Small-Molecule Inhibitors of METTL3, the Major Human Epitranscriptomic Writer

The RNA methylase METTL3 catalyzes the transfer of a methyl group from the cofactor S-adenosyl-L-methionine (SAM) to the N⁶ atom of adenine. We have screened a library of 4000 analogues and derivatives of the adenosine moiety of SAM by high-throughput docking into METTL3. Two series of adenine derivatives were identified in silico, and the binding mode of six of the predicted inhibitors was validated by protein crystallography. Two compounds, one for each series, show good ligand efficiency. We propose a route for their further development into potent and selective inhibitors of METTL3.     

Assessment of extreme and metocean conditions in the Maldives for OTEC applications

The Maldives is a group of tropical atolls, considered globally to be one of the most desirable holiday destinations. There is an urgent requirement to decrease their dependency on fossil fuels that are currently the main source of energy, and a number of renewable energy alternatives are being evaluated. Among these, due to the favorable oceanographic and bathymetric conditions, ocean thermal energy conversion (OTEC) systems represent a viable opportunity for clean and reliable power. However, the stresses the OTEC platform will need to endure during adverse environmental conditions are not well defined. The magnitude of these stresses will then have a direct influence on the design of the OTEC device. In order to overcome this uncertainty, this paper uses hindcast data sets from global weather and ocean models to assess the metocean conditions of the Maldives, with particular reference to extreme conditions. After selecting a suitable location for the deployment of the devices, return values calculated using the peaks‐over‐threshold (POT) methodology are estimated for wind, waves, and currents. The 100‐year return value for the significant wave height is found to be 4.5 m, with a joint occurrence of energy periods between 7.5 and 8.5 seconds, whereas the 100‐year return wind has a velocity of 17.8 m/s and the 100‐year return current of 1.9 m/s. The directionality of these extreme events is also considered, showing the southern and western sub‐quadrants as the prevailing sources, which provides essential information for positioning of the platform. Additional evaluations of tropical revolving storms (TRS) and variations in temperature and salinity patterns are also provided over a 1500‐m water column; temperature varies by approximately 24°C, and salinity by around 2 ppt, showing the suitability of OTEC platforms in the Maldives. This work is therefore of interest to offshore renewable energy stakeholders interested in developing a project in the Maldives or those conducting an analogous analysis in other locations.     

Polylactide latex/nanofibrillated cellulose bionanocomposites of high nanofibrillated cellulose content and nanopaper network structure prepared by a papermaking route

Previous attempts to use polylactide (PLA) latex particles and nanofibrillated cellulose (NFC) in papermaking processing have been limited to low NFC content. In the present study, a bionanocomposite material was successfully produced using a PLA latex and NFC. The components were mixed using a wet mixing method and bionanocomposite films were made by filtration followed by hot pressing. In composite materials, the dispersion of the reinforcing component in the matrix is critical for the material properties. Biopolymers such as PLA are non-polar and soluble only in organic solvents; NFC is, however, highly hydrophilic. By utilizing latex, i.e., an aqueous dispersion of biopolymer micro-particles, wet mixing is possible and the problem of aggregation of the hydrophilic nanocellulose in organic solvent is avoided. The properties of the resulting NFC/PLA latex bionanocomposite films were analyzed. Thorough blending resulted in good dispersion of the reinforcing component within the matrix. Adding increasing amounts of NFC improved the Young's modulus, tensile strength, and strain at break of the bionanocomposite material. The increase in the tensile properties was linear with increasing NFC content as a result of the good dispersion. The NFC also improved the thermal stability of the bionanocomposite material. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Modellbasierte Entscheidungsunterstützung in Produktions- und Dienstleistungsnetzwerken

In this paper, we sketch some of the challenges that should be addressed in future research efforts for model-based decision support in manufacturing and service networks. This includes integration issues, taking into account the autonomy of the decision-making entities in face of information asymmetry, the modeling of preferences of the decision-makers, efficiently determining robust solutions, i.e. solutions that are insensitive with respect to changes in the problem data, and a reduction of the time needed for model building and usage. The problem solution cycle includes problem analysis, the design of appropriate algorithms and their performance assessment. We are interested in a prototypical integration of the proposed methods within application systems, which can be followed up with field tests of the extended application systems. We argue that the described research agenda requires the interdisciplinary collaboration of business and information systems engineering researchers with colleagues from management science, computer science, and operations research. In addition, we present some exemplifying, illustrative examples of relevant research results.     

