Fundamental Studies on the Use of Distributed Fibre Optical Sensing on Concrete and Reinforcing Bars

Distributed fibre optical sensing (DFOS) allows for quasi-continuous strain measurement in a broad range of gauge lengths and measurement frequencies. In particular, Rayleigh backscatter-based coherent optical frequency domain reflectometry has recently registered a significant application increase in structural concrete research and monitoring thanks to its numerous merits, such as high resolution and low invasiveness. However, it is not a plug-and-play technique. The quality of the acquired data depends highly on the choice of the fibre optical sensor and the methods of instrumentation and post-processing. Furthermore, its unprecedented resolution and sensitivity allow capturing local effects not well documented so far. This paper analyses the suitability of DFOS based on Rayleigh backscatter for reliably measuring strains and discusses the origin and structural relevance of local variations in the results. A series of experimental investigations are presented, comprising tensile tests on bare reinforcing bars and concrete compression tests. A critical analysis of the results leads to a best practice for applying DFOS to reinforcing bars and concrete, which establishes a basis for reliable, accurate measurements in structural concrete applications with bonded reinforcement.

Design rules for timber log reciprocal floors, based on mass optimization under stiffness constraint

Building with raw timber allows to reduce the price of construction and to make it more competitive with respect to concrete or steel construction. For a few years now, the combination of parametric design and robotic tools make possible the fast and precise milling of timber logs for their accurate connection. However, the spans are quickly limited by the logs length. In this context, reciprocal structures are relevant, since they allow to build large spans structures with short beams. Finally, the architectural interest of reciprocal structures is not to prove. However, the choice of the most efficient reciprocal frame, as well as its structural relevance in terms of mass and stiffness is, most of the time, ruled by subjective considerations. This paper focuses on rectangular floors composed of reciprocal moduli and has three objectives: (1) to develop a general mass and stiffness optimization method for reciprocal floors, which is not only necessary to limit the price, but also to reduce their thickness, (2) to define design rules for reciprocal floors, in particular for the choice of the best engagement ratio, and (3) to compare the structural efficiency of reciprocal floors with the one of “traditional” floors with parallel logs. Coming from a dimensionless transformation of the equilibrium equations, the results of this article will thus give the designers keys to better design reciprocal structures, evaluate their structural performances and relevance, and justify their choices.

An electrostatics method for converting a time-series into a weighted complex network

This paper proposes a new method for converting a time-series into a weighted graph (complex network), which builds on electrostatics in physics. The proposed method conceptualizes a time-series as a series of stationary, electrically charged particles, on which Coulomb-like forces can be computed. This allows generating electrostatic-like graphs associated with time-series that, additionally to the existing transformations, can be also weighted and sometimes disconnected. Within this context, this paper examines the structural similarity between five different types of time-series and their associated graphs that are generated by the proposed algorithm and the visibility graph, which is currently the most popular algorithm in the literature. The analysis compares the source (original) time-series with the node-series generated by network measures (that are arranged into the node-ordering of the source time-series), in terms of a linear trend, chaotic behaviour, stationarity, periodicity, and cyclical structure. It is shown that the proposed electrostatic graph algorithm generates graphs with node-measures that are more representative of the structure of the source time-series than the visibility graph. This makes the proposed algorithm more natural rather than algebraic, in comparison with existing physics-defined methods. The overall approach also suggests a methodological framework for evaluating the structural relevance between the source time-series and their associated graphs produced by any possible transformation.

Structure and function at the lipid–protein interface of a pentameric ligand-gated ion channel

Although it has long been proposed that membrane proteins may contain tightly bound lipids, their identity, the structure of their binding sites, and their functional and structural relevance have remained elusive. To some extent, this is because tightly bound lipids are often located at the periphery of proteins, where the quality of density maps is usually poorer, and because they may be outcompeted by detergent molecules used during standard purification procedures. As a step toward characterizing natively bound lipids in the superfamily of pentameric ligand-gated ion channels (pLGICs), we applied single-particle cryogenic electron microscopy to fragments of native membrane obtained in the complete absence of detergent-solubilization steps. Because of the heterogeneous lipid composition of membranes in the secretory pathway of eukaryotic cells, we chose to study a bacterial pLGIC (ELIC) expressed in Escherichia coli’s inner membrane. We obtained a three-dimensional reconstruction of unliganded ELIC (2.5-Å resolution) that shows clear evidence for two types of tightly bound lipid at the protein–bulk-membrane interface. One of them was consistent with a “regular” diacylated phospholipid, in the cytoplasmic leaflet, whereas the other one was consistent with the tetra-acylated structure of cardiolipin, in the periplasmic leaflet. Upon reconstitution in E. coli polar-lipid bilayers, ELIC retained the functional properties characteristic of members of this superfamily, and thus, the fitted atomic model is expected to represent the (long-debated) unliganded-closed, “resting” conformation of this ion channel. Notably, the addition of cardiolipin to phosphatidylcholine membranes restored the ion-channel activity that is largely lost in phosphatidylcholine-only bilayers.

