Integration of a virus membrane protein into the lipid bilayer of target cells as a prerequisite for immune cytolysis

Structural requirements for membrane antigens on target cells to mediate immune cytolysis were studied in a model system with purified membrane proteins from Semliki Forest virus (SFV). These SFV spike proteins were isolated in the form of detergent- and lipid-free protein micelles (29S complexes) or, after reconstitution into lipid vesicles, in the form of virosomes. Both the 29S complexes and the virosomes were found to bind well to murine tumor cells (P815 or Eb). When these cells, however, were used as target cells in complement-dependent lysis or in antibody-dependent cell- mediated cytotoxicity assays in the presence of anti-SFV serum, they were not lysed, although they effectively bound the antibody and consumed complement. The same tumor cells infected with SFV served as positive controls in both assays. Different results were obtained when inactivated Sendai virus was added as a fusion reagent to the cells coated with either virosomes or 29S complexes. Under these conditions the virosome-coated cells became susceptible to SFV- specific lysis, whereas the 29S complex-coated cells remained resistant. Evidence that the susceptibility to lysis ofvirosome-coated cells was dependent on active fusion and, therefore, integration of the viral antigens into the lipid bilayer of the target cells was derived from control experiments with enzyme-treated Sendai virus preparations. The 29S complexes and the virosomes partially and selectively blocked the target cell lysis by anti-H-2 sera but not by anti-non-H-2 sera confirming our previous finding that major histocompatibility antigens serve as receptors for SFV. The general significance of these findings for mechanisms of immune cytolysis is dicussed

Coupled dynamics of RNA folding and nanopore translocation

The translocation of structured RNA or DNA molecules through narrow pores necessitates the opening of all base pairs. Here, we study the interplay between the dynamics of translocation and base-pairing theoretically, using kinetic Monte Carlo simulations and analytical methods. We find that the transient formation of basepairs that do not occur in the ground state can significantly speed up translocation.Comment: 4 pages, 3 figures, to appear in Physical Review Letter

A review of modular strategies and architecture within manufacturing operations

This paper reviews existing modularity and modularization literature within manufacturing operations. Its purpose is to examine the tools, techniques, and concepts relating to modular production, to draw together key issues currently dominating the literature, to assess managerial implications associated with the emerging modular paradigm, and to present an agenda for future research directions. The review is based on journal papers included in the ABI/Inform electronic database and other noteworthy research published as part of significant research programmes. The research methodology concerns reviewing existing literature to identify key modular concepts, to determine modular developments, and to present a review of significant contributions to the field. The findings indicate that the modular paradigm is being adopted in a number of manufacturing organizations. As a result a range of conceptual tools, techniques, and frameworks has emerged and the field of modular enquiry is in the process of codifying the modular lexicon and developing appropriate modular strategies commensurate with the needs of manufacturers. Modular strategies and modular architecture were identified as two key issues currently dominating the modular landscape. Based on this review, the present authors suggest that future research areas need to focus on the development and subsequent standardization of interface protocols, cross-brand module use, supply chain power, transparency, and trust. This is the first review of the modular landscape and as such provides insights into, first, the development of modularization and, second, issues relating to designing modular products and modular supply chains

Crystal growth in fused solvent systems

The successful nucleation of bismuth germanate, B12GeO20 on a high quality seed and the growth of regions of single crystals of the same orientation of the seed are reported. Lead germanate, Pb5Ge3O11 was also identified as a ferroelectric crystal with large electrooptic and nonlinear optic constants. Solvent criteria, solvent/development, and crystal growth are discussed, and recommendations for future studies are included

Phonon anomalies in pure and underdoped R{1-x}K{x}Fe{2}As{2} (R = Ba, Sr) investigated by Raman light scattering

We present a detailed temperature dependent Raman light scattering study of optical phonons in Ba{1-x}K{x}Fe{2}As{2} (x ~ 0.28, superconducting Tc ~ 29 K), Sr{1-x}K{x}Fe{2}As{2} (x ~ 0.15, Tc ~ 29 K) and non-superconducting BaFe{2}As{2} single crystals. In all samples we observe a strong continuous narrowing of the Raman-active Fe and As vibrations upon cooling below the spin-density-wave transition Ts. We attribute this effect to the opening of the spin-density-wave gap. The electron-phonon linewidths inferred from these data greatly exceed the predictions of ab-initio density functional calculations without spin polarization, which may imply that local magnetic moments survive well above Ts. A first-order structural transition accompanying the spin-density-wave transition induces discontinuous jumps in the phonon frequencies. These anomalies are increasingly suppressed for higher potassium concentrations. We also observe subtle phonon anomalies at the superconducting transition temperature Tc, with a behavior qualitatively similar to that in the cuprate superconductors.Comment: 5 pages, 6 figures, accepted versio

