n/a

Prion protein (PrPC) biosynthesis involves a multi-step process that includes translation and post-translational modifications. While PrP has been widely investigated, for the homolog Doppel (Dpl), limited knowledge is available. In this study, we focused on a vital step of eukaryotic protein biosynthesis: targeting by the signal recognition particle (SRP). Taking the ovine Dpl (OvDpl(1-30)) peptide as a template, we studied its behavior in two different hydrophobic environments using CD and NMR spectroscopy. In both trifluoroethanol (TFE) and dihexanoyl-sn-glycero-3-phosphatidylcholine (DHPC), the OvDpl(1-30) peptide revealed to fold in an alpha-helical conformation with a well-defined central region extending from residue Cys8 until Ser22. The NMR structure was subsequently included in a computational docking complex with the conserved M-domain of SRP54 protein (SRP54M), and further compared with the N-terminal structures of mouse Dpl and bovine PrPC proteins. This allowed the determination of (i) common predicted N-terminal/SRP54M polar contacts (Asp331, Gln335, Glu365 and Lys432) and (ii) different N–C orientations between prion and Dpl peptides at the SRP54M hydrophobic groove, that are in agreement with each peptide electrostatic potential. Together, these findings provide new insights into the biosynthesis of prion-like proteins. Besides they also show the role of protein conformational switches in signalization toward the endoplasmic membrane, a key event of major significance in the cell cycle. They are thus of general applicability to the study of the biological function of prion-like as well as other proteins.

The paper analyses numerical solutions for the process leading to debonding failure of fiber reinforced polymers (FRP)-to-concrete interfaces in shear tests with the FRP plate subjected to a tensile load at one end. Any realistic local nonlinear bond-slip law can be used in the numerical analysis proposed in the present study. However, only a Popovics’ type expression is employed in the numerical process due to its use in different studies found in the literature. Effective bond length (Leff) is discussed and an expression depending on the Popovics’ constant (nP) is proposed to calculate it. Assuming a fracture in pure Mode II, the debonding process is analyzed in detail and distributions of bond stresses and strains in the FRP plate along the interface are presented. The load-displacement behaviour is also presented and the influence of the local bond-slip law on the debonding process is discussed.

n/a

n/a

This paper is discussing the intuitive interaction with robotic systems and the conceptualisation connected with known organisational problems. In particular, the focus will be on the manufacturing industry with respect to its social dimension. One of the aims is to identify relevant research questions about the possibility of development of safer robot systems in closer human-machine intuitive interaction systems at the manufacturing shop-floor level. We try to contribute to minimize the cognitive and perceptual workload for robot operators in complex working systems. In particular that will be highly relevant when more different robots with different roles and produced by different companies or designers are to be used in the manufacturing industry to a larger extent. The social sciences approach to such technology assessment is of high relevance to understand the dimensions of the intuitive interaction concept.

Titanosauriforms represent a diverse and globally distributed clade of neosauropod dinosaurs, but their inter-relationships remain poorly understood. Here we redescribe Lusotitan atalaiensis from the Late Jurassic Lourinhã Formation of Portugal, a taxon previously referred to Brachiosaurus. The lectotype includes cervical, dorsal, and caudal vertebrae, and elements from the forelimb, hindlimb, and pelvic girdle. Lusotitan is a valid taxon and can be diagnosed by six autapomorphies, including the presence of elongate postzygapophyses that project well beyond the posterior margin of the neural arch in anterior-to-middle caudal vertebrae. A new phylogenetic analysis, focused on elucidating the evolutionary relationships of basal titanosauriforms, is presented, comprising 63 taxa scored for 279 characters. Many of these characters are heavily revised or novel to our study, and a number of ingroup taxa have never previously been incorporated into a phylogenetic analysis. We treated quantitative characters as discrete and continuous data in two parallel analyses, and explored the effect of implied weighting. Although we recovered monophyletic brachiosaurid and somphospondylan sister clades within Titanosauriformes, their compositions were affected by alternative treatments of quantitative data and, especially, by the weighting of such data. This suggests that the treatment of quantitative data is important and the wrong decisions might lead to incorrect tree topologies. In particular, the diversity of Titanosauria was greatly increased by the use of implied weights. Our results support the generic separation of the contemporaneous taxa Brachiosaurus, Giraffatitan, and Lusotitan, with the latter recovered as either a brachiosaurid or the sister taxon to Titanosauriformes. Although Janenschia was recovered as a basal macronarian, outside Titanosauria, the sympatric Australodocus provides body fossil evidence for the pre-Cretaceous origin of titanosaurs. We recovered evidence for a sauropod with close affinities to the Chinese taxon Mamenchisaurus in the Late Jurassic Tendaguru beds of Africa, and present new information demonstrating the wider distribution of caudal pneumaticity within Titanosauria. The earliest known titanosauriform body fossils are from the late Oxfordian (Late Jurassic), although trackway evidence indicates a Middle Jurassic origin. Diversity increased throughout the Late Jurassic, and titanosauriforms did not undergo a severe extinction across the Jurassic/Cretaceous boundary, in contrast to diplodocids and non-neosauropods. Titanosauriform diversity increased in the Barremian and Aptian–Albian as a result of radiations of derived somphospondylans and lithostrotians, respectively, but there was a severe drop (up to 40%) in species numbers at, or near, the Albian/Cenomanian boundary, representing a faunal turnover whereby basal titanosauriforms were replaced by derived titanosaurs, although this transition occurred in a spatiotemporally staggered fashion.