Integral Equation Method for Evaluation of Eddy-Current Impedance of a Rectangular,Near Surface Crack Inside a Cylindrical Hole

An integral equation method for solving the eddy-current nondestructive evaluation problem of a flat, rectangular, near surface crack inside of a cylindrical hole in a conducting material is presented. The method involves expanding the Green’s tensor, the incoming field, and the jump in electric potential over the crack in suitable basis functions. Here, plane waves, cylindrical waves, and basis functions related to the Chebyshev polynomials, are used. The way of discretization in this method leads to a formulation where the scattering is defined by a scattering matrix, independent of the incoming field. This presents an advantage, when conducting numerical simulations, since the scattering matrix does not have to be recalculated for every probe position. The numerical calculations are straightforward to perform and model predictions are compared with finite element results.     

Engineering a mammalian super producer

Mammalian cells are the preferred host for the manufacture of a wide range of biopharmaceuticals, but production costs are high owing to low productivity. A range of rational engineering strategies have been pursued in order to increase volumetric product titres from mammalian cells, such as delaying apoptosis, manipulation of the cell cycle, and improving metabolism and protein processing. Unfortunately, outcomes from these strategies have been mixed, with few instances where significant improvements in product yield have been achieved. This article reviews and contrasts many of the engineering strategies attempted to date, highlighting the variability and context specificity in outcome. The paper argues that this is a reflection of the complexity of mammalian cells, and that a deeper understanding of the biology underpinning protein production for biotechnological purposes is required. Copyright © 2011 Society of Chemical Industry     

Advancement of an Interferometric Flow Velocity Measurement Technique by Adaptive Optics

Flow measurements often take place under difficult conditions. Optical flow measurement techniques are affected by variations of the refractive index, caused e.g., by temperature, concentration, or pressure gradients. This will give rise to an increased measurement uncertainty or cause the measurement to fail. To overcome these limitations, we propose the employment of adaptive optics. In this contribution we present interferometric flow velocity measurements through a fluctuating air-water interface by the use of adaptive optics. Using the adaptive optics, the rate of valid measurement signals can be improved from 28% to 83%. The results are promising to enable measurements in difficult environments affected by refractive index variations which were not accessible so far.     

Thermobaric stratification in very deep Norwegian freshwater lakes

Thermobaric stratification was investigated in very deep lakes of elongated shape. We considered the spring time configuration when large freshwater lakes may have their deepest recirculation. In five very deep freshwater lakes in Norway, profiles were measured in spring 2006 with multiparameter probes. Temperature profiles confirmed thermobaric stratification in all of these lakes, i.e. the temperature profiles crossed the 4 °C line and thus were affected by pressure effects on the temperature of maximum density. Electrical conductance was low in all of the investigated lakes, and vertical gradients were too small to play a role in the density stratification. In all lakes, deep water was well supplied with oxygen. Three out of five lakes showed a temperature gradient close to Eklund's stability theorem. However, the remaining two lakes clearly opposed the theorem. Bottom temperatures were more closely related to lake length than their maximum depths. Oxygen saturation profiles documented recent intensive gas exchange with the atmosphere. They agree well with the possible formation of deep water from density driven flows at horizontal temperature gradients close to 4 °C.     

Wind energy literature survey no. 29

As a service to readers, Wind Energy regularly conducts literature surveys and publishes lists of relevant articles drawn from recent issues of a large number of periodicals including the following: Journal of Wind Engineering and Industrial Aerodynamics, International Journal of Energy Research, Renewable Energy, Energy Sources, Journal of Solar Energy Engineering, American Institute of Aeronautics and Astronautics Journal and Electric Power Components and Systems along with a number of periodicals published by the Institute of Electrical and Electronics Engineers, etc. The list is limited exclusively to journals not specifically devoted to wind energy and its applications. To assist the reader, the list is separated into broad categories. Although many papers fit several categories, each paper is listed only once under the category thought most appropriate. Please note that the inclusion in the list is not an endorsement of a paper's quality. Please e‐mail any suggestions to corresponding author. Copyright © 2013 John Wiley & Sons, Ltd.