Structural basis of complement membrane attack complex formation

In response to complement activation, the membrane attack complex (MAC) assembles from fluid-phase proteins to form pores in lipid bilayers. MAC directly lyses pathogens by a ‘multi-hit’ mechanism; however, sublytic MAC pores on host cells activate signalling pathways. Previous studies have described the structures of individual MAC components and subcomplexes; however, the molecular details of its assembly and mechanism of action remain unresolved. Here we report the electron cryo-microscopy structure of human MAC at subnanometre resolution. Structural analyses define the stoichiometry of the complete pore and identify a network of interaction interfaces that determine its assembly mechanism. MAC adopts a ‘split-washer’ configuration, in contrast to the predicted closed ring observed for perforin and cholesterol-dependent cytolysins. Assembly precursors partially penetrate the lipid bilayer, resulting in an irregular β-barrel pore. Our results demonstrate how differences in symmetric and asymmetric components of the MAC underpin a molecular basis for pore formation and suggest a mechanism of action that extends beyond membrane penetration

A projective Dirac operator on CP^2 within fuzzy geometry

We propose an ansatz for the commutative canonical spin_c Dirac operator on CP^2 in a global geometric approach using the right invariant (left action-) induced vector fields from SU(3). This ansatz is suitable for noncommutative generalisation within the framework of fuzzy geometry. Along the way we identify the physical spinors and construct the canonical spin_c bundle in this formulation. The chirality operator is also given in two equivalent forms. Finally, using representation theory we obtain the eigenspinors and calculate the full spectrum. We use an argument from the fuzzy complex projective space CP^2_F based on the fuzzy analogue of the unprojected spin_c bundle to show that our commutative projected spin_c bundle has the correct SU(3)-representation content.Comment: reduced to 27 pages, minor corrections, minor improvements, typos correcte

Immunopathogenesis of canine chronic ulcerative stomatitis.

Canine Chronic Ulcerative Stomatitis is a spontaneously occurring inflammatory disease of the oral mucosa. An immune-mediated pathogenesis is suspected though not yet proven. We have recently reported on the clinical and histologic features, and identification of select leukocyte cell populations within the lesion. A clinical and histologic similarity to oral lichen planus of people was proposed. In the present study, these initial observations are extended by examining lesions from 24 dogs with clinical evidence of chronic ulcerative stomatitis. Because dogs with chronic ulcerative stomatitis often have concurrent periodontal disease, we wondered if dental plaque/biofilm may be a common instigator of inflammation in both lesions. We hypothesized that dogs with chronic ulcerative stomatitis would exhibit a spectrum of pathologic changes and phenotype of infiltrating leukocytes that would inform lesion pathogenesis and that these changes would differ from inflammatory phenotypes in periodontitis. Previously we identified chronic ulcerative stomatitis lesions to be rich in FoxP3+ and IL17+ cells. As such, we suspect that these leukocytes play an important role in lesion pathogenesis. The current study confirms the presence of moderate to large numbers of FoxP3+ T cells and IL17+ cells in all ulcerative stomatitis lesions using confocal immunofluorescence. Interestingly, the majority of IL17+ cells were determined to be non-T cells and IL17+ cell frequencies were negatively correlated with severity on the clinical scoring system. Three histologic subtypes of ulcerative stomatitis were determined; lichenoid, deep stomatitis and granulomatous. Periodontitis lesions, like stomatitis lesions, were B cell and plasma cell rich, but otherwise differed from the stomatitis lesions. Direct immunofluorescence results did not support an autoantibody-mediated autoimmune disease process. This investigation contributes to the body of literature regarding leukocyte involvement in canine idiopathic inflammatory disease pathogenesis

Effects of reconstituted collagen matrix on fates of mouse embryonic stem cells before and after induction for chondrogenic differentiation

Embryonic stem (ES) cells are pluripotent cells with great potential in regenerative medicine. However, controlling their differentiation toward homogeneous lineages is challenging. In this study, we aim to investigate the effects of reconstituted 3D collagen matrix on the fates of mouse ES (mES) cells before and after induction for chondrogenic differentiation. Specifically, mES cells were encapsulated and cultured in 3D collagen microspheres and exposed to induction signals at different time points. Growth characteristics and differentiation status of mES cells were then evaluated. Collagen microspheres provided a suitable microenvironment supporting mES cell growth and maintaining their undifferentiated status for certain period of time. At later time points, the proportion of undifferentiated mES cells gradually decreased, accompanied by increasing proportions of mesenchymal progenitor cells. This suggests the inductive role of collagen matrix in differentiating mES cells toward mesenchymal lineages. Moreover, a lower initial collagen monomer concentration facilitated the differentiation of mES cells into chondrogenic lineages, while induction at a later time point associated with a more advanced stage of chondrogenic differentiation. This indicates that both the initial collagen concentration and the time to induce differentiation significantly affected the fates of mES cells. This study contributes to future development of ES cell-based therapies. © Copyright 2009, Mary Ann Liebert, Inc.published_or_final_versionThe 7th Annual Meeting of the International Society for Stem Cell Research (ISSCR), Barcelona, Spain, 8-11 July 2009. In Tissue Engineering. Part A, 2009, v. 15 n. 10, p. 3071-308

