directChillFoam: an OpenFOAM application for direct-chill casting

Direct-chill (DC) casting is a semi-continuous casting process that is used for producing aluminium and magnesium alloy billets (D. G. Eskin, 2008). As illustrated in (Figure 1), the process consists of feeding melt (liquid metal) into a mould containing a movable bottom (the ram). The ram is lowered and the billet is pulled downwards by gravity. As the billet exits the mould, its exposed outer surface is chilled with water jets to hasten cooling (hence the term direct-chill).Engineering and Physical Sciences Research Council (EPSRC), UK, under Grant Number EP/N007638/1, the UK Materials and Molecular Modelling Hub for computational resources, which is partially funded by EPSRC (EP/P020194/1 and EP/T022213/

Dynamics of two interacting hydrogen bubbles in liquid aluminium under the influence of a strong acoustic field

Ultrasonic melt processing significantly improves the properties of metallic materials. However, this promising technology has not been successfully transferred to the industry because of difficulties in treating large volumes of melt. To circumvent these difficulties, a fundamental understanding of the efficiency of ultrasonic treatment of liquid metals is required. In this endeavor, the dynamics of two interacting hydrogen bubbles in liquid aluminum are studied to determine the effect of a strong acoustic field on their behavior. It is shown that coalescence readily occurs at low frequencies in the range of 16 to 20 kHz; forcing frequencies at these values are likely to promote degassing. Emitted acoustic pressures from relatively isolated bubbles that resonate with the driving frequency are in the megapascal range and these cavitation shock waves are presumed to promote grain refinement by disrupting the growth of the solidification front

Magnetoresistance Effects in SrFeO(3-x): Dependence on Phase Composition and Relation to Magnetic and Charge Order

Single crystals of iron(IV) rich oxides SrFeO(3-x) with controlled oxygen content have been studied by Moessbauer spectroscopy, magnetometry, magnetotransport measurements, Raman spectroscopy, and infrared ellipsometry in order to relate the large magnetoresistance (MR) effects in this system to phase composition, magnetic and charge order. It is shown that three different types of MR effects occur. In cubic SrFeO3 (x = 0) a large negative MR of 25% at 9 T is associated with a hitherto unknown 60 K magnetic transition and a subsequent drop in resistivity. The 60 K transition appears in addition to the onset of helical ordering at ~130 K. In crystals with vacancy-ordered tetragonal SrFeO(3-x) as majority phase (x ~0.15) a coincident charge/antiferromagnetic ordering transition near 70 K gives rise to a negative giant MR effect of 90% at 9 T. A positive MR effect is observed in tetragonal and orthorhombic materials with increased oxygen deficiency (x = 0.19, 0.23) which are insulating at low temperatures. Phase mixtures can result in a complex superposition of these different MR phenomena. The MR effects in SrFeO(3-x) differ from those in manganites as no ferromagnetic states are involved

Fringe proteins modulate Notch-ligand cis and trans interactions to specify signaling states

The Notch signaling pathway consists of multiple types of receptors and ligands, whose interactions can be tuned by Fringe glycosyltransferases. A major challenge is to determine how these components control the specificity and directionality of Notch signaling in developmental contexts. Here, we analyzed same-cell (cis) Notch-ligand interactions for Notch1, Dll1, and Jag1, and their dependence on Fringe protein expression in mammalian cells. We found that Dll1 and Jag1 can cis-inhibit Notch1, and Fringe proteins modulate these interactions in a way that parallels their effects on trans interactions. Fringe similarly modulated Notch-ligand cis interactions during Drosophila development. Based on these and previously identified interactions, we show how the design of the Notch signaling pathway leads to a restricted repertoire of signaling states that promote heterotypic signaling between distinct cell types, providing insight into the design principles of the Notch signaling system, and the specific developmental process of Drosophila dorsal-ventral boundary formation

Comparison between low-order and high-order acoustic pressure solvers for bubbly media computations

Numerical modelling is a useful tool for the fundamental study of acoustic cavitation treatment in liquid metals. This treatment, also known as ultrasonic melt processing, significantly improves the properties and quality of metallic materials. However, the mechanisms leading to these observed improvements are still unclear and a fundamental study of cavitation treatment is required to understand this process. In this endeavour, this paper compares the use of high-order discretization schemes for solving acoustic pressures in cavitating liquids with its low-order counterpart. A fourth order scheme is shown to be more stable and accurate than a second order scheme when taking into account the acceleration of bubbles before their collapse, and is recommended for the full cavitation modelling of acoustic treatment of liquid metals.UK Engineering and Physical Sciences Research Council (EPSRC

Dynamic Ligand Discrimination in the Notch Signaling Pathway

The Notch signaling pathway comprises multiple ligands that are used in distinct biological contexts. In principle, different ligands could activate distinct target programs in signal-receiving cells, but it is unclear how such ligand discrimination could occur. Here, we show that cells use dynamics to discriminate signaling by the ligands Dll1 and Dll4 through the Notch1 receptor. Quantitative single-cell imaging revealed that Dll1 activates Notch1 in discrete, frequency-modulated pulses that specifically upregulate the Notch target gene Hes1. By contrast, Dll4 activates Notch1 in a sustained, amplitude-modulated manner that predominantly upregulates Hey1 and HeyL. Ectopic expression of Dll1 or Dll4 in chick neural crest produced opposite effects on myogenic differentiation, showing that ligand discrimination can occur in vivo. Finally, analysis of chimeric ligands suggests that ligand-receptor clustering underlies dynamic encoding of ligand identity. The ability of the pathway to utilize ligands as distinct communication channels has implications for diverse Notch-dependent processes

