NS4B Self-Interaction through Conserved C-Terminal Elements Is Required for the Establishment of Functional Hepatitis C Virus Replication Complexes.

Hepatitis C virus (HCV) is an important human pathogen, persistently infecting more than 170 million individuals worldwide. Studies of the HCV life cycle have become possible with the development of cell culture systems supporting the replication of viral RNA and the production of infectious virus. However, the exact functions of individual proteins, especially of nonstructural protein 4B (NS4B), remain poorly understood. NS4B triggers the formation of specific, vesicular membrane rearrangements, referred to as membranous webs, which have been reported to represent sites of HCV RNA replication. However, the mechanism of vesicle induction is not known. In this study, a panel of 15 mutants carrying substitutions in the highly conserved NS4B C-terminal domain was generated. Five mutations had only a minor effect on replication, but two of them enhanced assembly and release of infectious virus. Ten mutants were replication defective and used for selection of pseudoreversions. Most of the pseudoreversions also localized to the highly conserved NS4B C-terminal domain and were found to restore replication competence upon insertion into the corresponding primary mutant. Importantly, pseudoreversions restoring replication competence also restored heterotypic NS4B self-interaction, which was disrupted by the primary mutation. Finally, electron microscopy analyses of membrane alterations induced by NS4B mutants revealed striking morphological abnormalities, which were restored to wild-type morphology by the corresponding pseudoreversion. These findings demonstrate the important role of the C-terminal domain in NS4B self-interaction and the formation of functional HCV replication complexes.

Genesis of self-organized zebra textures in burial dolomites: Displacive veins, induced stress, and dolomitization

The dolomite veins making up rhythmites common in burial dolomites are not cement infillings of supposed cavities, as in the prevailing view, but are instead displacive veins, veins that pushed aside the host dolostone as they grew. Evidence that the veins are displacive includes a) small transform-fault-like displacements that could not have taken place if the veins were passive cements, and b) stylolites in host rock that formed as the veins grew in order to compensate for the volume added by the veins. Each zebra vein consists of crystals that grow inward from both sides, and displaces its walls via the local induced stress generated by the crystal growth itself. The petrographic criterion used in recent literature to interpret zebra veins in dolomites as cements - namely, that euhedral crystals can grow only in a prior void - disregards evidence to the contrary. The idea that flat voids did form in dolostones is incompatible with the observed optical continuity between the saddle dolomite euhedra of a vein and the replacive dolomite crystals of the host. The induced stress is also the key to the self-organization of zebra veins: In a set of many incipient, randomly-spaced, parallel veins just starting to grow in a host dolostone, each vein¿s induced stress prevents too-close neighbor veins from nucleating, or redissolves them by pressure-solution. The veins that survive this triage are those just outside their neighbors¿s induced stress haloes, now forming a set of equidistant veins, as observed.

Late and post-Hercyniam low temperature veins in the Catalonian Coastal Ranges

Many of the veins enclosed within the Paleozoic basement of the Catalonian Coastal Ranges show severa1 common characteristics: low temperature of formation (between 75 and 200C), the presence of complex polisaline fluids and a certain relationship to the pretriassic paleosurface. Mineralogical composition and age are variable, ranging from Pb-Zn veins with carbonate gangue of late Hercynian age through metal poor fluorite rich veins to barite rich veins of Triasssic age. Mineralizing fluids are not related to late Hercynianmagmatism and deposition took place in active fractures developed either in extensional as in compressive regimes.

The Hercynian ore deposits from the Catalonian Coastal Ranges

Many mineralizations, showings and geochemical anomalies have been found in the Hercynian of the Catalonian Coastal Ranges during the last ten years. Many of them are enclosed in the Paleozoic sediments and volcanics and display pre-metamorphic syngenetic characteristics. The lower carboniferous manganese and base meta1 deposits appear to be formed from hydrothermal fluids springing up in the sea floor through active fractures controlling the filling of the basins in a extensional geotectonic setting. Although less evidence and more controversy is available, similar ore forming processes could have taken place in older Paleozoic times. The deformation and metamorphism have not played an important remobilization role, and most epigenetic deposits of Hercynian age are related to the hydrothermal cells induced by the post-metamorphic granitic intrusives.

Gas identification with tin oxide sensor array and self-organizing maps: adaptive correction of sensor drifts

Low-cost tin oxide gas sensors are inherently nonspecific. In addition, they have several undesirable characteristics such as slow response, nonlinearities, and long-term drifts. This paper shows that the combination of a gas-sensor array together with self-organizing maps (SOM's) permit success in gas classification problems. The system is able to determine the gas present in an atmosphere with error rates lower than 3%. Correction of the sensor's drift with an adaptive SOM has also been investigated

Willigness to pay for long-term care coverage: the role of private information and self-insurance

Both public and private insurance for long-term care is undeveloped in some European countries such as in Spain and empirical evidence is still limited. This paper aims at exmining the determinants of the demand for Long Term Care (LTC) coverage in Spain using contingent valuation techniques. Our findings indicate that only one-fifth of the population is willing to pay to assure coverage decisions are significantly affected by private information asymmetry and housing tenure in giving rise to self-insurance reduces the probability of insurance being hypothetically purchased.

Systematic trends in self-consistent calculations of linear quantum wires

Systematic trends in the properties of a linear split-gate heterojunction are studied by solving iteratively the Poisson and Schrödinger equations for different gate potentials and temperatures. A two-dimensional approximation is presented that is much simpler in the numerical implementation and that accurately reproduces all significant trends. In deriving this approximation, we provide a rigorous and quantitative basis for the formulation of models that assumes a two-dimensional character for the electron gas at the junction.

Ground-state self-consistent calculation of quantum dots under magnetic fields: Addition spectrum

A density-functional self-consistent calculation of the ground-state electronic density of quantum dots under an arbitrary magnetic field is performed. We consider a parabolic lateral confining potential. The addition energy, E(N+1)-E(N), where N is the number of electrons, is compared with experimental data and the different contributions to the energy are analyzed. The Hamiltonian is modeled by a density functional, which includes the exchange and correlation interactions and the local formation of Landau levels for different equilibrium spin populations. We obtain an analytical expression for the critical density under which spontaneous polarization, induced by the exchange interaction, takes place.

Magnetic-field dependence of hole levels in self-assembled InGaAs quantum dots

Recent magnetotransport experiments of holes in InGaAs quantum dots [D. Reuter, P. Kailuweit, A. D. Wieck, U. Zeitler, O. Wibbelhoff, C. Meier, A. Lorke, and J. C. Maan, Phys. Rev. Lett. 94, 026808 (2005)] are interpreted by employing a multiband k¿p Hamiltonian, which considers the interaction between heavy hole and light hole subbands explicitly. No need of invoking an incomplete energy shell filling is required within this model. The crucial role we ascribe to the heavy hole-light hole interaction is further supported by one-band local-spin-density functional calculations, which show that Coulomb interactions do not induce any incomplete hole shell filling and therefore cannot account for the experimental magnetic field dispersion.