New tricks for KDEL receptors

published_or_final_versio

LES-RANS of installed ultra-high-bypass-ratio coaxial jet aeroacoustics with flight stream

EPSRC EP/L000261/1; EU-funded project “JERONIMO” (ACP2-GA-2012-314692-JERONIMO

Towards robust unstructured turbomachinery large eddy simulation

This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.compfluid.2015.06.017Industrial legacy codes usually have had long pedigrees within companies, and are deeply embedded into design processes. As the affordability and availability of computing power has increased, these codes have found themselves pushed into service as large eddy simulation solvers. The approximate Riemann solver of Roe, which is frequently used as the core method in such legacy codes, is shown to need much user care when adopted as the discretisation scheme for large eddy simulation. A kinetic energy preserving (KEP) scheme—which retains the same advantageous stencil and communications halo as the original Roe scheme—is instead implemented and tested. The adaptations of code required to switch between the two schemes were found to be extremely straightforward. As the KEP scheme intrinsically bounds the growth of the kinetic energy, it is significantly more stable than the classical non-dissipative schemes. This means that the expensive smoothing terms of the Roe scheme are not always necessary. Instead, an explicit subgrid scale turbulence model can be sensibly applied. As such, a range of mixed linear–non-linear turbulence models are tested. The performance of the KEP scheme is then tested against that of the Roe for canonical flows and engine-realistic turbine blade cutback trailing edge cases. The new KEP scheme is found to perform better than the original in all cases. A range of mesh topologies: hexahedral; prismatic; and tetrahedral; are also tested with both schemes, and the KEP scheme is again found to perform significantly better on all mesh types for these flows.This work was supported by an iCASE studentship from the Engineering and Physical Sciences Research Council, via Rolls-Royce plc. The funding from both organisations is gratefully acknowledged

Class II ADP-ribosylation factors are required for efficient secretion of Dengue viruses

This article is available open access through the publisher’s website.Identification and characterization of virus-host interactions are very important steps toward a better understanding of the molecular mechanisms responsible for disease progression and pathogenesis. To date, very few cellular factors involved in the life cycle of flaviviruses, which are important human pathogens, have been described. In this study, we demonstrate a crucial role for class II Arf proteins (Arf4 and Arf5) in the dengue flavivirus life cycle. We show that simultaneous depletion of Arf4 and Arf5 blocks recombinant subviral particle secretion for all four dengue serotypes. Immunostaining analysis suggests that class II Arf proteins are required at an early pre-Golgi step for dengue virus secretion. Using a horseradish peroxidase protein fused to a signal peptide, we show that class II Arfs act specifically on dengue virus secretion without altering the secretion of proteins through the constitutive secretory pathway. Co-immunoprecipitation data demonstrate that the dengue prM glycoprotein interacts with class II Arf proteins but not through its C-terminal VXPX motif. Finally, experiments performed with replication-competent dengue and yellow fever viruses demonstrate that the depletion of class II Arfs inhibits virus secretion, thus confirming their implication in the virus life cycle, although data obtained with West Nile virus pointed out the differences in virus-host interactions among flaviviruses. Our findings shed new light on a molecular mechanism used by dengue viruses during the late stages of the life cycle and demonstrate a novel function for class II Arf proteins.Research Fund for Control of Infectious Diseases of Hong Kong and BNP Paribas Corporate and Investment Banking

Influence of gouge thickness and grain size on permeability of macrofractured basalt

Fractures allow crystalline rocks to store and transport fluids, but fracture permeability can also be influenced significantly by the existence or absence of gouge and by stress history. To investigate these issues, we measured the water permeability of macrofractured basalt samples unfilled or infilled with gouge of different grain sizes and thicknesses as a function of hydrostatic stress and also under cyclic stress conditions. In all experiments, permeability decreased with increasing effective pressure, but unfilled fractures exhibited a much greater decrease than gouge-filled fractures. Macrofractures filled with fine-grained gouge had the lowest permeabilities and exhibited the smallest change with pressure. By contrast, the permeability changed significantly more in fractures filled with coarser-grained gouge. During cyclic pressurization, permeability decreased with increasing cycle number until reaching a minimum value after a certain number of cycles. Permeability reduction in unfilled fractures is accommodated by both elastic and inelastic deformation of surface asperities, while measurements of the particle size distribution and compaction in gouge-filled fractures indicate only inelastic compaction. In fine-grained gouge this is accommodated by grain rearrangement, while in coarser-grained gouge it is the result of both grain rearrangement and comminution. Overall, sample permeability is dominated by the gouge permeability, which decreases with increasing thickness and is also sensitive to the grain size and its distribution. Our results imply that there is a crossover depth in the crust below which the permeability of well-mated fractures (e.g., joints) becomes lower than that of gouge-filled fractures (e.g., shear faults)

Quantifying drug-induced dyskinesias in the arms using digitised spiral-drawing tasks.