Dynamics of protein-protein encounter: a Langevin equation approach with reaction patches

We study the formation of protein-protein encounter complexes with a Langevin equation approach that considers direct, steric and thermal forces. As three model systems with distinctly different properties we consider the pairs barnase:barstar, cytochrome c:cytochrome c peroxidase and p53:MDM2. In each case, proteins are modeled either as spherical particles, as dipolar spheres or as collection of several small beads with one dipole. Spherical reaction patches are placed on the model proteins according to the known experimental structures of the protein complexes. In the computer simulations, concentration is varied by changing box size. Encounter is defined as overlap of the reaction patches and the corresponding first passage times are recorded together with the number of unsuccessful contacts before encounter. We find that encounter frequency scales linearly with protein concentration, thus proving that our microscopic model results in a well-defined macroscopic encounter rate. The number of unsuccessful contacts before encounter decreases with increasing encounter rate and ranges from 20-9000. For all three models, encounter rates are obtained within one order of magnitude of the experimentally measured association rates. Electrostatic steering enhances association up to 50-fold. If diffusional encounter is dominant (p53:MDM2) or similarly important as electrostatic steering (barnase:barstar), then encounter rate decreases with decreasing patch radius. More detailed modeling of protein shapes decreases encounter rates by 5-95 percent. Our study shows how generic principles of protein-protein association are modulated by molecular features of the systems under consideration. Moreover it allows us to assess different coarse-graining strategies for the future modelling of the dynamics of large protein complexes

Open Space – a collaborative process for facilitating Tourism IT partnerships

The success of IT projects depends on the success of the partnerships on which they are based. However past research by the author has identified a significant rate of failure in these partnerships, predominantly due to an overly technical mindset, leading to the question: “how do we ensure that, as technological solutions are implemented within tourism, due consideration is given to human-centred issues?” The tourism partnership literature is explored for additional insights revealing that issues connected with power, participation and normative positions play a major role. The method, Open Space, is investigated for its ability to engage stakeholders in free and open debate. This paper reports on a one-day Open Space event sponsored by two major intermediaries in the UK travel industry who wanted to consult their business partners. Both the running of the event and its results reveal how Open Space has the potential to address some of the weaknesses associated with tourism partnerships

Lepton Pair Čerenkov Radiation Emitted by Tachyonic Neutrinos: Lorentz-Covariant Approach and IceCube Data

Current experiments do not exclude the possibility that one or more neutrinos are very slightly superluminal or that they have a very small tachyonic mass. Important bounds on the size of a hypothetical tachyonic neutrino mass term are set by lepton pair Čerenkov radiation (LPCR), that is, by the decay channel → e+ e- , which proceeds via a virtual Z0 boson. Here, we use a Lorentz-invariant dispersion relation which leads to very tight constraints on the tachyonic mass of neutrinos; we also calculate decay and energy loss rates. A possible cutoff seen in the IceCube neutrino spectrum for Ev \u3e 2 PeV, due to the potential onset of LPCR, is discussed

Two-Loop Bethe Logarithms for non-S Levels

Two-loop Bethe logarithms are calculated for excited P and D states in hydrogenlike systems, and estimates are presented for all states with higher angular momenta. These results complete our knowledge of the P and D energy levels in hydrogen at the order of alpha^8 m_e c^2, where m_e is the electron mass and c is the speed of light, and scale as Z^6, where Z is the nuclear charge number. Our analytic and numerical calculations are consistent with the complete absence of logarithmic terms of order (alpha/pi)^2 (Z alpha)^6 ln[(Z alpha)^(-2)] m_e c^2 for D states and all states with higher angular momenta. For higher excited P and D states, a number of poles from lower-lying levels have to subtracted in the numerical evaluation. We find that, surprisingly, the corrections of the "squared decay-rate type" are the numerically dominant contributions in the order (alpha/pi)^2 (Z alpha)^6 m_e c^2 for states with large angular momenta, and provide an estimate of the entire B_60-coefficient for Rydberg states with high angular momentum quantum numbers. Our results reach the predictive limits of the quantum electrodynamic theory of the Lamb shift.Comment: 14 pages, RevTe