Assembly and budding of influenza virus.

Influenza viruses are causative agents of an acute febrile respiratory disease called influenza (commonly known as "flu") and belong to the Orthomyxoviridae family. These viruses possess segmented, negative stranded RNA genomes (vRNA) and are enveloped, usually spherical and bud from the plasma membrane (more specifically, the apical plasma membrane of polarized epithelial cells). Complete virus particles, therefore, are not found inside infected cells. Virus particles consist of three major subviral components, namely the viral envelope, matrix protein (M1), and core (viral ribonucleocapsid [vRNP]). The viral envelope surrounding the vRNP consists of a lipid bilayer containing spikes composed of viral glycoproteins (HA, NA, and M2) on the outer side and M1 on the inner side. Viral lipids, derived from the host plasma membrane, are selectively enriched in cholesterol and glycosphingolipids. M1 forms the bridge between the viral envelope and the core. The viral core consists of helical vRNP containing vRNA (minus strand) and NP along with minor amounts of NEP and polymerase complex (PA, PB1, and PB2). For viral morphogenesis to occur, all three viral components, namely the viral envelope (containing lipids and transmembrane proteins), M1, and the vRNP must be brought to the assembly site, i.e. the apical plasma membrane in polarized epithelial cells. Finally, buds must be formed at the assembly site and virus particles released with the closure of buds. Transmembrane viral proteins are transported to the assembly site on the plasma membrane via the exocytic pathway. Both HA and NA possess apical sorting signals and use lipid rafts for cell surface transport and apical sorting. These lipid rafts are enriched in cholesterol, glycosphingolipids and are relatively resistant to neutral detergent extraction at low temperature. M1 is synthesized on free cytosolic polyribosomes. vRNPs are made inside the host nucleus and are exported into the cytoplasm through the nuclear pore with the help of M1 and NEP. How M1 and vRNPs are directed to the assembly site on the plasma membrane remains unclear. The likely possibilities are that they use a piggy-back mechanism on viral glycoproteins or cytoskeletal elements. Alternatively, they may possess apical determinants or diffuse to the assembly site, or a combination of these pathways. Interactions of M1 with M1, M1 with vRNP, and M1 with HA and NA facilitate concentration of viral components and exclusion of host proteins from the budding site. M1 interacts with the cytoplasmic tail (CT) and transmembrane domain (TMD) of glycoproteins, and thereby functions as a bridge between the viral envelope and vRNP. Lipid rafts function as microdomains for concentrating viral glycoproteins and may serve as a platform for virus budding. Virus bud formation requires membrane bending at the budding site. A combination of factors including concentration of and interaction among viral components, increased viscosity and asymmetry of the lipid bilayer of the lipid raft as well as pulling and pushing forces of viral and host components are likely to cause outward curvature of the plasma membrane at the assembly site leading to bud formation. Eventually, virus release requires completion of the bud due to fusion of the apposing membranes, leading to the closure of the bud, separation of the virus particle from the host plasma membrane and release of the virus particle into the extracellular environment. Among the viral components, M1 contains an L domain motif and plays a critical role in budding. Bud completion requires not only viral components but also host components. However, how host components facilitate bud completion remains unclear. In addition to bud completion, influenza virus requires NA to release virus particles from sialic acid residues on the cell surface and spread from cell to cell. Elucidation of both viral and host factors involved in viral morphogenesis and budding may lead to the development of drugs interfering with the steps of viral morphogenesis and in disease progression

Naturalness, Vacuum Stability and Leptogenesis in the Minimal Seesaw Model

The right-handed neutrinos within the type-I seesaw mechanism can induce large radiative corrections to the Higgs mass, and naturalness arguments can then be used to set limits on their mass scale and Yukawa couplings. Driven by minimality, we consider the presence of two degenerate right-handed neutrinos. We compare the limits from naturalness with the ones from the stability of the electroweak vacuum and from lepton flavor violation. Implications from neutrinoless double beta decay are also discussed and renormalization effects for the light neutrino parameters are presented. Adding small perturbations to the degenerate heavy neutrino spectrum allows for successful leptogenesis.Comment: 22 pages, 11 figures; minor changes; version to appear in Phys. Rev.

Influenza virus morphogenesis and budding.

Influenza viruses are enveloped, negative stranded, segmented RNA viruses belonging to Orthomyxoviridae family. Each virion consists of three major sub-viral components, namely (i) a viral envelope decorated with three transmembrane proteins hemagglutinin (HA), neuraminidase (NA) and M2, (ii) an intermediate layer of matrix protein (M1), and (iii) an innermost helical viral ribonucleocapsid [vRNP] core formed by nucleoprotein (NP) and negative strand viral RNA (vRNA). Since complete virus particles are not found inside the cell, the processes of assembly, morphogenesis, budding and release of progeny virus particles at the plasma membrane of the infected cells are critically important for the production of infectious virions and pathogenesis of influenza viruses as well. Morphogenesis and budding require that all virus components must be brought to the budding site which is the apical plasma membrane in polarized epithelial cells whether in vitro cultured cells or in vivo infected animals. HA and NA forming the outer spikes on the viral envelope possess apical sorting signals and use exocytic pathways and lipid rafts for cell surface transport and apical sorting. NP also has apical determinant(s) and is probably transported to the apical budding site similarly via lipid rafts and/or through cortical actin microfilaments. M1 binds the NP and the exposed RNAs of vRNPs, as well as to the cytoplasmic tails (CT) and transmembrane (TM) domains of HA, NA and M2, and is likely brought to the budding site on the piggy-back of vRNP and transmembrane proteins. Budding processes involve bud initiation, bud growth and bud release. The presence of lipid rafts and assembly of viral components at the budding site can cause asymmetry of lipid bilayers and outward membrane bending leading to bud initiation and bud growth. Bud release requires fusion of the apposing viral and cellular membranes and scission of the virus buds from the infected cellular membrane. The processes involved in bud initiation, bud growth and bud scission/release require involvement both viral and host components and can affect bud closing and virus release in both positive and negative ways. Among the viral components, M1, M2 and NA play important roles in bud release and M1, M2 and NA mutations all affect the morphology of buds and released viruses. Disassembly of host cortical actin microfilaments at the pinching-off site appears to facilitate bud fission and release. Bud scission is energy dependent and only a small fraction of virus buds present on the cell surface is released. Discontinuity of M1 layer underneath the lipid bilayer, absence of outer membrane spikes, absence of lipid rafts in the lipid bilayer, as well as possible presence of M2 and disassembly of cortical actin microfilaments at the pinching-off site appear to facilitate bud fission and bud release. We provide our current understanding of these important processes leading to the production of infectious influenza virus particles

