Stall Inception in Low-Pressure Ratio Fans

A combined experimental and computational test program, with two low-pressure ratio aero-engine fans, has been used to identify the flow mechanisms at stall inception and the subsequent stall cell growth. The two fans have the same rotor tip clearance, annulus design, and downstream stators, but different levels of tip loading. The measurement data show that both the fans stall via spike-type inception, but that the growth of the stall cell and the final cell size is different in each fan. The computations, reproducing both the qualitative and quantitative behavior of the steady-state and transient measurements, are used to identify the flow mechanisms at the origin of stall inception. In one fan, spillage of tip leakage flow upstream of the leading edge plane is responsible. In the other, sudden growth of casing corner separation blockage leads to stall. These two mechanisms are in accord with the findings from core compressors. However, the transonic aerodynamics and the low hub-to-tip radius ratio of the fans lead to the following two findings: first, the casing corner separation is driven by shock-boundary layer interaction and second, the spanwise loading distribution of the fan determines whether the spike develops into full-span or part-span stall and both types of behavior are represented in the present work. Finally, the axial momentum flux of the tip clearance flow is shown to be a useful indicator of the leakage jet spillage mechanism. A simple model is provided that links the tip loading, stagger, and solidity with the tip clearance axial momentum flux, thereby allowing the aerodynamicist to connect, qualitatively, design parameters with the stall behavior of the fan.</jats:p

Mechanisms of viral entry: sneaking in the front door

Recent developments in methods to study virus internalisation are providing clearer insights into mechanisms used by viruses to enter host cells. The use of dominant negative constructs, specific inhibitory drugs and RNAi to selectively prevent entry through particular pathways has provided evidence for the clathrin-mediated entry of hepatitis C virus (HCV) as well as the caveolar entry of Simian Virus 40. Moreover, the ability to image and track fluorescent-labelled virus particles in real-time has begun to challenge the classical plasma membrane entry mechanisms described for poliovirus and human immunodeficiency virus. This review will cover both well-documented entry mechanisms as well as more recent discoveries in the entry pathways of enveloped and non-enveloped viruses. This will include viruses which enter the cytosol directly at the plasma membrane and those which enter via endocytosis and traversal of internal membrane barrier(s). Recent developments in imaging and inhibition of entry pathways have provided insights into the ill-defined entry mechanism of HCV, bringing it to the forefront of viral entry research. Finally, as high-affinity receptors often define viral internalisation pathways, and tropism in vivo, host membrane proteins to which viral particles specifically bind will be discussed throughout

PI3Kinase signaling in glioblastoma

Glioblastoma (GBM) is the most common primary tumor of the CNS in the adult. It is characterized by exponential growth and diffuse invasiveness. Among many different genetic alterations in GBM, e.g., mutations of PTEN, EGFR, p16/p19 and p53 and their impact on aberrant signaling have been thoroughly characterized. A major barrier to develop a common therapeutic strategy is founded on the fact that each tumor has its individual genetic fingerprint. Nonetheless, the PI3K pathway may represent a common therapeutic target to most GBM due to its central position in the signaling cascade affecting proliferation, apoptosis and migration. The read-out of blocking PI3K alone or in combination with other cancer pathways should mainly focus, besides the cytostatic effect, on cell death induction since sublethal damage may induce selection of more malignant clones. Targeting more than one pathway instead of a single agent approach may be more promising to kill GBM cells

A HIV-1 Tat mutant protein disrupts HIV-1 Rev function by targeting the DEAD-box RNA helicase DDX1

BACKGROUND: Previously we described a transdominant negative mutant of the HIV-1 Tat protein, termed Nullbasic, that downregulated the steady state levels of unspliced and singly spliced viral mRNA, an activity caused by inhibition of HIV-1 Rev activity. Nullbasic also altered the subcellular localizations of Rev and other cellular proteins, including CRM1, B23 and C23 in a Rev-dependent manner, suggesting that Nullbasic may disrupt Rev function and trafficking by intervening with an unidentified component of the Rev nucleocytoplasmic transport complex. RESULTS: To seek a possible mechanism that could explain how Nullbasic inhibits Rev activity, we used a proteomics approach to identify host cellular proteins that interact with Nullbasic. Forty-six Nullbasic-binding proteins were identified by mass spectrometry including the DEAD-box RNA helicase, DDX1. To determine the effect of DDX1 on Nullbasic-mediated Rev activity, we performed cell-based immunoprecipitation assays, Rev reporter assays and bio-layer interferometry (BLI) assays. Interaction between DDX1 and Nullbasic was observed by co-immunoprecipitation of Nullbasic with endogenous DDX1 from cell lysates. BLI assays showed a direct interaction between Nullbasic and DDX1. Nullbasic affected DDX1 subcellular distribution in a Rev-independent manner. Interestingly overexpression of DDX1 in cells not only restored Rev-dependent mRNA export and gene expression in a Rev reporter assay but also partly reversed Nullbasic-induced Rev subcellular mislocalization. Moreover, HIV-1 wild type Tat co-immunoprecipitated with DDX1 and overexpression of Tat could rescue the unspliced viral mRNA levels inhibited by Nullbasic in HIV-1 expressing cells. CONCLUSIONS: Nullbasic was used to further define the complex mechanisms involved in the Rev-dependent nuclear export of the 9 kb and 4 kb viral RNAs. All together, these data indicate that DDX1 can be sequestered by Nullbasic leading to destabilization of the Rev nucleocytoplasmic transport complex and decreased levels of Rev-dependent viral transcripts. The outcomes support a role for DDX1 in maintenance of a Rev nuclear complex that transports viral RRE-containing mRNA to the cytoplasm. To our knowledge Nullbasic is the first anti-HIV protein that specifically targets the cellular protein DDX1 to block Rev’s activity. Furthermore, our research raises the possibility that wild type Tat may play a previously unrecognized but very important role in Rev function. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-014-0121-9) contains supplementary material, which is available to authorized users

