAM67, while that of H520 was not. To elucidate the effects of TAM67 on the growth of H1299, we established H1299 clone cells that expressed TAM67 under the control of a doxycycline-inducible promoter. In the H1299 clone cells, the induced TAM67 inhibited anchorage-dependent growth by promoting G1 cell-cycle block, but not by apoptosis. The induced TAM67 decreased the expression of a cell-cycle regulatory protein, cyclin A. TAM67 also inhibited anchorage-independent growth of these cells. Furthermore, TAM67 reduced growth of established xenograft tumours from these cells in nude mice. These results suggest that AP-1 plays an essential role in the growth of at least some of NSCLC cells

Simultaneous blockade of AP-1 and phosphatidylinositol 3-kinase pathway in non-small cell lung cancer cells

c-Jun is a major constituent of AP-1 transcription factor that transduces multiple mitogen growth signals, and it is frequently overexpressed in non-small cell lung cancers (NSCLCs). Earlier, we showed that blocking AP-1 by the overexpression of a c-Jun dominant-negative mutant, TAM67, inhibited NSCLC cell growth. The phosphatidylinositol 3-kinase (PI3K)/Akt signal transduction pathway is important in transformation, proliferation, survival and metastasis of NSCLC cells. In this study, we used NCI-H1299 Tet-on clone cells that express TAM67 under the control of inducible promoter to determine the effects of inhibition of AP-1 and PI3K on cell growth. The PI3K inhibitor, LY294002, produced a dose-dependent inhibition of growth in H1299 cells and that inhibition was enhanced by TAM67. TAM67 increased dephosphorylation of Akt induced by LY294002 and reduced the TPA response element DNA-binding of phosphorylated c-Jun. TAM67 increased G1 cell cycle blockade induced by LY294002, which was partially associated with cyclin A decrease and p27Kip1 accumulation. Furthermore, TAM67 and LY294002 act, at least additively, to inhibit anchorage-independent growth of the H1299 cells. These results suggest that AP-1 and PI3K/Akt pathways play an essential role in the growth of some NSCLC cells

The Cell Adhesion Molecule “CAR” and Sialic Acid on Human Erythrocytes Influence Adenovirus In Vivo Biodistribution

Although it has been known for 50 years that adenoviruses (Ads) interact with erythrocytes ex vivo, the molecular and structural basis for this interaction, which has been serendipitously exploited for diagnostic tests, is unknown. In this study, we characterized the interaction between erythrocytes and unrelated Ad serotypes, human 5 (HAd5) and 37 (HAd37), and canine 2 (CAV-2). While these serotypes agglutinate human erythrocytes, they use different receptors, have different tropisms and/or infect different species. Using molecular, biochemical, structural and transgenic animal-based analyses, we found that the primary erythrocyte interaction domain for HAd37 is its sialic acid binding site, while CAV-2 binding depends on at least three factors: electrostatic interactions, sialic acid binding and, unexpectedly, binding to the coxsackievirus and adenovirus receptor (CAR) on human erythrocytes. We show that the presence of CAR on erythrocytes leads to prolonged in vivo blood half-life and significantly reduced liver infection when a CAR-tropic Ad is injected intravenously. This study provides i) a molecular and structural rationale for Ad–erythrocyte interactions, ii) a basis to improve vector-mediated gene transfer and iii) a mechanism that may explain the biodistribution and pathogenic inconsistencies found between human and animal models