Comment on “Stationary equilibria of self-gravitating quasineutral dusty plasmas” [Phys. Plasmas 8, 4740 (2001)]

It is pointed out that the recently published study on the stationary equilibria of a self-gravitating quasineutral dusty plasma is not correct. The claim of Rao et al. that a “closed form equation for the dust flow speed” [their Eq. (19)] is derived is misleading since a term proportional to the electrostatic potential ϕ0ϕ0 has erroneously been left out. Further, the claim of Rao et al. that the singularities displayed by their Eqs. (19) and (22) at the characteristic speed are due to the inhomogeneity of the self-gravitating potential is devoid of any mathematical merit or physical reasoning. © 2002 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70217/2/PHPAEN-9-12-5135-1.pd

An explanation of the sheath instability

When the sheath accelerates in its plasma–bound motion as a result of the ion response to the electric field, one has a top-heavy equilibrium. In the sheath frame ions are accelerated towards the wall–sheath boundary. In such a situation sheath may become unstable. The sheath instability is examined as the Rayleigh–Taylor (RT) instability and RT growth rate is compared with the reported sheath instability in the literature. © 2003 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69739/2/PHPAEN-10-1-5-1.pd

Numerical investigation of a Hall thruster plasma

The dynamics of the Hall thruster is investigated numerically in the framework of a one-dimensional, multifluid macroscopic description of a partially ionized xenon plasma using finite element formulation. The model includes neutral dynamics, inelastic processes, and plasma–wall interaction. Owing to disparate temporal scales, ions and neutrals have been described by set of time-dependent equations, while electrons are considered in steady state. Based on the experimental observations, a third order polynomial in electron temperature is used to calculate ionization rate. The results show that in the acceleration channel the increase in the ion number density is related to the decrease in the neutral number density. The electron and ion velocity profiles are consistent with the imposed electric field. The electron temperature remains uniform for nearly two-thirds of the channel; then sharply increases to a peak before dropping slightly at the exit. This is consistent with the predicted electron gyration velocity distribution. © 2002 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70486/2/PHPAEN-9-9-4052-1.pd

Isotope thermometery in nuclear multifragmentation

A systematic study of the effect of fragment$-$fragment interaction, quantum statistics, $\gamma$-feeding and collective flow is made in the extraction of the nuclear temperature from the double ratio of the isotopic yields in the statistical model of one-step (Prompt) multifragmentation. Temperature is also extracted from the isotope yield ratios generated in the sequential binary-decay model. Comparison of the thermodynamic temperature with the extracted temperatures for different isotope ratios show some anomaly in both models which is discussed in the context of experimentally measured caloric curves.Comment: uuencoded gzipped file containing 20 pages of text in REVTEX format and 12 figures (Postscript files). Physical Review C (in press

Sistem Pemeliharaan Anjing sebagai Salah Satu Hewan Penular Rabies pada Penderita Rabies di Provinsi Bali Tahun 2011

The number of cases of dog bites in the province of Bali has been a rise high enough. 2009, thenumber of dog bites 21 806 bite, the amount of gain VAR as many as 18 825 people, as many as27 people died. October 16, 2010 the number of bites as much as 44 629 bites, which get the VARas many as 38 982 people, as many as 62 people died. According Disnak (2010) maintance systemof dog conducted by the Balinese tend to be untied so the dogs are freely to enter and out of thehouse. An objective to be achieved in this study was to determine the system of dog maintancewhich is one of the animals transmi! ing rabies (HPR) in patients with rabies in Bali.The study design used was descriptive cross-sectional. The population in this study were all patients who die from the bite of HPR in Bali in 2010-2011, the sample was part of the patientpopulation rabies recorded in Bali Provincial Health O? ce in 2010-2011 with a porpusivesampling techniquePeople with rabies who had HPR were 35.4%, HPR which were not given VAR about 63.6%, andmostly were detachable cages. The reason of had dogs were to guard the house and hobbyists.Dogs that bite the sample were not known who were the owner / wild, so a$ er the bite were notknown its existence, it is di? cult to observe, there were also death but were killed only a smallpart due to illnessIt showed that the mantaince system of dog were not good. The results of this study can be usedas a reference to the stakeholders in order to prevent disease, especially rabies in dogs and themaintenance system. Future studies on rabies vaccination coverage in dogs and the preventionmodel in order to reduce the incidence of rabies in the Bali