Non-steroidal anti-inflammatory drugs exert their pharmacological activity through inhibition of cyclooxygenase 1 and 2 (COX-1 and COX-2). Recent research suggests that a balanced inhibition of both COX-1 and COX-2 is the key to reduce the side-effects exhibited by COX inhibitors. We developed new benzimidazole-based compounds that showed a balanced COX inhibition, supported by molecular docking screening. The human whole blood assays demonstrated that the ester derivatives were potent inhibitors. Competitive saturation transfer difference (STD)-NMR experiments, in the presence of COX-2, using naproxen and diclofenac demonstrated that ester derivatives do not compete with diclofenac for the same binding site, but compete with the allosteric inhibitor naproxen. Combination of NMR spectroscopy with molecular docking has permitted us to detect a new naproxen-like inhibitor, which could be used for future drug development.

In Late Triassic (Norian–Rhaetian) times, the Jameson Land Basin lay at 40° N on the northern part of the supercontinent Pangaea. This position placed the basin in a transition zone between the relatively dry interior of the supercontinent and its more humid periphery. Sedimentation in the Jameson Land Basin took place in a lake–mudflat system and was controlled by orbitally forced variations in precipitation. Vertebrate fossils have consistently been found in these lake deposits (Fleming Fjord Formation), and include fishes, dinosaurs, amphibians, turtles, aetosaurs and pterosaurs. Furthermore, the fauna includes mammaliaform teeth and skeletal material. New vertebrate fossils were found during a joint vertebrate palaeontological and sedimentological expedition to Jameson Land in 2012. These new finds include phytosaurs, a second stem testudinatan specimen and new material of sauropodomorph dinosaurs, including osteologically immature individuals. Phytosaurs are a group of predators common in the Late Triassic, but previously unreported from Greenland. The finding includes well-preserved partial skeletons that show the occurrence of four individuals of three size classes. The new finds support a late Norian–early Rhaetian age for the Fleming Fjord Formation, and add new information on the palaeogeographical and palaeolatitudinal distribution of Late Triassic faunal provinces.

The Ørsted Dal Member of the Upper Triassic Fleming Fjord Formation in East Greenland is well known for its rich vertebrate fauna, represented by numerous specimens of both body and ichnofossils. In particular, the footprints of theropod dinosaurs have been described. Recently, an international expedition discovered several slabs with 100 small chirotheriid pes and manus imprints (pes length 4–4.5 cm) in siliciclastic deposits of this unit. They show strong similarities with Brachychirotherium, a characteristic Upper Triassic ichnogenus with a global distribution. A peculiar feature in the Fleming Fjord specimens is the lack of a fifth digit, even in more deeply impressed imprints. Therefore, the specimens are assigned here tentatively to cf. Brachychirotherium. Possibly, this characteristic is related to the extremely small size and early ontogenetic stage of the trackmaker. The record from Greenland is the first evidence of this morphotype from the Fleming Fjord Formation. Candidate trackmakers are crocodylian stem group archosaurs; however, a distinct correlation with known osteological taxa from this unit is not currently possible. While the occurrence of sauropodomorph plateosaurs in the bone record links the Greenland assemblage more closer to that from the Germanic Basin of central Europe, here the described footprints suggest a Pangaea-wide exchange.Supplementary material: Three-dimensional model of cf. Brachychirotherium pes–manus set (from MGUH 31233b) from the Upper Triassic Fleming Fjord Formation (Norian–Rhaetian) of East Greenland as pdf, ply and jpg files (3D model created by Oliver Wings; photographs taken by Jesper Milàn) is available at https://doi.org/10.6084/m9.figshare.c.2133546

A large collection of vertebrate coprolites from black lacustrine shales in the Late Triassic (Rhaetian–Sinemurian) Kap Stewart Formation, East Greenland is examined with regard to internal and external morphology, prey inclusions, and possible relationships to the contemporary vertebrate fauna. A number of the coprolites were mineralogically examined by X-ray diffraction (XRD), showing the primary mineral composition to be apatite, clay minerals, carbonates and, occasionally, quartz in the form of secondary mineral grains. The coprolite assemblage shows multiple sizes and morphotypes of coprolites, and different types of prey inclusions, demonstrating that the coprolite assemblage originates from a variety of different producers.Supplementary material: A description of the size, shape, structure, texture, contents and preservation of the 328 specimens is available at https://doi.org/10.6084/m9.figshare.c.2134335

Abstract The strain rate dependent mechanical behaviour was studied for the common out-of-autoclave aerospace textile composite 5-harness-satin carbon–epoxy. End-loaded 15 ° , 30 ° and 45 ° off-axis and 90 ° compression tests were carried out at three different strain rate levels ( 4 × 10 - 4 s - 1 , 200 s - 1 and 1000 s - 1 ) to determine the effect of strain rate for transverse compression and combined transverse compression/in-plane shear loading. The dynamic tests were carried out on a split-Hopkinson pressure bar, where high speed photography and digital image correlation allowed a detailed study of the specimen deformation and failure process. Quasi-static reference tests were carried out on an electro-mechanical test machine using the same specimen type and a static \{DIC\} system. Pronounced strain rate effects on the axial stress–strain response were observed for all specimen types. Failure envelopes for the combined σ 22 c - τ 12 stress state were derived from the experimental data and compared with the maximum stress criterion, which appears well suited to approximate the experimental failure envelope at all strain rate levels. It was observed that the failure envelope was simply scaled up with increasing strain rate, while the overall shape was found to be strain rate independent.

