3‐O‐Sulfation of Heparan Sulfate Enhances Tau Interaction and Cellular Uptake

Prion‐like transcellular spreading of tau in Alzheimer's Disease (AD) is mediated by tau binding to cell surface heparan sulfate (HS). However, the structural determinants for tau–HS interaction are not well understood. Microarray and SPR assays of structurally defined HS oligosaccharides show that a rare 3‐O‐sulfation (3‐O‐S) of HS significantly enhances tau binding. In Hs3st1^?/? (HS 3‐O‐sulfotransferase‐1 knockout) cells, reduced 3‐O‐S levels of HS diminished both cell surface binding and internalization of tau. In a cell culture, the addition of a 3‐O‐S HS 12‐mer reduced both tau cell surface binding and cellular uptake. NMR titrations mapped 3‐O‐S binding sites to the microtubule binding repeat 2 (R2) and proline‐rich region 2 (PRR2) of tau. Tau is only the seventh protein currently known to recognize HS 3‐O‐sulfation. Our work demonstrates that this rare 3‐O‐sulfation enhances tau–HS binding and likely the transcellular spread of tau, providing a novel target for disease‐modifying treatment of AD and other tauopathies.     

Nanoparticles from vesicle polymerization: Characterization and kinetic study

The polymerization of isodecyl acrylate (ISODAC) in vesicles made from an anionic surfactant—sodium di-2-ethylhexyl phosphate (SEHP)—and from water is studied by ¹H-NMR, transmission electron microscopy, and quasielastic light scattering. High polymerization rates and high conversion rates are achieved with both water-soluble initiator, K₂S₂O₈ (potassium persulfate), and oil-soluble initiator, AIBN (azoisobisbutyronitrile). ISODAC is probably located inside the vesicle bilayer(s) because of its high hydrophobicity. Particles stable at room temperature with a mean diameter of about 50 nm are obtained. Kinetic orders of ISODAC polymerization are determined and the characterization of the resulting particles during and after polymerization are studied. © 1996 John Wiley & Sons, Inc.     

Some features of the solid-state polymerization of diacetylenes

Simple models of the initial polymerization stage and the polymerization kinetics are considered on the example of the solid state topochemical polymerization of diacetylenes. These models take into account the reaction specifity of the solid state process and the nonlinear character of the monomer units interactions.     

Moderately concentrated solutions of polystyrene,part 5. Static and dynamic light scattering in bis(2-ethylhexyl) phthalate

Static and dynamic light scattering data are reported on dilute and moderately concentrated solutions of a high molecular weight polystyrene (M_w = 3.61 × 10⁶) in bis(2-ethylhexyl) phthalate under Flory Theta conditions. The data cover a concentration range with 0.03 × [η]c × 3.5, with several concentrations large enough that the product cM^w exceeds the value necessary for entanglement behavior. The results show that a certain intermolecular scattering function H(q, c) often approximated by unity should not be neglected in the evaluation of the correlation length in the static scattering from moderately concentrated solutions of flexible chain polymers. An approximate form for H(q, c) for moderately concentrated solutions is consistent with a soft spherically symmetric repulsive potential among the chains. The dynamic scattering show two distinct groups of relaxation rates at all concentrations, but the interpretation of the two modes changes as the concentration increases from low concentrations ([η]c < 1) to higher concentrations. At low concentrations the slower mode corresponds to mutual diffusion, and the faster mode to intramolecular dynamics. For concentrations with [η]c > 2.4 the slow mode is viscoelastic in origin, and the faster mode is diffusive. The behavior is compared with theoretical predictions in both regimes.     