In this study, we quantify the severity of drug-induced dyskinesias in the arms of Parkinson's disease (PD) patients using digitised spiral-drawing tasks. Two spiral drawings, namely a circular and a square spiral, are designed to, respectively, represent the continuous and discrete arm motions, and the size of the spiral is decided so that both the distal and proximal arm joints are involved. Fifteen PD patients, average disease duration 14.4+/-7.4 years, were assessed 30 min after a levodopa challenge whilst performing circular and square spiral-drawing tasks. The velocity of drawing movements was computed and the amplitude of the involuntary dyskinetic movements was measured as the standard deviation of the drawing velocity (SD-DV). The mean amplitude of dyskinetic movements was compared between arms and tasks and was correlated with clinical measures including the Bain dyskinesia scale and the total unified Parkinson's disease rating scale (UPDRS) score. The results showed that there was no statistically significant difference in the amplitude of dyskinesias either between the arms or between the continuous (circular) and discrete (square) spiral drawings in this group of PD patients, but interestingly the interaction between arm and drawing pattern was significant. Significant correlations were found between the magnitude of dyskinesia measured from the spiral-drawing tasks and both the 'on' or 'off' UPDRS and also the Bain dyskinesia scale. We conclude that the drawing tasks may be used to provide an objective method of quantifying the severity of drug-induced dyskinesias in the arm in PD patients

Spinor Bose-Einstein condensates in double-well potentials

We consider the statics and dynamics of F = 1 spinor Bose–Einstein condensates (BECs) confined in double-well potentials. We use a two-mode Galerkin-type quasi-analytical approximation to describe the stationary states of the system. This way, we are able to obtain not only earlier results based on the single-mode approximation (SMA) frequently used in studies of spinor BECs, but also additional modes that involve either two or all three spinor components of the F = 1 spinor BEC. The results based on this Galerkin-type decomposition are in good agreement with the analysis of the full system. We subsequently analyze the stability of these multi-component states, as well as their dynamics when we find them to be unstable. The instabilities of the symmetric or anti-symmetric states exhibit symmetry-breaking and recurrent asymmetric patterns. Our results yield qualitatively similar bifurcation diagrams both for polar (such as 23Na) and ferromagnetic (such as 87Rb) spinor BECs

Investigation of the functional roles of host cell proteins involved in Coronavirus infection using highly specific and scalable RNA interference (RNAi) approach

Since its identification in the 1990s, the RNA interference (RNAi) pathway has proven extremely useful in elucidating the function of proteins in the context of cells and even whole organisms. In particular, this sequence-specific and powerful loss-of-function approach has greatly simplified the study of the role of host cell factors implicated in the life cycle of viruses. Here, we detail the RNAi method we have developed and used to specifically knock down the expression of ezrin, an actin binding protein that was identified by yeast two-hybrid screening to interact with the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) spike (S) protein. This method was used to study the role of ezrin, specifically during the entry stage of SARS-CoV infection

Myocardial deletion of Smad4 using a novel alpha skeletal muscle actin Cre recombinase transgenic mouse causes misalignment of the cardiac outflow tract

S MAD4 acts as the converging point f or T GF β and BMP signaling in heart development. Here, we investigated the role of S MAD4 in heart development usi ng a novel α skeletal muscle actin Cre recombinase (MuCre) transgenic mouse strain. Lineage tracing using MuCre/ROSA26LacZ reporter mice indicated strong Cre-recombinase expression in developing and adult heart and skeletal muscles. In heart development, significant MuCre expression was noted at E11.5 in the atrial, ventricular, outflow tract and atrioventricular canal myocardium, but not in the endocardial cushions. MuCre-driven conditional deletion of Smad4 in mice caused double outlet right ventricle (DORV), ventricular septal defect (VSD), impaired trabeculation and thinning of ventricular myocardium, and mid-gestational embryonic lethality. In conclusion, MuCre mice effectively delete genes in both heart and skeletal muscles, thus enabling the discovery that myocardial Smad4 deletion causes misalignment of the outflow tract and DORV