Genetic variability of hepatitis C virus before and after combined therapy of interferon plus ribavirin

We present an analysis of the selective forces acting on two hepatitis C virus genome regions previously postulated to be involved in the viral response to combined antiviral therapy. One includes the three hypervariable regions in the envelope E2 glycoprotein, and the other encompasses the PKR binding domain and the V3 domain in the NS5A region. We used a cohort of 22 non-responder patients to combined therapy (interferon alpha-2a plus ribavirin) for which samples were obtained before initiation of therapy and after 6 or/and 12 months of treatment. A range of 25-100 clones per patient, genome region and time sample were sequenced. These were used to detect general patterns of adaptation, to identify particular adaptation mechanisms and to analyze the patterns of evolutionary change in both genome regions. These analyses failed to detect a common adaptive mechanism for the lack of response to antiviral treatment in these patients. On the contrary, a wide range of situations were observed, from patients showing no positively selected sites to others with many, and with completely different topologies in the reconstructed phylogenetic trees. Altogether, these results suggest that viral strategies to evade selection pressure from the immune system and antiviral therapies do not result from a single mechanism and they are likely based on a range of different alternatives, in which several different changes, or their combination, along the HCV genome confer viruses the ability to overcome strong selective [email protected]; [email protected]; [email protected]; [email protected]; [email protected]; [email protected]; [email protected]; [email protected]

Towards reconciling structure and function in the nuclear pore complex

The spatial separation between the cytoplasm and the cell nucleus necessitates the continuous exchange of macromolecular cargo across the double-membraned nuclear envelope. Being the only passageway in and out of the nucleus, the nuclear pore complex (NPC) has the principal function of regulating the high throughput of nucleocytoplasmic transport in a highly selective manner so as to maintain cellular order and function. Here, we present a retrospective review of the evidence that has led to the current understanding of both NPC structure and function. Looking towards the future, we contemplate on how various outstanding effects and nanoscopic characteristics ought to be addressed, with the goal of reconciling structure and function into a single unified picture of the NPC

Cationic polyelectrolytes: A new look at their possible roles as opsonins, as stimulators of respiratory burst in leukocytes, in bacteriolysis, and as modulators of immune-complex diseases (A review hypothesis)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44497/1/10753_2004_Article_BF00915991.pd

Characterization of the surfaces of hydrogen-passivated silicon by STM

Hydrogen-passivated silicon (amorphous, microcrystalline or crystalline silicon) is characterized by a low density of surface states. Thus, standard tunnelling theory, which relies on tunnelling at the Fermi energy, may not be applicable to this class of materials and it may be difficult to optimize scanning tunnelling microscopy. We performed simultaneous measurements of topography (by constant-current imaging) and of the distribution of the local apparent barrier height, phi(A), as a function of the tunnelling voltage on hydrogen-passivated, misoriented Si(111) samples that were prepared by etching with NH4F solution. Tunnelling conditions were identified, which allow the characterization of inhomogeneities related to both local roughness and chemical composition. (C) 2000 Elsevier Science S.A. All rights reserved

Nucleation and growth of hydrogenated microcrystalline silicon films : new insights from scanning probe microscopies

For mixed-phase films prepared by plasma enhanced chemical vapour deposition the density of crystallites in an amorphous matrix was measured as a function of the hydrogen-dilution of the source gas. General features of the observed growth mode can be described in terms of a genuine surface model incorporating autocatalytic crystallization. We investigated the chemical transport of silicon-related species in a hydrogen plasma and found it to be of major importance under the present conditions. The results cast some doubts on previous concepts relating to the existence of a growth zone and of amorphous incubation layers as observed by in-situ ellipsometry

Nucleation and growth analysis of microcrystalline silicon by scanning probe microscopy : substrate dependence, local structural and electron properties of As-grown surfaces

Nucleation and growth of hydrogenated microcrystalline silicon films are investigated by scanning probe microscopy and spectroscopy of as-grown firms. We measure highly doped films grown on oxidized silicon and discuss nucleation of crystallites in comparison with hydrogen-passivated substrates. It turns out that the oxidized substrate mediates nucleation. This mechanism is preferred over nucleation on hydrogenated amorphous silicon. For films as thin as a few nanometers we demonstrate that scanning tunneling microscopy and spectroscopy are capable of spatially resolving structural and electronic surface properties. Amorphous and microcrystalline surface elements are distinguished by different types of tunneling spectra showing by a factor of similar to 5 a larger rectification for crystallites. (C) 2000 Elsevier Science B.V. All rights reserved

Nucleation and growth of low-temperature fine-crystalline silicon : a scanning probe microscopy and Raman spectroscopy study of the influence of hydrogen and different substrates

Low-temperature fine-crystalline silicon films grown by plasma-enhanced chemical vapour deposition (PECVD) on different substrates are investigated by scanning probe microscopy and Raman spectroscopy. By this, more insight into nucleation and growth of crystallites is provided. For this purpose deposition conditions within the transition regime from fine-crystalline to amorphous growth are chosen leading to the growth of individual crystallites embedded in an amorphous matrix. Effects of the type of substrate and of hydrogen dilution are studied. Films grown on naturally oxidized Si(100) and on graphite(0001) show a clear correlation between the area density of crystallites as inspected from surface micrographs and the volume fraction of crystalline phase as detected by Raman spectroscopy. Nucleation of crystallites takes place within a narrow range of film thickness (the first few 10 nm for growth on silicon oxide) whereas the subsequent growth stage exclusively promotes the continuous growth of existing crystallites, i.e. nucleation of new crystallites is suppressed. The initial nucleation strongly depends on the type of substrate, for instance purely amorphous films can grow instead of two-phase ones if only the oxidized Si(100) substrate is replaced by Si(100) which has been hydrogen passivated by a HF treatment. A pronounced influence of hydrogen on crystallite nucleation is observed: if the source gas ratio R = SiH4/(SiH4 + H-2) is reduced by only 0.3% the nucleation density increases by about one order of magnitude. In addition to presently discussed kinetic growth models the results indicate the applicability of a thermodynamical concept for explaining the structural evolution. (C) 2000 Elsevier Science S.A. All rights reserved