Universal Static and Dynamic Properties of the Structural Transition in Pb(Zn1/3Nb2/3)O3

The relaxors Pb(Zn$_{1/3}$Nb$_{2/3}$)O$_{3}$ (PZN) and Pb(Mg$_{1/3}$Nb$_{2/3}$)O$_{3}$ (PMN) have very similar properties based on the dielectric response around the critical temperature $T_{c}$ (defined by the structural transition under the application of an electric field). It has been widely believed that these materials are quite different below $T_{c}$ with the unit cell of PMN remaining cubic while in PZN the low temperature unit cell is rhombohedral in shape. However, this has been clarified by recent high-energy x-ray studies which have shown that PZN is rhombohedral only in the skin while the shape of the unit cell in the bulk is nearly cubic. In this study we have performed both neutron elastic and inelastic scattering to show that the temperature dependence of both the diffuse and phonon scattering in PZN and PMN is very similar. Both compounds show a nearly identical recovery of the soft optic mode and a broadening of the acoustic mode below $T_{c}$. The diffuse scattering in PZN is suggestive of an onset at the high temperature Burns temperature similar to that in PMN. In contrast to PMN, we observe a broadening of the Bragg peaks in both the longitudinal and transverse directions below $T_{c}$. We reconcile this additional broadening, not observed in PMN, in terms of structural inhomogeneity in PZN. Based on the strong similarities between PMN and PZN, we suggest that both materials belong to the same universality class and discuss the relaxor transition in terms of the three-dimensional Heisenberg model with cubic anisotropy in a random field.Comment: 11 pages, 10 figures. Updated version after helpful referee comment

4S-Hydroxylation of insulin at ProB28 accelerates hexamer dissociation and delays fibrillation

Daily injections of insulin provide lifesaving benefits to millions of diabetics. But currently available prandial insulins are suboptimal: The onset of action is delayed by slow dissociation of the insulin hexamer in the subcutaneous space, and insulin forms amyloid fibrils upon storage in solution. Here we show, through the use of non-canonical amino acid mutagenesis, that replacement of the proline residue at position 28 of the insulin B-chain (ProB28) by (4S)-hydroxyproline (Hzp) yields an active form of insulin that dissociates more rapidly, and fibrillates more slowly, than the wild-type protein. Crystal structures of dimeric and hexameric insulin preparations suggest that a hydrogen bond between the hydroxyl group of Hzp and a backbone amide carbonyl positioned across the dimer interface may be responsible for the altered behavior. The effects of hydroxylation are stereospecific; replacement of ProB28 by (4R)-hydroxyproline (Hyp) causes little change in the rates of fibrillation and hexamer disassociation. These results demonstrate a new approach that fuses the concepts of medicinal chemistry and protein design, and paves the way to further engineering of insulin and other therapeutic proteins

Ground State of Relaxor Ferroelectric Pb(Zn1/3Nb2/3)O3Pb(Zn_{1/3}Nb_{2/3})O_3

High energy x-ray diffraction measurements on Pb(Zn$_{1/3}$Nb$_{2/3}$)O$_3$ (PZN) single crystals show that the system does not have a rhombohedral symmetry at room temperature as previously believed. The new phase (X) in the bulk of the crystal gives Bragg peaks similar to that of a nearly cubic lattice with a slight tetragonal distortion. The Bragg profile remains sharp with no evidence of size broadening due to the polar micro crystals (MC). However, in our preliminary studies of the skin, we have found the expected rhombohedral (R) phase as a surface state. On the other hand, studies on an electric-field poled PZN single crystal clearly indicate a rhombohedral phase at room temperature.Comment: 11 pages with 3 figure

Cis-interactions between Notch and Delta generate mutually exclusive signalling states

The Notch–Delta signalling pathway allows communication between neighbouring cells during development^1. It has a critical role in the formation of ‘fine-grained’ patterns, generating distinct cell fates among groups of initially equivalent neighbouring cells and sharply delineating neighbouring regions in developing tissues. The Delta ligand has been shown to have two activities: it transactivates Notch in neighbouring cells and cis-inhibits Notch in its own cell. However, it remains unclear how Notch integrates these two activities and how the resulting system facilitates pattern formation. Here we report the development of a quantitative time-lapse microscopy platform for analysing Notch–Delta signalling dynamics in individual mammalian cells, with the aim of addressing these issues. By controlling both cis- and trans-Delta concentrations, and monitoring the dynamics of a Notch reporter, we measured the combined cis–trans input–output relationship in the Notch–Delta system. The data revealed a striking difference between the responses of Notch to trans- and cis-Delta: whereas the response to trans-Delta is graded, the response to cis-Delta is sharp and occurs at a fixed threshold, independent of trans-Delta. We developed a simple mathematical model that shows how these behaviours emerge from the mutual inactivation of Notch and Delta proteins in the same cell. This interaction generates an ultrasensitive switch between mutually exclusive sending (high Delta/low Notch) and receiving (high Notch/low Delta) signalling states. At the multicellular level, this switch can amplify small differences between neighbouring cells even without transcription-mediated feedback. This Notch–Delta signalling switch facilitates the formation of sharp boundaries and lateral-inhibition patterns in models of development, and provides insight into previously unexplained mutant behaviours