This research has been motivated by a real-life problem of a waste cooking oil collection system characterized by the existence of multiple depots with an outsourced vehicle fleet, where the collection routes have to be plan. The routing problem addressed allows open routes between depots, i.e., all routes start at one depot but can end at the same or at a different one, depending on what minimizes the objective function considered. Such problem is referred as a Multi-Depot Vehicle Routing Problem with Mixed Closed and Open Inter-Depot Routes and is, in this paper, modeled through a Mixed Integer Linear Programming (MILP) formulation where capacity and duration constraints are taken into account. The model developed is applied to the real case study providing, as final results, the vehicle routes planning where a decrease of 13% on mileage and 11% on fleet hiring cost are achieved, when comparing with the current company solution.

The preferential binding of anions and cations in aqueous solutions of the ionic liquids (ILs) 1-butyl- 3-methylimidazolium ([C₄mim]⁺) and 1-ethyl-3-methylimidazolium ([C₂mim]⁺) chloride and dicyanamide (dca^-) with the small alpha-helical protein Im7 was investigated using a combination of differential scanning calorimetry, NMR spectroscopy and molecular dynamics (MD) simulations. Our results show that direct ion interactions are crucial to understand the effects of ILs on the stability of proteins and that an anion effect is dominant. We show that the binding of weakly hydrated anions to positively charged or polar residues leads to the partial dehydration of the backbone groups, and is critical to control stability, explaining why dca^- is more denaturing than Cl^-. Direct cation–protein interactions also mediate stability; cation size and hydrophobicity are relevant to account for destabilisation as shown by the effect of [C₄mim]⁺ compared to [C₂mim]⁺. The specificity in the interaction of IL ions with protein residues established by weak favourable interactions is confirmed by NMR chemical shift perturbation, amide hydrogen exchange data and MD simulations. Differences in specificity are due to the balance of interaction established between ion pairs and ion-solvent that determine the type of residues affected. When the interaction of both cation and anion with the protein is strong the net result is similar to a non-specific interaction, leading ultimately to unfolding. Since the nature of the ions is a determinant of the level of interaction with the protein towards denaturation or stabilisation, ILs offer a unique possibility to modulate protein stabilisation or even folding events.

Let \(\mathcal{M}(\mathbb{R}^n)\) be the class of bounded away from one and infinity functions \(p:\mathbb{R}^n\to[1,\infty]\) such that the Hardy-Littlewood maximal operator is bounded on the variable Lebesgue space \(L^{p(\cdot)}(\mathbb{R}^n)\). We show that if \(a\) belongs to the Hörmander class \(S_{\rho,\delta}^{n(\rho-1)}\) with \(0<\rho\le 1\), \(0\le\delta<1\), then the pseudodifferential operator \(\operatorname{Op}(a)\) is bounded on the variable Lebesgue space \(L^{p(\cdot)}(\mathbb{R}^n)\) provided that \(p\in\mathcal{M}(\mathbb{R}^n)\). Let \(\mathcal{M}^*(\mathbb{R}^n)\) be the class of variable exponents \(p\in\mathcal{M}(\mathbb{R}^n)\) represented as \(1/p(x)=\theta/p_0+(1-\theta)/p_1(x)\) where \(p_0\in(1,\infty)\), \(\theta\in(0,1)\), and \(p_1\in\mathcal{M}(\mathbb{R}^n)\). We prove that if \(a\in S_{1,0}^0\) slowly oscillates at infinity in the first variable, then the condition \[ \lim_{R\to\infty}\inf_{|x|+|\xi|\ge R}|a(x,\xi)|>0 \] is sufficient for the Fredholmness of \(\operatorname{Op}(a)\) on \(L^{p(\cdot)}(\mathbb{R}^n)\) whenever \(p\in\mathcal{M}^*(\mathbb{R}^n)\). Both theorems generalize pioneering results by Rabinovich and Samko [RS08] obtained for globally log-Hölder continuous exponents \(p\), constituting a proper subset of \(\mathcal{M}^*(\mathbb{R}^n)\).

n/a

n/a

n/a