Decay of Correlations in a Topological Glass

In this paper we continue the study of a topological glassy system. The state space of the model is given by all triangulations of a sphere with $N$ nodes, half of which are red and half are blue. Red nodes want to have 5 neighbors while blue ones want 7. Energies of nodes with other numbers of neighbors are supposed to be positive. The dynamics is that of flipping the diagonal between two adjacent triangles, with a temperature dependent probability. We consider the system at very low temperatures. We concentrate on several new aspects of this model: Starting from a detailed description of the stationary state, we conclude that pairs of defects (nodes with the "wrong" degree) move with very high mobility along 1-dimensional paths. As they wander around, they encounter single defects, which they then move "sideways" with a geometrically defined probability. This induces a diffusive motion of the single defects. If they meet, they annihilate, lowering the energy of the system. We both estimate the decay of energy to equilibrium, as well as the correlations. In particular, we find a decay like $t^{-0.4}$

Extended phase space thermodynamics for charged and rotating black holes and Born-Infeld vacuum polarization

We investigate the critical behaviour of charged and rotating AdS black holes in d spacetime dimensions, including effects from non-linear electrodynamics via the Born-Infeld action, in an extended phase space in which the cosmological constant is interpreted as thermodynamic pressure. For Reissner-Nordstrom black holes we find that the analogy with the Van der Walls liquid-gas system holds in any dimension greater than three, and that the critical exponents coincide with those of the Van der Waals system. We find that neutral slowly rotating black holes in four space-time dimensions also have the same qualitative behaviour. However charged and rotating black holes in three spacetime dimensions do not exhibit critical phenomena. For Born-Infeld black holes we define a new thermodynamic quantity B conjugate to the Born-Infeld parameter b that we call Born-Infeld vacuum polarization. We demonstrate that this quantity is required for consistency of both the first law of thermodynamics and the corresponding Smarr relation.Comment: 23 pages, 32 figures, v2: minor changes, upgraded reference

Adding control to arbitrary unknown quantum operations

While quantum computers promise significant advantages, the complexity of quantum algorithms remains a major technological obstacle. We have developed and demonstrated an architecture-independent technique that simplifies adding control qubits to arbitrary quantum operations-a requirement in many quantum algorithms, simulations and metrology. The technique is independent of how the operation is done, does not require knowledge of what the operation is, and largely separates the problems of how to implement a quantum operation in the laboratory and how to add a control. We demonstrate an entanglement-based version in a photonic system, realizing a range of different two-qubit gates with high fidelity.Comment: 9 pages, 8 figure

Superluminal motion of a relativistic jet in the neutron star merger GW170817

The binary neutron star merger GW170817 was accompanied by radiation across the electromagnetic spectrum and localized to the galaxy NGC 4993 at a distance of 41+/-3 Mpc. The radio and X-ray afterglows of GW170817 exhibited delayed onset, a gradual rise in the emission with time as t^0.8, a peak at about 150 days post-merger, followed by a relatively rapid decline. To date, various models have been proposed to explain the afterglow emission, including a choked-jet cocoon and a successful-jet cocoon (a.k.a. structured jet). However, the observational data have remained inconclusive as to whether GW170817 launched a successful relativistic jet. Here we show, through Very Long Baseline Interferometry, that the compact radio source associated with GW170817 exhibits superluminal motion between two epochs at 75 and 230 days post-merger. This measurement breaks the degeneracy between the models and indicates that, while the early-time radio emission was powered by a wider-angle outflow (cocoon), the late-time emission was most likely dominated by an energetic and narrowly-collimated jet, with an opening angle of <5 degrees, and observed from a viewing angle of about 20 degrees. The imaging of a collimated relativistic outflow emerging from GW170817 adds substantial weight to the growing evidence linking binary neutron star mergers and short gamma-ray bursts.Comment: 42 pages, 4 figures (main text), 2 figures (supplementary text), 2 tables. Referee and editor comments incorporate

Absorptive carbon nanotube electrodes: consequences of optical interference loss in thin film solar cells.

A current bottleneck in the thin film photovoltaic field is the fabrication of low cost electrodes. We demonstrate ultrasonically spray coated multiwalled carbon nanotube (CNT) layers as opaque and absorptive metal-free electrodes deposited at low temperatures and free of post-deposition treatment. The electrodes show sheet resistance as low as 3.4 Ω □(-1), comparable to evaporated metallic contacts deposited in vacuum. Organic photovoltaic devices were optically simulated, showing comparable photocurrent generation between reflective metal and absorptive CNT electrodes for photoactive layer thickness larger than 600 nm when using archetypal poly(3-hexylthiophene) (P3HT) : (6,6)-phenyl C61-butyric acid methyl ester (PCBM) cells. Fabricated devices clearly show that the absorptive CNT electrodes display comparable performance to solution processed and spray coated Ag nanoparticle devices. Additionally, other candidate absorber materials for thin film photovoltaics were simulated with absorptive contacts, elucidating device design in the absence of optical interference and reflection.This research has received partial funding from the Flemish Department of Economics, Science and Innovation. J. G. Tait acknowledges partial funding from the Natural Sciences and Engineering Research Canada. M. De Volder acknowledges partial funding from the ERC Starting grant 337739.This is the author accepted manuscript. The final version is available from the Royal Society of Chemistry via http://dx.doi.org/10.1039/C5NR01119

Quantum Simulation of Spin Chains Coupled to Bosonic Modes with Superconducting Circuits

We propose the implementation of a digital quantum simulation of spin chains coupled to bosonic field modes in superconducting circuits. Gates with high fidelities allows one to simulate a variety of Ising magnetic pairing interactions with transverse field, Tavis-Cummings interaction between spins and a bosonic mode, and a spin model with three-body terms. We analyze the feasibility of the implementation in realistic circuit quantum electrodynamics setups, where the interactions are either realized via capacitive couplings or mediated by microwave resonators.Comment: Chapter in R. S. Anderssen et al. (eds.), Mathematics for Industry 11 (Springer Japan, 2015