DK-1D: a drift-kinetic simulation tool for modelling the shear Alfvén wave and its interaction with collisionless plasma

We present a highly accurate tool for the simulation of shear Alfven waves (SAW) in collisionless plasma. SAW are important in space plasma environments because for small perpendicular scale lengths they can support an electric field parallel to the ambient magnetic field. Electrons can be accelerated by the parallel electric field and these waves have been implicated as the source of vibrant auroral displays. However, the parallel electric field carried by SAW is small in comparison to the perpendicular electric field of the wave, making it difficult to measure directly in the laboratory, or by satellites in the near-Earth plasma environment. In this paper, we present a simulation code that provides a means to study in detail the SAW-particle interaction in both space and laboratory plasma. Using idealised, small-amplitude propagating waves with a single perpendicular wavenumber, the simulation code accurately reproduces the damping rates and parallel electric field amplitudes predicted by linear theory for varying temperatures and perpendicular scale lengths. We present a rigorous kinetic derivation of the parallel electric field strength for small-amplitude SAW and show that commonly-used inertial and kinetic approximations are valid except for where the ratio of thermal to Alfv\'{e}n speed is between 0.7 and 1.0. We also present nonlinear simulations of large-amplitude waves and show that in cases of strong damping, the damping rates and parallel electric field strength deviate from linear predictions when wave energies are greater than only a few percent of the plasma kinetic energy, a situation which is often observed in the magnetosphere. The drift-kinetic code provides reliable, testable predictions of the parallel electric field strength which can be investigated directly in the laboratory, and will help to bridge the gap between studies of SAW in man-made and naturally occuring plasma.

A spectral view of nonlinear fluxes and stationary-transient interaction in the atmosphere

Nonlinear spectral transfers of kinetic energy and enstrophy, and stationary-transient interaction, are studied using global FGGE data for January 1979. It is found that the spectral transfers arise primarily from a combination, in roughly equal measure, of pure transient and mixed stationary-transient interactions. The pure transient interactions are associated with a transient eddy field which is approximately locally homogeneous and isotropic, and they appear to be consistently understood within the context of two-dimensional homogeneous turbulence. Theory based on spatial wale separation concepts suggests that the mixed interactions may be understood physically, to a first approximation, as a process of shear-induced spectral transfer of transient enstrophy along lines of constant zonal wavenumber. This essentially conservative enstrophy transfer generally involves highly nonlocal stationary-transient energy conversions. The observational analysis demonstrates that the shear-induced transient enstrophy transfer is mainly associated with intermediate-scale (zonal wavenumber m > 3) transients and is primarily to smaller (meridional) scales, so that the transient flow acts as a source of stationary energy. In quantitative terms, this transient-eddy rectification corresponds to a forcing timescale in the stationary energy budget which is of the same order of magnitude as most estimates of the damping timescale in simple stationary-wave models (5 to 15 days). Moreover, the nonlinear interactions involved are highly nonlocal and cover a wide range of transient scales of motion.

Severe acute respiratory syndrome coronavirus nonstructural proteins 3, 4, and 6 induce double-membrane vesicles

Coronaviruses (CoV), like other positive-stranded RNA viruses, redirect and rearrange host cell membranes for use as part of the viral genome replication and transcription machinery. Specifically, coronaviruses induce the formation of double-membrane vesicles in infected cells. Although these double-membrane vesicles have been well characterized, the mechanism behind their formation remains unclear, including which viral proteins are responsible. Here, we use transfection of plasmid constructs encoding full-length versions of the three transmembrane-containing nonstructural proteins (nsps) of the severe acute respiratory syndrome (SARS) coronavirus to examine the ability of each to induce double-membrane vesicles in tissue culture. nsp3 has membrane disordering and proliferation ability, both in its full-length form and in a C-terminal-truncated form. nsp3 and nsp4 working together have the ability to pair membranes. nsp6 has membrane proliferation ability as well, inducing perinuclear vesicles localized around the microtubule organizing center. Together, nsp3, nsp4, and nsp6 have the ability to induce double-membrane vesicles that are similar to those observed in SARS coronavirus-infected cells. This activity appears to require the full-length form of nsp3 for action, as double-membrane vesicles were not seen in cells coexpressing the C-terminal truncation nsp3 with nsp4 and nsp6. IMPORTANCE Although the majority of infections caused by coronaviruses in humans are relatively mild, the SARS outbreak of 2002 to 2003 and the emergence of the human coronavirus Middle Eastern respiratory syndrome (MERS-CoV) in 2012 highlight the ability of these viruses to cause severe pathology and fatality. Insight into the molecular biology of how coronaviruses take over the host cell is critical for a full understanding of any known and possible future outbreaks caused by these viruses. Additionally, since membrane rearrangement is a tactic used by all known positive-sense single-stranded RNA viruses, this work adds to that body of knowledge and may prove beneficial in the development of future therapies not only for human coronavirus infections but for other pathogens as well.

