Influence of nozzle geometry on torch parameters during gas combustion

In this paper, when performing and analyzing the series of calculated results of the analysis of the sides of a rectangular nozzle for the parameters of a turbulent free air jet and a flame of a propane-butane mixture based on three-dimensional parabolic Navier-Stokes bonds for multicomponent reacting jets. To estimate the turbulent viscosity, differential equations of the kinetic and dissipation of the kinetic energy of turbulence are observed with refined empirical constants that are acceptable in turbulent combustion, as in the calculations, the initial values of the kinetic energy of turbulence did not exceed 5% of the dimensionless velocity of the main jet. It was found that when an air jet flows out of a nozzle with an aspect ratio of (1:2) and (1:4) in the initial sections of the jet, its shape behaves like an ellipse and, with the distance, it turns into a round one, with dimensionless, x greater or equal to 20 for the nozzle (1:2) and x greater or equal to 30 for (1:4), and for this variant there is again a transition to an elliptical shape. Studies of the diffusion combustion of a propane-butane mixture flowing out of a rectangular nozzle with an aspect ratio of (1:2) and (1:4) showed that with the ratio of the speed of the oxidizer to fuel mu, the flame length increases when mu between 0 and 0.164, and then, with an increase of mu more than 0.41, the torch length is shortened. The axial distributions of the momentum flux density with the aspect ratio (1:4), the jet core is shortened by 2÷2.5 times, compared with the aspect ratio (1:2) with the other parameters unchanged. Setting the tangential velocity at the mouth of the nozzle (ω=6.1 m/s) leads to a decrease in the torch length by 11% compared to its value equal to zero

A novel signalling screen demonstrates that CALR mutations activate essential MAPK signalling and facilitate megakaryocyte differentiation.

Most MPN patients lacking JAK2 mutations harbour somatic CALR mutations that are thought to activate cytokine signalling although the mechanism is unclear. To identify kinases important for survival of CALR-mutant cells we developed a novel strategy (KISMET) which utilises the full range of kinase selectivity data available from each inhibitor and thus takes advantage of off-target noise that limits conventional siRNA or inhibitor screens. KISMET successfully identified known essential kinases in haematopoietic and non-haematopoietic cell lines and identified the MAPK pathway as required for growth of the CALR-mutated MARIMO cells. Expression of mutant CALR in murine or human haematopoietic cell lines was accompanied by MPL-dependent activation of MAPK signalling, and MPN patients with CALR mutations showed increased MAPK activity in CD34-cells, platelets and megakaryocytes. Although CALR mutations resulted in protein instability and proteosomal degradation, mutant CALR was able to enhance megakaryopoiesis and pro-platelet production from human CD34+ progenitors. These data link aberrant MAPK activation to the MPN phenotype and identify it as a potential therapeutic target in CALR-mutant positive MPNs.Leukemia accepted article preview online, 14 October 2016. doi:10.1038/leu.2016.280.Work in the Green lab is supported by Leukemia and Lymphoma Research, Cancer Research UK, the NIHR Cambridge Biomedical Research Centre, the Cambridge Experimental Cancer Medicine Centre and the Leukemia & Lymphoma Society of America. WW is supported by the Austrian Science Foundation (J 3578-B21). CGA is supported by Kay Kendall Leukaemia Fund clinical research fellowship. UM is supported by a Cancer Research UK Clinician Scientist Fellowship. Work in the Huntly lab is supported by the European Research Council, the MRC (UK), Bloodwise, the Cambridge NIHR funded BRC, KKLF and a WT/MRC Stem Cell centre grant. Work in the Green and Huntly Labs is supported by core support grants by the Wellcome Trust to the Cambridge Institute for Medical Research (100140/z/12/z) and Wellcome Trust-MRC Cambridge Stem Cell Institute (097922/Z/11/Z)

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

FICD acts bifunctionally to AMPylate and de-AMPylate the endoplasmic reticulum chaperone BiP

Protein folding homeostasis in the endoplasmic reticulum (ER) is defended by an unfolded protein response that matches ER chaperone capacity to the burden of unfolded proteins. As levels of unfolded proteins decline, a metazoan-specific FIC-domain-containing ER-localized enzyme (FICD) rapidly inactivates the major ER chaperone BiP by AMPylating T518. Here we show that the single catalytic domain of FICD can also release the attached AMP, restoring functionality to BiP. Consistent with a role for endogenous FICD in de-AMPylating BiP, FICD$_{-/-}$ hamster cells are hypersensitive to introduction of a constitutively AMPylating, de-AMPylation-defective mutant FICD. These opposing activities hinge on a regulatory residue, E234, whose default state renders FICD a constitutive de-AMPylase $\textit{in vitro}$. The location of E234 on a conserved regulatory helix and the mutually antagonistic activities of FICD $\textit{in vivo}$, suggest a mechanism whereby fluctuating unfolded protein load actively switches FICD from a de-AMPylase to an AMPylase.Supported by Wellcome Trust Principal Research Fellowship to D.R. (Wellcome 200848/Z/16/Z), a UK Medical Research Council PhD studentship to L.A.P. and a Wellcome Trust Strategic Award to the Cambridge Institute for Medical Research (Wellcome 100140)