Characterization of the Structural Determinants of the Ubiquitin-Dependent Proteasomal Degradation of Human Hepatic Tryptophan 2,3-Dioxygenase

Human hepatic tryptophan 2,3-dioxygenase (hTDO) is a homotetrameric hemoprotein. It is one of the most rapidly degraded liver proteins with a half-life (t1/2) of ~2.3 h, relative to an average t1/2 of ~2–3 days for total liver protein. The molecular mechanism underlying the poor longevity of hTDO remains elusive. Previously, we showed that hTDO could be recognized and ubiquitinated by two E3 ubiquitin (Ub) ligases, gp78/AMFR and CHIP, and subsequently degraded via Ub-dependent proteasomal degradation (UPD) pathway. Additionally, we identified 15 ubiquitination K sites and demonstrated that Trp-binding to an exosite impeded its proteolytic degradation. Here we further established autophagic lysosomal degradation (ALD) as an alternative back-up pathway for cellular hTDO degradation. In addition, with protein kinases A and C, we identified 13 phosphorylated Ser/Thr (pS/pT) sites. Mapping these pS/pT sites on the hTDO surface revealed their propinquity to acidic Asp/Glu (D/E) residues engendering negatively charged DEpSpT clusters vicinal to the ubiquitination K sites over the entire protein surface. Through site-directed mutagenesis of positively charged patches of gp78, previously documented to interact with the DEpSpT clusters in other target proteins, we uncovered the likely role of the DEpSpT clusters in the molecular recognition of hTDO by gp78 and plausibly other E3 Ub-ligases. Furthermore, cycloheximide-chase analyses revealed the critical structural relevance of the disordered N- and C-termini not only in the Ub-ligase recognition, but also in the proteasome engagement. Together, the surface DEpSpT clusters and the N- and C-termini constitute an intrinsic bipartite degron for hTDO physiological turnover.

Norditerpenoid alkaloids from Aconitum and Delphinium: structural relevance in medicine, toxicology, and metabolism

This highlight focuses on norditerpenoid alkaloids from Aconitum and Delphinium where their structural differences result in pharmacological diversity that ranges from poisons to drugs.

StructureDistiller: Structural relevance scoring identifies the most informative entries of a contact map

Protein folding and structure prediction are two sides of the same coin. Contact maps and the related techniques of constraint-based structure reconstruction can be considered as unifying aspects of both processes. We present the Structural Relevance (SR) score which quantifies the information content of individual contacts and residues in the context of the whole native structure. The physical process of protein folding is commonly characterized with spatial and temporal resolution: some residues are Early Folding while others are Highly Stable with respect to unfolding events. We employ the proposed SR score to demonstrate that folding initiation and structure stabilization are subprocesses realized by distinct sets of residues. The example of cytochrome c is used to demonstrate how StructureDistiller identifies the most important contacts needed for correct protein folding. This shows that entries of a contact map are not equally relevant for structural integrity. The proposed StructureDistiller algorithm identifies contacts with the highest information content; these entries convey unique constraints not captured by other contacts. Identification of the most informative contacts effectively doubles resilience toward contacts which are not observed in the native contact map. Furthermore, this knowledge increases reconstruction fidelity on sparse contact maps significantly by 0.4 Å.

StructureDistiller: Structural relevance scoring increases resilience of contact maps to false positive predictions

Protein folding and structure prediction are two sides of the same coin. We propose contact maps and the related techniques of constraint-based structure reconstruction as unifying aspect of both processes. The presented Structural Relevance (SR) score quantifies the contribution of individual contacts and residues to structural integrity.It is demonstrated that entries of a contact map are not equally relevant for structural integrity. Structure prediction methods should explicitly consider the most relevant contacts for optimal performance because they effectively double resilience toward false positively predicted contacts. Furthermore, knowledge of the most relevant contacts significantly increases reconstruction fidelity on sparse contact maps by 0.4 Å.Protein folding is commonly characterized with spatial and temporal resolution: some residues are Early Folding while others are Highly Stable with respect to unfolding events. Using the proposed SR score, we demonstrate that folding initiation and structure stabilization are distinct processes.