On linear observers and application to fault detection in synchronous generators

This work introduces an observer structure and highlights its distinct advantages in fault detection and isolation. Its application to the issue of shorted turns detection in synchronous generators is demonstrated. For the theoretical foundation, the convergence and design of Luenberger-type observers for disturbed linear time-invariant （LTI） single-input single-output （SISO） systems are reviewed with a particular focus on input and output disturbances. As an additional result, a simple observer design for stationary output disturbances that avoids a system order extension, as in classical results, is proposed.     

Poly(ether sulfone) hollow fiber membranes prepared via nonsolvent-induced phase separation using the green solvent Agnique® AMD 3 L

In recent years, the development of sustainable membrane manufacturing processes by the use of environmentally friendly solvents has become a considerable challenge. In this work, poly(ether sulfone) (PES) hollow fiber membranes were manufactured by the nonsolvent-induced phase separation (NIPS) using the green solvent Agnique® AMD 3 L (N,N-dimethyl lactamide; AMD) and N-ethyl-2-pyrrolidone (NEP) as a conventional solvent. The effect of the solvent on the dope solution and membrane properties was investigated. The morphology, mechanical characteristics, barrier pore sizes as well as gas and water permeances of the hollow fibers prepared with AMD were evaluated and compared to membranes that were similarly prepared using NEP as solvent. Membranes prepared with AMD as polymer solvent and NEP as bore liquid exhibit the largest barrier pore size among all variations. Thus, highest water permeance of 406.9 ± 37.4 kg m⁻² h⁻¹ bar⁻¹ was obtained with this combination. Whereas AMD as sole solvent in membrane preparation decreases membrane permeances caused by a denser membrane structure. Nevertheless, AMD is a promising solvent for a sustainable membrane fabrication providing membrane properties that are competitive with membranes manufactured using the conventional solvent NEP.     

Novel Insights into Guide RNA 5′-Nucleoside/Tide Binding by Human Argonaute 2

The human Argonaute 2 (hAgo2) protein is a key player of RNA interference (RNAi). Upon complex formation with small non-coding RNAs, the protein initially interacts with the 5′-end of a given guide RNA through multiple interactions within the MID domain. This interaction has been reported to show a strong bias for U and A over C and G at the 5′-position. Performing molecular dynamics simulations of binary hAgo2/OH–guide–RNA complexes, we show that hAgo2 is a highly flexible protein capable of binding to guide strands with all four possible 5′-bases. Especially, in the case of C and G this is associated with rather large individual conformational rearrangements affecting the MID, PAZ and even the N-terminal domains to different degrees. Moreover, a 5′-G induces domain motions in the protein, which trigger a previously unreported interaction between the 5′-base and the L2 linker domain. Combining our in silico analyses with biochemical studies of recombinant hAgo2, we find that, contrary to previous observations, hAgo2 is capable of functionally accommodating guide strands regardless of the 5′-base.     

Identification of Highly Potent Protein Kinase C‐Related Kinase 1 Inhibitors by Virtual Screening,Binding Free Energy Rescoring,and in vitro Testing

Despite the considerable interest in protein kinase C‐related kinase 1 (PRK1) as a target in cancer research, there is still a lack of PRK1 inhibitors with suitable selectivity profiles and physicochemical properties. To identify new PRK1 inhibitors we applied a virtual screening approach, which combines ensemble docking, minimization of the protein–ligand complex, binding free energy calculations, and application of quantitative structure–activity relationship (QSAR) models for predicting in vitro activity. The developed approach was then applied in a prospective manner to screen available libraries of kinase inhibitors from Selleck and GlaxoSmithKline (GSK). Compounds that showed favorable prediction were then tested in vitro for PRK1 inhibition. Some of the hits were found to inhibit PRK1 in the low‐nanomolar range. Three in vitro hits were additionally tested in a mass‐spectrometry‐based cellular kinase profiling assay to examine selectivity. Our findings show that nanomolar and drug‐like inhibitors can be identified by the virtual screening approach presented herein. The identified inhibitors are valuable tools for gaining a better understanding of PRK1 inhibition, and the identified hits can serve as starting points for further chemical optimization.     