Combination of searches for heavy spin-1 resonances using 139 fb−1 of proton-proton collision data at s = 13 TeV with the ATLAS detector

A combination of searches for new heavy spin-1 resonances decaying into different pairings of W, Z, or Higgs bosons, as well as directly into leptons or quarks, is presented. The data sample used corresponds to 139 fb−1 of proton-proton collisions at = 13 TeV collected during 2015–2018 with the ATLAS detector at the CERN Large Hadron Collider. Analyses selecting quark pairs (qq, bb, , and tb) or third-generation leptons (τν and ττ) are included in this kind of combination for the first time. A simplified model predicting a spin-1 heavy vector-boson triplet is used. Cross-section limits are set at the 95% confidence level and are compared with predictions for the benchmark model. These limits are also expressed in terms of constraints on couplings of the heavy vector-boson triplet to quarks, leptons, and the Higgs boson. The complementarity of the various analyses increases the sensitivity to new physics, and the resulting constraints are stronger than those from any individual analysis considered. The data exclude a heavy vector-boson triplet with mass below 5.8 TeV in a weakly coupled scenario, below 4.4 TeV in a strongly coupled scenario, and up to 1.5 TeV in the case of production via vector-boson fusion

Combined measurement of the Higgs boson mass from the H → γγ and H → ZZ∗ → 4ℓ decay channels with the ATLAS detector using √s = 7, 8, and 13 TeV pp collision data

A measurement of the mass of the Higgs boson combining the H → Z Z ∗ → 4 ℓ and H → γ γ decay channels is presented. The result is based on 140     fb − 1 of proton-proton collision data collected by the ATLAS detector during LHC run 2 at a center-of-mass energy of 13 TeV combined with the run 1 ATLAS mass measurement, performed at center-of-mass energies of 7 and 8 TeV, yielding a Higgs boson mass of 125.11 ± 0.09 ( stat ) ± 0.06 ( syst ) = 125.11 ± 0.11     GeV . This corresponds to a 0.09% precision achieved on this fundamental parameter of the Standard Model of particle physics

The effect of endwall manufacturing variations on turbine performance

Copyright © 2014 by ASME. Turbine blades and vanes of modern aero-engines are commonly manufactured by casting. The casting process often introduces slight geometry variations. In the endwall region this leads to inter-platform steps, gaps and leakage flows. This paper determines the underlying loss mechanisms associated with each of these geometric features and guides designers in minimizing their impact on efficiency. The paper shows that the presence of an inter-platform step causes a pair of vortical structures to be superimposed onto the blade existing secondary flow structure. These are shown to always increase loss. When manufacture variations are considered the optimal design intent blade is shown to be one where the suction side endwall is lower than the pressure side endwall. The paper shows that when leakage mass flow is introduced the presence of a step can either raise or reduce loss. A correlation which gives the optimal step height for a set leakage mass flow is presented. In the final part of the paper measured engine vane geometries are used to determine the impact of endwall geometry variation on turbine stage efficiency

Stall inception in low pressure ratio fans

A combined experimental and computational test programme, with two low pressure ratio aero-engine fans, has been used to identify the flow mechanisms at stall inception and the subsequent stall cell growth. The two fans have the same rotor tip clearance, annulus design and downstream stators, but different levels of tip loading. The measurement data show that both fans stall via spike-type inception, but that the growth of the stall cell, and the final cell size, is different in each fan. The computations, reproducing both the qualitative and quantitative behaviour of the steady-state and transient measurements, are used to identify the flow mechanisms at the origin of stall inception. In one fan, spillage of tip leakage flow upstream of the leading edge plane is responsible. In the other, sudden growth of casing corner separation blockage leads to stall. These two mechanisms are in accord with the findings from core compressors. However, the transonic aerodynamics and low hub-to-tip radius ratio of the fans leads to the following two findings: First, the casing corner separation is driven by shock-boundary layer interaction; second, the spanwise loading distribution of the fan determines whether the spike develops into full-span or part-span stall and both types of behaviour are represented in the present work. Finally, the axial momentum flux of the tip clearance flow is shown to be a useful indicator of the leakage jet spillage mechanism. A simple model is provided that links the tip loading, stagger and solidity with the tip clearance axial momentum flux, thereby allowing the aerodynamicist to connect, qualitatively, design parameters with the stall behaviour of the fan