Nucleation is a critical step determining the outcome of the entire crystallization process. Finding an effective nucleant for protein crystallization is of utmost importance for structural biology. The latter relies on good-quality crystals to solve the three-dimensional structures of macromolecules. In this study we show that crystalline barium sulfate (BaSO4) with an etched and/or ionic liquid (IL)-functionalized surface (1) can induce protein nucleation at concentrations well below the concentration needed to promote crystal growth under control conditions, (2) can shorten the nucleation time, (3) can increase the growth rate, and finally (4) may help to improve the protein crystal morphology. These effects were shown for lysozyme, RNase A, trypsin, proteinase K, myoglobin, and hemoglobin. Therefore, the use of BaSO4 particles enables us to reduce the amount of protein in crystallization trials and increases the chance of obtaining protein crystals of the desired quality. In the context of the underlying mechanism, it is shown that the protein-solid contact formation is governed by the interaction of the polar compartments of the biomacromolecule with the support. The tendency of a protein to concentrate near the solid surface is enhanced by both the hydrophobicity of the protein and that of the surface (tuned by the functionalizing IL). These mechanisms of interaction of biomacromolecules with inorganic hydrophilic solids correspond to the principles of amphiphilic IL-mineral interactions.

In Late Triassic (Norian–Rhaetian) times, the Jameson Land Basin lay at 40° N on the northern part of the supercontinent Pangaea. This position placed the basin in a transition zone between the relatively dry interior of the supercontinent and its more humid periphery. Sedimentation in the Jameson Land Basin took place in a lake–mudflat system and was controlled by orbitally forced variations in precipitation. Vertebrate fossils have consistently been found in these lake deposits (Fleming Fjord Formation), and include fishes, dinosaurs, amphibians, turtles, aetosaurs and pterosaurs. Furthermore, the fauna includes mammaliaform teeth and skeletal material. New vertebrate fossils were found during a joint vertebrate palaeontological and sedimentological expedition to Jameson Land in 2012. These new finds include phytosaurs, a second stem testudinatan specimen and new material of sauropodomorph dinosaurs, including osteologically immature individuals. Phytosaurs are a group of predators common in the Late Triassic, but previously unreported from Greenland. The finding includes well-preserved partial skeletons that show the occurrence of four individuals of three size classes. The new finds support a late Norian–early Rhaetian age for the Fleming Fjord Formation, and add new information on the palaeogeographical and palaeolatitudinal distribution of Late Triassic faunal provinces.

In 1994 fib Commission 6: Prefabrication edited a successful Planning and Design Handbook that ran to approximately 45,000 copies and was published in Spanish and German.Nearly 20 years later Bulletin 74 brings that first publication up to date. It offers a synthesis of the latest structural design knowledge about precast building structures against the background of 21st century technological innovations in materials, production and construction. With it, we hope to help architects and engineers achieve a full understanding of precast concrete building structures, the possibilities they offer and their specific design philosophy. It was principally written for non-seismic structures.

The handbook contains eleven chapters, each dealing with a specific aspect of precast building structures.
The first chapter of the handbook highlights best practice opportunities that will enable architects, design engineers and contractors to work together towards finding efficient solutions, which is something unique to precast concrete buildings.
The second chapter offers basic design recommendations that take into account the possibilities, restrictions and advantages of precast concrete, along with its detailing, manufacture, transport, erection and serviceability stages.
Chapter three describes the precast solutions for the most common types of buildings such as offices, sports stadiums, residential buildings, hotels, industrial warehouses and car parks. Different application possibilities are explored to teach us which types of precast units are commonly used in all those situations.
Chapter four covers the basic design principles and systems related to stability. Precast concrete structures should be designed according to a specific stability concept, unlike cast in-situ structures.
Chapter five discusses structural connections.
Chapters six to nine address the four most commonly used systems or subsystems of precast concrete in buildings, namely, portal and skeletal structures, wall-frame structures, floor and roof structures and architectural concrete facades.
In chapter ten the design and detailing of a number of specific construction details in precast elements are discussed, for example, supports, corbels, openings and cutouts in the units, special features related to the detailing of the reinforcement, and so forth.
Chapter eleven gives guidelines for the fire design of precast concrete structures. The handbook concludes with a list of references to good literature on precast concrete construction.

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Motivated by the need to describe bear-bull market regime switching in stock prices, we introduce and study a stochastic process in continuous time with two regimes, threshold and delay, given by a stochastic differential equation. When the difference between the regimes is simply given by a different set of real valued parameters for the drift and diffusion coefficients, with changes between regimes depending only on these parameters, we show that if the delay is known there are consistent estimators for the threshold as long we know how to classify a given observation of the process as belonging to one of the two regimes. When the drift and diffusion coefficients are of geometric Brownian motion type we obtain a model with parameters that can be estimated in a satisfactory way, a model that allows differentiating regimes in some of the NYSE 21 stocks analyzed and also, that gives very satisfactory results when compared to the usual Black–Scholes model for pricing call options.

Regime switching processes are usually defined with an external random source driving the regime changes. In this article, we define and study a regime switching diffusion considering two thresholds, and regime switching occurring, by a change in the diffusion drift and volatility, whenever the trajectory touches the upper threshold after having crossed, or touched, the lower threshold or touches the lower threshold after having crossed, or touched, the upper threshold. We develop an estimation procedure for the thresholds and for the regime parameters of the diffusions. We show that a generalized Black–Scholes model with the regime switching diffusion as the law of the risky asset is arbitrage free and complete under an additional hypothesis on the diffusion coefficients of the two regime diffusions.