Deciphering Specificity Determinants for FR900359‐Derived Gqα Inhibitors Based on Computational and Structure–Activity Studies

Direct targeting of intracellular Gα subunits of G protein‐coupled receptors by chemical tools is a challenging task in current pharmacological studies and in the development of novel therapeutic approaches. In this study we analyzed novel FR900359‐based analogs from natural sources, synthetic cyclic peptides, as well as all so‐far known G_qα inhibitors in a comprehensive study to devise a strategy for the elucidation of characteristics that determine interactions with and inhibition of G_q in the specific FR/YM‐binding pocket. Using 2D NMR spectroscopy and molecular docking we identified unique features in the macrocyclic structures responsible for binding to the target protein correlating with inhibitory activity. While all novel compounds were devoid of effects on G_i and G_s proteins, no inhibitor surpassed the biological activity of FR. This raises the question of whether depsipeptides such as FR already represent valuable chemical tools for specific inhibition of G_q and, at the same time, are suitable natural lead structures for the development of novel compounds to target Gα subunits other than G_q.     

Rheological Characterization of Anaerobic Sludge from Agricultural and Bio‐Waste Biogas Plants

Anaerobic sludges taken from 16 different biogas plants were analyzed with respect to their rheological characteristics. All sludges showed temperature‐dependent shear‐thinning behavior with viscosities from 900 – 6000 mPa s at 20 °C. Nevertheless, the liquid fraction of the anaerobic sludges also revealed temperature‐dependent, shear‐thinning behavior with viscosities well above water viscosity (2 – 40 mPa s at 20 °C). The rheological behavior of the liquid phase could be linked to organic fractions, i.e., proteins and polysaccharides. Shear‐thinning and temperature‐dependent behavior was modeled by the power‐law equation and the Arrhenius law, respectively.     

On Eulerian extensions and their application to no-wait flowshop scheduling

We consider a variant of no-wait flowshop scheduling that is motivated by continuous casting in the multistage production process in steel manufacturing. The task is to find a feasible schedule with a minimum number of interruptions, i.e., continuous idle time intervals on the last production stage. Based on an interpretation as Eulerian Extension Problems, we fully settle the complexity status of any particular problem case: We give a very intuitive optimal algorithm for scheduling on two processing stages with one machine in the first stage, and we show that all other problem variants are strongly NP-hard. We also discuss alternative idle time related scheduling models and their justification in the considered steel manufacturing environment. Here, we derive constant factor approximations.     

Representation Theorems for Analytic Machines and Computability of Analytic Functions

We present results concerning analytic machines, a model of real computation introduced by Hotz which extends the well-known Blum, Shub and Smale machines (BSS machines) by infinite converging computations. The well-known representation theorem for BSS machines elucidates the structure of the functions computable in the BSS model: the domain of such a function partitions into countably many semi-algebraic sets, and on each of those sets the function is a polynomial resp. rational function. In this paper, we study whether the representation theorem can, in the univariate case, be extended to analytic machines, i.e. whether functions computable by analytic machines can be represented by power series in some part of their domain. We show that this question can be answered in the negative over the real numbers but positive under certain restrictions for functions over the complex numbers. We then use the machine model to define computability of univariate complex analytic (i.e. holomorphic) functions and examine in particular the class of analytic functions which have analytically computable power series expansions. We show that this class is closed under the basic analytic operations composition, local inversion and analytic continuation.     

Robotic Assembly Processes as a Driver in Architectural Design

Over the last couple of years industrial robots have increasingly gained the interest of architects and designers. Robotics in architecture and construction has mainly been looked at from an engineering perspective during the latter half of the twentieth century, with the main purpose of automating the building process. Today the focus has turned towards realizing non-standardized designs and developing custom fabrication processes. However, the specific characteristics of the robot, which distinguish it from common computer numerically controlled machines, are often overlooked. Industrial robots are universal fabrication machines that lend themselves especially well to assembly tasks. Applied to architecture this resolves to the ability to control and manipulate the building process. As such, applying industrial robots emphasizes construction as an integral part of architectural design. Moreover, designing and manipulating robotic assembly processes can become a driver in architectural design. The potential of such an approach is discussed on the basis of several design experiments that illustrate that by applying such methods, form is not derived from computation or geometry, but from a physical process.