Rapid degradation of mutant SLC25A46 by the ubiquitin-proteasome system results in MFN1/2-mediated hyperfusion of mitochondria.

SCL25A46 is a mitochondrial carrier protein that surprisingly localizes to the outer membrane and is distantly related to Ugo1. Here we show that a subset of SLC25A46 interacts with mitochondrial dynamics components and the MICOS complex. Decreased expression of SLC25A46 results in increased stability and oligomerization of MFN1 and MFN2 on mitochondria, promoting mitochondrial hyperfusion. A mutation at L341P causes rapid degradation of SLC25A46, which manifests as a rare disease, pontocerebellar hypoplasia. The E3 ubiquitin ligases MULAN and MARCH5 coordinate ubiquitylation of SLC25A46 L341P, leading to degradation by organized activities of P97 and the proteasome. Whereas outer mitochondrial membrane-associated degradation is typically associated with apoptosis or a specialized type of autophagy termed mitophagy, SLC25A46 degradation operates independently of activation of outer membrane stress pathways. Thus SLC25A46 is a new component in mitochondrial dynamics that serves as a regulator for MFN1/2 oligomerization. Moreover, SLC25A46 is selectively degraded from the outer membrane independently of mitophagy and apoptosis, providing a framework for mechanistic studies in the proteolysis of outer membrane proteins

Experimental and numerical prediction of extrusion load at different lubricating conditions of aluminium 6063 alloy in backward cup extrusion

In the present research work using a backward cup extrusion (BCE) die profile, different lubricating conditions on aluminum alloy AA6063 have been experimentally and numerically investigated to predict the extrusion load. It was obvious that due to an increase in applications of the extrusion process, many researchers have worked on the extrusion process using different methods to achieve their aims. This experiment was conducted with three different lubricants namely: Castor oil, Palm Oil and tropical coconut oil; as well as without lubricants. Different lubricating conditions were employed of varying strain rates ranges from 1.5×10-3s-1, 2.0×10-3s-1, 2.5×10-3s-1, and 3.0×10-3s-1; Numerical analysis and simulation for dry and lubricated conditions during extrusion load were also performed using DEFORM 3D software. The results show that prediction extrusion load increases with increasing strain rates. The maximum extrusion load was found to be higher for extrusion without lubricants. In all cases of strain rate, palm oil showed a lower extrusion load compared to the other lubricants. Castor oil indicated the highest extrusion load when the experiment was carried out using lubrication. There was a consistent agreement between the result gotten from the experiment and simulation results of the extrusion load-strike curve.Peer reviewedFinal Published versio

Numerical Implementation of lepton-nucleus interactions and its effect on neutrino oscillation analysis

We discuss the implementation of the nuclear model based on realistic nuclear spectral functions in the GENIE neutrino interaction generator. Besides improving on the Fermi gas description of the nuclear ground state, our scheme involves a new prescription for $Q^2$ selection, meant to efficiently enforce energy momentum conservation. The results of our simulations, validated through comparison to electron scattering data, have been obtained for a variety of target nuclei, ranging from carbon to argon, and cover the kinematical region in which quasi elastic scattering is the dominant reaction mechanism. We also analyse the influence of the adopted nuclear model on the determination of neutrino oscillation parameters.Comment: 19 pages, 35 figures, version accepted by Phys. Rev.

Positive-P phase space method simulation in superradiant emission from a cascade atomic ensemble

The superradiant emission properties from an atomic ensemble with cascade level configuration is numerically simulated. The correlated spontaneous emissions (signal then idler fields) are purely stochastic processes which are initiated by quantum fluctuations. We utilize the positive-P phase space method to investigate the dynamics of the atoms and counter-propagating emissions. The light field intensities are calculated, and the signal-idler correlation function is studied for different optical depths of the atomic ensemble. Shorter correlation time scale for a denser atomic ensemble implies a broader spectral window needed to store or retrieve the idler pulse.Comment: To be published in Phys. Rev.

Enantioselective Organocatalytic Intramolecular Diels−Alder Reactions. The Asymmetric Synthesis of Solanapyrone D

The first direct enantioselective organocatalytic intramolecular Diels−Alder reaction has been accomplished. The use of iminium catalysis has provided a new catalytic strategy for the enantioselective [4 + 2] cycloisomerization of a wide variety of tethered diene-enal systems. The use of imidazolidinones 1 and 2 as the asymmetric catalysts has been found to mediate the enantioselective construction of [4.4.0] and [4.3.0] ring systems. Application of this methodology to the highly efficient asymmetric synthesis of the marine metabolite solanpyrone D has also been accomplished. A diverse spectrum of aldehyde substrates can also be accommodated in this new organocatalytic transformation. Importantly, this technology has been utilized to execute the first enantioselective, catalytic Type II IMDA reaction

Real-time diagnostics of gas/water assisted injection moulding using integrated ultrasonic sensors

YesAn ultrasound sensor system has been applied to the mould of both the water and gas assisted injection moulding processes. The mould has a cavity wall mounted pressure sensor and instrumentation to monitor the injection moulding machine. Two ultrasound sensors are used to monitor the arrival of the fluid (gas or water) bubble tip through the detection of reflected ultrasound energy from the fluid polymer boundary and the fluid bubble tip velocity through the polymer melt is estimated. The polymer contact with the cavity wall is observed through the reflected ultrasound energy from that boundary. A theoretically based estimation of the residual wall thickness is made using the ultrasound reflection from the fluid (gas or water) polymer boundary whilst the samples are still inside the mould and a good correlation with a physical measurement is observed

Preparation for Scaling Studies of Ice-Crystal Icing at the NRC Research Altitude Test Facility

This paper describes experiments conducted at the National Research Council (NRC) of Canadas Research Altitiude Test Facility between March 26 and April 11, 2012. The tests, conducted collaboratively between NASA and NRC, focus on three key aspects in preparation for later scaling work to be conducted with a NACA 0012 airfoil model in the NRC Cascade rig: (1) cloud characterization, (2) scaling model development, and (3) ice-shape profile measurements. Regarding cloud characterization, the experiments focus on particle spectra measurements using two shadowgraphy methods, cloud uniformity via particle scattering from a laser sheet, and characterization of the SEA Multi-Element probe. Overviews of each aspect as well as detailed information on the diagnostic method are presented. Select results from the measurements and interpretation are presented which will help guide future work