Arrays of chiral nanotubes and a layered coordination polymer containing gallium-sulfide supertetrahedral clusters

We report here a unique chiral hybrid gallium sulfide, [NC2H8]2[Ga10S16(N2C12H12)(NC2H7)2] 1, consisting of helical chains of organically-functionalised supertetrahedral clusters which form quadruple-stranded helical nanotubes of ca. 3 nm diameter. This material therefore consists of discrete metal-organic nanotubes which, to the best of our knowledge, are extremely rare. Whilst solvothermal reactions involving 1,2-di(4-pyridyl)ethylene (DPE) resulted in the formation of such single-walled chiral nanotubes, the use of longer 4,4’-trimethylenedipyridine (TMP) ligands resulted in the synthesis of a two-dimensional hybrid gallium sulfide, [C5H6N]3[Ga10S16(OH)(N2C13H14)] 2 in which, for the first time, inorganic and organic linkages between supertetrahedral clusters coexist.

The transient atmospheric response to midlatitude SST anomalies

To study the transient atmospheric response to midlatitude SST anomalies, a three-layer quasigeostrophic (QG) model coupled to a slab oceanic mixed layer in the North Atlantic is used. As diagnosed from a coupled run in perpetual winter conditions, the first two modes of SST variability are linked to the model North Atlantic Oscillation (NAO) and eastern Atlantic pattern (EAP), respectively, the dominant atmospheric modes in the Atlantic sector. The two SST anomaly patterns are then prescribed as fixed anomalous boundary conditions for the model atmosphere, and its transient responses are established from a large ensemble of simulations. In both cases, the tendency of the air–sea heat fluxes to damp the SST anomalies results in an anomalous diabatic heating of the atmosphere that, in turn, forces a baroclinic response, as predicted by linear theory. This initial response rapidly modifies the transient eddy activity and thus the convergence of eddy momentum and heat fluxes. The latter transforms the baroclinic response into a growing barotropic one that resembles the atmospheric mode that had created the SST anomaly in the coupled run and is thus associated with a positive feedback. The total adjustment time is as long as 3–4 months for the NAO-like response and 1–2 months for the EAP-like one. The positive feedback, in both cases, is dependent on the polarity of the SST anomaly, but is stronger in the NAO case, thereby contributing to its predominance at low frequency in the coupled system. However, the feedback is too weak to lead to an instability of the atmospheric modes and primarily results in an increase of their amplitude and persistence and a weakening of the heat flux damping of the SST anomaly.

Evidence for an association with type 2 diabetes mellitus at the PPARG locus in a South Indian population

Peroxisome proliferator-activated receptor-gamma2 (PPARG2) is a nuclear hormone receptor of ligand-dependent transcription factor involved in adipogenesis and a molecular target of the insulin sensitizers thiazolidinediones. We addressed the question of whether the 3 variants (-1279G/A, Pro12Ala, and His478His) in the PPARG2 gene are associated with type 2 diabetes mellitus and its related traits in a South Indian population. The study subjects (1000 type 2 diabetes mellitus and 1000 normal-glucose-tolerant subjects) were chosen randomly from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in southern India. The variants were screened by single-stranded conformational variant, direct sequencing, and restriction fragment length polymorphism. Linkage disequilibrium was estimated from the estimates of haplotypic frequencies. The -1279G/A, Pro12Ala, and His478His variants of the PPARG2 gene were not associated with type 2 diabetes mellitus. However, the 2-loci analyses showed that, in the presence of Pro/Pro genotype of the Pro12Ala variant, the -1279G/A promoter variant showed increased susceptibility to type 2 diabetes mellitus (odds ratio, 2.092; 95% confidence interval, 1.22-3.59; P = .008), whereas in the presence of 12Ala allele, the -1279G/A showed a protective effect against type 2 diabetes mellitus (odds ratio, 0.270; 95% confidence interval, 0.15-0.49; P < .0001). The 3-loci haplotype analysis showed that the A-Ala-T (-1279G/A-Pro12Ala-His478His) haplotype was associated with a reduced risk of type 2 diabetes mellitus (P < .0001). Although our data indicate that the PPARG2 gene variants, independently, have no association with type 2 diabetes mellitus, the 2-loci genotype analysis involving -1279G/A and Pro12Ala variants and the 3-loci haplotype analysis have shown a significant association with type 2 diabetes mellitus in this South Indian population.

