Paving TRAIL's Path with Ubiquitin

Despite its name, signalling induced by the tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is versatile. Besides eliciting cell death by both apoptosis and necroptosis, TRAIL can also induce migration, proliferation, and cytokine production in cancerous and non-cancerous cells. Unravelling the mechanisms regulating the intricate balance between these different outputs could therefore facilitate our understanding of the role of TRAIL in tissue homeostasis, immunity, and cancer. Ubiquitination and its reversal, deubiquitination, are crucial modulators of immune receptor signalling. This review discusses recent progress on the orchestration of TRAIL signalling outcomes by ubiquitination of various components of the signalling complexes, our understanding of the molecular switches that decide between cell death and gene activation, and what remains to be discovered

Study of the microstructure resulting from brazed aluminium materials used in heat exchangers

Re-solidification of AA4343 cladding after brazing as well as the related precipitation in the modified AA3003 core material have been investigated. Analysis of the re-solidified material showed that partial dissolution of the core alloy occurs in both the brazing joints and away of them. Far from the brazing joints, the dissolution is, however, limited and diffusion of silicon from the liquid into the core material leads to solid-state precipitation in the so-called “band of dense precipitates” (BDP). On the contrary, the dissolution is enhanced in the brazing joint to such an extent that no BDP could be observed. The intermetallic phases present in the resolidified areas as well as in the core material have been analyzed and found to be mainly cubic alpha-Al(Mn,Fe)Si. These results were then compared to predictions made with available phase diagram information

Metric trees of generalized roundness one

Every finite metric tree has generalized roundness strictly greater than one. On the other hand, some countable metric trees have generalized roundness precisely one. The purpose of this paper is to identify some large classes of countable metric trees that have generalized roundness precisely one. At the outset we consider spherically symmetric trees endowed with the usual combinatorial metric (SSTs). Using a simple geometric argument we show how to determine decent upper bounds on the generalized roundness of finite SSTs that depend only on the downward degree sequence of the tree in question. By considering limits it follows that if the downward degree sequence $(d_{0}, d_{1}, d_{2}...)$ of a SST $(T,\rho)$ satisfies $|\{j \, | \, d_{j} > 1 \}| = \aleph_{0}$, then $(T,\rho)$ has generalized roundness one. Included among the trees that satisfy this condition are all complete $n$-ary trees of depth $\infty$ ($n \geq 2$), all $k$-regular trees ($k \geq 3$) and inductive limits of Cantor trees. The remainder of the paper deals with two classes of countable metric trees of generalized roundness one whose members are not, in general, spherically symmetric. The first such class of trees are merely required to spread out at a sufficient rate (with a restriction on the number of leaves) and the second such class of trees resemble infinite combs.Comment: 14 pages, 2 figures, 2 table

Insecurity for compact surfaces of positive genus

A pair of points in a riemannian manifold $M$ is secure if the geodesics between the points can be blocked by a finite number of point obstacles; otherwise the pair of points is insecure. A manifold is secure if all pairs of points in $M$ are secure. A manifold is insecure if there exists an insecure point pair, and totally insecure if all point pairs are insecure. Compact, flat manifolds are secure. A standing conjecture says that these are the only secure, compact riemannian manifolds. We prove this for surfaces of genus greater than zero. We also prove that a closed surface of genus greater than one with any riemannian metric and a closed surface of genus one with generic metric are totally insecure.Comment: 37 pages, 11 figure

A Detailed Analysis of the Dust Formation Zone of IRC+10216 Derived from Mid-IR Bands of C2H2 and HCN

A spectral survey of IRC+10216 has been carried out in the range 11 to 14 um with a spectral resolution of about 4 km s^-1. We have identified a forest of lines in six bands of C2H2 involving the vibrational states from the ground to 3nu5 and in two bands of HCN, involving the vibrational states from the ground up to 2nu2. Some of these transitions are observed also in H13CCH and H13CN. We have estimated the kinetic, vibrational, and rotational temperatures, and the abundances and column densities of C2H2 and HCN between 1 and 300 R* (1.5E16 cm) by fitting about 300 of these ro-vibrational lines. The envelope can be divided into three regions with approximate boundaries at 0.019 arcsec (the stellar photosphere), 0.1 arcsec (the inner dust formation zone), and 0.4 arcsec (outer dust formation zone). Most of the lines might require a large microturbulence broadening. The derived abundances of C2H2 and HCN increase by factors of 10 and 4, respectively, from the innermost envelope outwards. The derived column densities for both C2H2 and HCN are 1.6E19 cm^-2. Vibrational states up to 3000 K above ground are populated, suggesting pumping by near-infrared radiation from the star and innermost envelope. Low rotational levels can be considered under LTE while those with J>20-30 are not thermalized. A few lines require special analysis to deal with effects like overlap with lines of other molecules.Comment: 8 pages, 16 figures, 2 machine-readable tables, accepted in the Astrophysical Journa

Structured Operational Semantics for Graph Rewriting

Process calculi and graph transformation systems provide models of reactive systems with labelled transition semantics. While the semantics for process calculi is compositional, this is not the case for graph transformation systems, in general. Hence, the goal of this article is to obtain a compositional semantics for graph transformation system in analogy to the structural operational semantics (SOS) for Milner's Calculus of Communicating Systems (CCS). The paper introduces an SOS style axiomatization of the standard labelled transition semantics for graph transformation systems. The first result is its equivalence with the so-called Borrowed Context technique. Unfortunately, the axiomatization is not compositional in the expected manner as no rule captures "internal" communication of sub-systems. The main result states that such a rule is derivable if the given graph transformation system enjoys a certain property, which we call "complementarity of actions". Archetypal examples of such systems are interaction nets. We also discuss problems that arise if "complementarity of actions" is violated.Comment: In Proceedings ICE 2011, arXiv:1108.014

The linear ubiquitin chain assembly complex regulates TRAIL-induced gene activation and cell death.

The linear ubiquitin chain assembly complex (LUBAC) is the only known E3 ubiquitin ligase which catalyses the generation of linear ubiquitin linkages de novo LUBAC is a crucial component of various immune receptor signalling pathways. Here, we show that LUBAC forms part of the TRAIL-R-associated complex I as well as of the cytoplasmic TRAIL-induced complex II In both of these complexes, HOIP limits caspase-8 activity and, consequently, apoptosis whilst being itself cleaved in a caspase-8-dependent manner. Yet, by limiting the formation of a RIPK1/RIPK3/MLKL-containing complex, LUBAC also restricts TRAIL-induced necroptosis. We identify RIPK1 and caspase-8 as linearly ubiquitinated targets of LUBAC following TRAIL stimulation. Contrary to its role in preventing TRAIL-induced RIPK1-independent apoptosis, HOIP presence, but not its activity, is required for preventing necroptosis. By promoting recruitment of the IKK complex to complex I, LUBAC also promotes TRAIL-induced activation of NF-κB and, consequently, the production of cytokines, downstream of FADD, caspase-8 and cIAP1/2. Hence, LUBAC controls the TRAIL signalling outcome from complex I and II, two platforms which both trigger cell death and gene activation