High-frequency ultrasound backscattering by blood: analytical and semianalytical models of the erythrocyte cross section

This paper proposes analytical and semianalytical models of the ultrasonic backscattering cross section (BCS) of various geometrical shapes mimicking a red blood cell (RBC) for frequencies varying from 0 to 90 MHz. By assuming the first-order Born approximation and by modeling the shape of a RBC by a realistic biconcave volume, different scattering behaviors were identified for increasing frequencies. For frequencies below 18 MHz, a RBC can be considered a Rayleigh scatterer. For frequencies less than 39 MHz, the general concept of acoustic inertia tensor is introduced to describe the variation of the BCS with the frequency and the incidence direction. For frequencies below 90 MHz, ultrasound backscattering by a RBC is equivalent to backscattering by a cylinder of height 2 microm and diameter 7.8 microm. These results lay the basis of ultrasonic characterization of RBC aggregation by proposing a method that distinguishes the contribution of the individual RBC acoustical characteristics from collective effects, on the global blood backscattering coefficient. A new method of data reduction that models the frequency dependence of the ultrasonic BCS of micron-sized weak scatterers is also proposed. Applications of this method are in tissue characterization as well as in hematology.     

Composing dinatural transformations: Towards a calculus of substitution

Dinatural transformations, which generalise the ubiquitous natural transformations to the case where the domain and codomain functors are of mixed variance, fail to compose in general; this has been known since they were discovered by Dubuc and Street in 1970. Many ad hoc solutions to this remarkable shortcoming have been found, but a general theory of compositionality was missing until Petri?, in 2003, introduced the concept of g-dinatural transformations, that is, dinatural transformations together with an appropriate graph: he showed how acyclicity of the composite graph of two arbitrary dinatural transformations is a sufficient and essentially necessary condition for the composite transformation to be in turn dinatural. Here we propose an alternative, semantic rather than syntactic, proof of Petri?'s theorem, which the authors independently rediscovered with no knowledge of its prior existence; we then use it to define a generalised functor category, whose objects are functors of mixed variance in many variables, and whose morphisms are transformations that happen to be dinatural only in some of their variables.We also define a notion of horizontal composition for dinatural transformations, extending the well-known version for natural transformations, and prove it is associative and unitary. Horizontal composition embodies substitution of functors into transformations and vice-versa, and is intuitively reflected from the string-diagram point of view by substitution of graphs into graphs.This work represents the first, fundamental steps towards a substitution calculus for dinatural transformations as sought originally by Kelly, with the intention then to apply it to describe coherence problems abstractly. There are still fundamental difficulties that are yet to be overcome in order to achieve such a calculus, and these will be the subject of future work; however, our contribution places us well in track on the path traced by Kelly towards a calculus of substitution for dinatural transformations.     

Detection of multicomponent signals: effect of difference in level between components

The detection of multicomponent signals for which the components are not equidetectable is precisely investigated as a function of the level difference ΔL(i∕j) between components. The detection thresholds are determined for a seven-tone complex signal with random starting phases masked by white noise. Level differences between the components are examined. A model for non-equidetectable conditions based on the statistical summation model is described. The improvement in detection is calculated from the level difference between components that is related to the thresholds for single components. The model predictions are in accordance with the experimental results.     

Subpicosecond pulse generation from a 1.56 μm mode-locked VECSEL

Near-transform-limited subpicosecond pulses at 1.56 μm were generated from an optically pumped InP-based vertical-external-cavity surface-emitting laser (VECSEL) passively mode-locked at 2 GHz repetition rate with a fast InGaAsNSb/GaAs semiconductor saturable absorber mirror (SESAM). The SESAM microcavity resonance was adjusted via a selective etching of phase layers specifically designed to control the magnitude of both the modulation depth and the intracavity group delay dispersion of the SESAM. Using the same VECSEL chip, we observed that the mode-locked pulse duration could be reduced from several picoseconds to less than 1 ps with a detuned resonant SESAM.     

Construction of grand unified models under maximal subalgebras

A construction of grand unified models of the strong, weak and electromagnetic interactions is described based on the transformation properties of the group generators under a maximal subgroup decomposition without recourse to large representation matrices or to the specific algebraic structures of some classical Lie-groups, such as the Clifford algebra associated with the orthogonal groups or the octonionic structure of the exceptional groups. To illustrate the procedure an explicit construction is given of the SU(5) model useful in the discussion of higher rank groups, of SO(10) under the maximal subalgebras SU(2)_L × SU(2)_R × SU(4)_c and SU(5) × U(1)_r and of the exceptional group E₆ under SU(3)_L × SU(3)_R × SU(3)_c and SO(10) × U(1)_t. The construction procedure can be used as well with any classical Lie-group.