Rescue of gene expression by modified REST decoy oligonucleotides in a cellular model of Huntington's disease

Transcriptional dysfunction is a prominent hallmark of Huntington's disease (HD). Several transcription factors have been implicated in the aetiology of HD progression and one of the most prominent is repressor element 1 (RE1) silencing transcription factor (REST). REST is a global repressor of neuronal gene expression and in the presence of mutant Huntingtin increased nuclear REST levels lead to elevated RE1 occupancy and a concomitant increase in target gene repression, including brain-derived neurotrophic factor. It is of great interest to devise strategies to reverse transcriptional dysregulation caused by increased nuclear REST and determine the consequences in HD. Thus far, such strategies have involved RNAi or mutant REST constructs. Decoys are double-stranded oligodeoxynucleotides corresponding to the DNA-binding element of a transcription factor and act to sequester it, thereby abrogating its transcriptional activity. Here, we report the use of a novel decoy strategy to rescue REST target gene expression in a cellular model of HD. We show that delivery of the decoy in cells expressing mutant Huntingtin leads to its specific interaction with REST, a reduction in REST occupancy of RE1s and rescue of target gene expression, including Bdnf. These data point to an alternative strategy for rebalancing the transcriptional dysregulation in HD.

A multi-model analysis of the role of the ocean on the African and Indian monsoon during mid-Holocene

We investigate the role of the ocean feedback on the climate in response to insolation forcing during the mid-Holocene (6,000 year BP) using results from seven coupled ocean–atmosphere general circulation models. We examine how the dipole in late summer sea-surface temperature (SST) anomalies in the tropical Atlantic increases the length of the African monsoon, how this dipole structure is created and maintained, and how the late summer SST warming in the northwest Indian Ocean affects the monsoon retreat in this sector. Similar mechanisms are found in all of the models, including a strong wind evaporation feedback and changes in the mixed layer depth that enhance the insolation forcing, as well as increased Ekman transport in the Atlantic that sharpens the Atlantic dipole pattern. We also consider changes in interannual variability over West Africa and the Indian Ocean. The teleconnection between variations in SST and Sahelian precipitation favor a larger impact of the Atlantic dipole mode in this region. In the Indian Ocean, the strengthening of the Indian dipole structure in autumn has a damping effect on the Indian dipole mode at the interannual time scale

Self-consistent wave-particle interactions in dispersive scale long-period field-line-resonances

Using 1D Vlasov drift-kinetic computer simulations, it is shown that electron trapping in long period standing shear Alfven waves (SAWs) provides an efficient energy sink for wave energy that is much more effective than Landau damping. It is also suggested that the plasma environment of low altitude auroral-zone geomagnetic field lines is more suited to electron acceleration by inertial or kinetic scale Alfven waves. This is due to the self-consistent response of the electron distribution function to SAWs, which must accommodate the low altitude large-scale current system in standing waves. We characterize these effects in terms of the relative magnitude of the wave phase and electron thermal velocities. While particle trapping is shown to be significant across a wide range of plasma temperatures and wave frequencies, we find that electron beam formation in long period waves is more effective in relatively cold plasma.

Numerical analyses of Runge–Kutta implicit–explicit schemes for horizontally explicit, vertically implicit solutions of atmospheric models

With the prospect of exascale computing, computational methods requiring only local data become especially attractive. Consequently, the typical domain decomposition of atmospheric models means horizontally-explicit vertically-implicit (HEVI) time-stepping schemes warrant further attention. In this analysis, Runge-Kutta implicit-explicit schemes from the literature are analysed for their stability and accuracy using a von Neumann stability analysis of two linear systems. Attention is paid to the numerical phase to indicate the behaviour of phase and group velocities. Where the analysis is tractable, analytically derived expressions are considered. For more complicated cases, amplification factors have been numerically generated and the associated amplitudes and phase diagnosed. Analysis of a system describing acoustic waves has necessitated attributing the three resultant eigenvalues to the three physical modes of the system. To do so, a series of algorithms has been devised to track the eigenvalues across the frequency space. The result enables analysis of whether the schemes exactly preserve the non-divergent mode; and whether there is evidence of spurious reversal in the direction of group velocities or asymmetry in the damping for the pair of acoustic modes. Frequency ranges that span next-generation high-resolution weather models to coarse-resolution climate models are considered; and a comparison is made of errors accumulated from multiple stability-constrained shorter time-steps from the HEVI scheme with a single integration from a fully implicit scheme over the same time interval. Two schemes, “Trap2(2,3,2)” and “UJ3(1,3,2)”, both already used in atmospheric models, are identified as offering consistently good stability and representation of phase across all the analyses. Furthermore, according to a simple measure of computational cost, “Trap2(2,3,2)” is the least expensive.

