The Future of HCV Therapy: NS4B as an Antiviral Target

Chronic hepatitis C virus (HCV) infection is a major worldwide cause of liver disease, including cirrhosis and hepatocellular carcinoma. It is estimated that more than 170 million individuals are infected with HCV, with three to four million new cases each year. The current standard of care, combination treatment with interferon and ribavirin, eradicates the virus in only about 50% of chronically infected patients. Notably, neither of these drugs directly target HCV. Many new antiviral therapies that specifically target hepatitis C (e.g. NS3 protease or NS5B polymerase inhibitors) are therefore in development, with a significant number having advanced into clinical trials. The nonstructural 4B (NS4B) protein, is among the least characterized of the HCV structural and nonstructural proteins and has been subjected to few pharmacological studies. NS4B is an integral membrane protein with at least four predicted transmembrane (TM) domains. A variety of functions have been postulated for NS4B, such as the ability to induce the membranous web replication platform, RNA binding and NTPase activity. This review summarizes potential targets within the nonstructural protein NS4B, with a focus on novel classes of NS4B inhibitors

Probabilistic Fragmentation and Effective Power Law

A simple fragmentation model is introduced and analysed. We show that, under very general conditions, an effective power law for the mass distribution arises with realistic exponent. This exponent has a universal limit, but in practice the effective exponent depends on the detailed breaking mechanism and the initial conditions. This dependence is in good agreement with experimental results of fragmentation.Comment: 4 pages Revtex, 2 figures, zipped and uuencode

Charge rearrangement and screening in a quantum point contact

Compressibility measurements, sensitive to charge rearrangements, are performed on a quantum point contact (QPC). Screening due to mobile charges in the QPC is quantitatively measured, using a second point contact to detect the screened electrical potential. These measurements are performed from pinch-off through the opening of the first few modes in the QPC. While the measured signal closely matches a Thomas-Fermi-Poisson prediction, deviations from the classical behavior, in the form of additional dips, are apparent near the openings of the different modes, with the largest dip at the opening of the first mode. Density functional calculations attribute the first dip to exchange interactions. The other dips reflect the diverging density of states at the opening of each one-dimensional mode, which affects both kinetic and exchange contributions to the energy.Comment: 6 pages, 5 figures. Published in PRL. Supplementary Information is included. Changes: Two references and journal reference adde

Desalination effluents and the establishment of the non-indigenous skeleton shrimp Paracaprella pusilla Mayer, 1890 in the south -eastern Mediterranean

A decade long monitoring programme has revealed a flourishing population of the non-indigenous skeleton shrimp Paracaprella pusilla in the vicinity of outfalls of desalination plants off the Mediterranean coast of Israel. The first specimens were collected in 2010, thus predating all previously published records of this species in the Mediterranean Sea. A decade-long disturbance regime related to the construction and operation of the plants may have had a critical role in driving the population growth.University of Palermo FFR 201

Minimal recipes for global cloudiness

Clouds are primary modulators of Earth’s energy balance. It is thus important to understand the links connecting variabilities in cloudiness to variabilities in other state variables of the climate system, and also describe how these links would change in a changing climate. A conceptual model of global cloudiness can help elucidate these points. In this work we derive simple representations of cloudiness, that can be useful in creating a theory of global cloudiness. These representations illustrate how both spatial and temporal variability of cloudiness can be expressed in terms of basic state variables. Specifically, cloud albedo is captured by a nonlinear combination of pressure velocity and a measure of the low-level stability, and cloud longwave effect is captured by surface temperature, pressure velocity, and standard deviation of pressure velocity. We conclude with a short discussion on the usefulness of this work in the context of global warming response studies

Impact of earthquakes on agriculture during the Roman–Byzantine period from pollen records of the Dead Sea laminated sediment

The Dead Sea region holds the archives of a complex relationship between an ever-changing nature and ancient civilisations. Regional pollen diagrams show a Roman–Byzantine period standing out in the recent millennia by its wetter climate that allowed intensive arboriculture. During that period, the Dead Sea formed laminites that display mostly a seasonal character. A multidisciplinary study focused on two earthquakes, 31 BC and AD 363, recorded as seismites in the Ze’elim gully A unit III which has been well dated by radiocarbon in a previous study. The sampling of the sediment was done at an annual resolution starting from a few years before and finishing a decade after each earthquake. A clear drop in agricultural indicators (especially Olea and cereals) is shown. These pollen indicators mostly reflect human activities in the Judean Hills and coastal oases. Agriculture was disturbed in large part of the rift valley where earthquake damage affected irrigation and access to the fields. It took 4 to 5 yr to resume agriculture to previous conditions. Earthquakes must be seen as contributors to factors damaging societies. If combined with other factors such as climatic aridification, disease epidemics and political upheaval, they may lead to civilisation collapse