Competitive fitness in coronaviruses is not correlated with size or number of double-membrane vesicles under reduced-temperature growth conditions

Positive-stranded viruses synthesize their RNA in membrane-bound organelles, but it is not clear how this benefits the virus or the host. For coronaviruses, these organelles take the form of double-membrane vesicles (DMVs) interconnected by a convoluted membrane network. We used electron microscopy to identify murine coronaviruses with mutations in nsp3 and nsp14 that replicated normally while producing only half the normal amount of DMVs. Viruses with mutations in nsp5 and nsp16 produced small DMVs but also replicated normally. Quantitative RT-PCR confirmed that the most strongly affected of these, the nsp3 mutant, produced more viral RNA than wild-type virus. Competitive growth assays were carried out in both continuous and primary cells to better understand the contribution of DMVs to viral fitness. Surprisingly, several viruses that produced fewer or smaller DMVs showed a higher relative fitness compared to wild-type virus, suggesting that larger and more numerous DMVs do not necessarily confer a competitive advantage in primary or continuous cell culture. For the first time, this directly demonstrates that replication and organelle formation may be, at least in part, studied separately during positive-stranded RNA virus infection.

Untangling membrane rearrangement in the Nidovirales

All known positive sense single-stranded RNA viruses induce host cell membrane rearrangement for purposes of aiding viral genome replication and transcription. Members of the Nidovirales order are no exception, inducing intricate regions of double membrane vesicles and convoluted membranes crucial for the production of viral progeny. Although these structures have been well studied for some members of this order, much remains unclear regarding the biogenesis of these rearranged membranes. Here, we discuss what is known about these structures and their formation, compare some of the driving viral proteins behind this process across the nidovirus order, and examine possible routes of mechanism by which membrane rearrangement may occur.

Transient atmospheric response to interactive SST anomalies

The transient atmospheric response to interactive SST anomalies in the midlatitudes is investigated using a three-layer QG model coupled in perpetual winter conditions to a slab oceanic mixed layer in the North Atlantic. The SST anomalies are diagnosed from a coupled run and prescribed as initial conditions, but are free to evolve. The initial evolution of the atmospheric response is similar to that obtained with a prescribed SST anomaly, starting as a quasi-linear baroclinic and then quickly evolving into a growing equivalent barotropic one. Because of the heat flux damping, the SST anomaly amplitude slowly decreases, albeit with little change in pattern. Correspondingly, the atmospheric response only increases until it reaches a maximum amplitude after about 1–3.5 months, depending on the SST anomaly considered. The response is similar to that at equilibrium in the fixed SST case, but it is 1.5–2 times smaller, and then slowly decays away.

Mixed layer lateral eddy fluxes mediated by air-sea interaction

The modulation of air–sea heat fluxes by geostrophic eddies due to the stirring of temperature at the sea surface is discussed and quantified. It is argued that the damping of eddy temperature variance by such air–sea fluxes enhances the dissipation of surface temperature fields. Depending on the time scale of damping relative to that of the eddying motions, surface eddy diffusivities can be significantly enhanced over interior values. The issues are explored and quantified in a controlled setting by driving a tracer field, a proxy for sea surface temperature, with surface altimetric observations in the Antarctic Circumpolar Current (ACC) of the Southern Ocean. A new, tracer-based diagnostic of eddy diffusivity is introduced, which is related to the Nakamura effective diffusivity. Using this, the mixed layer lateral eddy diffusivities associated with (i) eddy stirring and small-scale mixing and (ii) surface damping by air–sea interaction is quantified. In the ACC, a diffusivity associated with surface damping of a comparable magnitude to that associated with eddy stirring (;500 m2 s21) is found. In frontal regions prevalent in the ACC, an augmentation of surface lateral eddy diffusivities of this magnitude is equivalent to an air–sea flux of 100 W m22 acting over a mixed layer depth of 100 m, a very significant effect. Finally, the implications for other tracer fields such as salinity, dissolved gases, and chlorophyll are discussed. Different tracers are found to have surface eddy diffusivities that differ significantly in magnitude.

Resonance response of electrorheological fluids in vertical oscillation squeeze flow

The resonance effect of microcrystalline cellulose/castor oil electrorheological (ER) suspensions was studied in a compressed oscillatory squeeze flow under external electric fields. The resonance frequency first increases linearly with increasing external held, and then shift to high-field plateau. The amplitudes of resonance peak increase sharply with the applied fields in the range of 0.17-1.67kV/mm. The phase difference of the reduced displacement relative to the excitation force inverses in the case of resonance. A viscoelasticity model of the ER suspensions, which offers both the equivalent stiffness and the viscous damping, should be responsible for the appearance of resonance. The influence of the electric field on the resonance frequency and the resonance hump is consistent qualitatively with the interpretation of our proposed model. Storage modulus G' was presented for the purpose of investigating this influence.