Discovery of TUG-770: a highly potent free fatty acid receptor 1 (FFA1/GPR40) agonist for treatment of type 2 diabetes

Free fatty acid receptor 1 (FFA1 or GPR40) enhances glucose-stimulated insulin secretion from pancreatic β-cells and currently attracts high interest as a new target for the treatment of type 2 diabetes. We here report the discovery of a highly potent FFA1 agonist with favorable physicochemical and pharmacokinetic properties. The compound efficiently normalizes glucose tolerance in diet-induced obese mice, an effect that is fully sustained after 29 days of chronic dosing

Topological Insulators by Topology Optimization

An acoustic topological insulator (TI) is synthesized using topology optimization, a free material inverse design method. The TI appears spontaneously from the optimization process without imposing requirements on the existence of pseudo spin-1/2 states at the TI interface edge, or the Chern number of the topological phases. The resulting TI is passive; consisting of acoustically hard members placed in an air background and has an operational bandwidth of $\approx$12.5\% showing high transmission. Further analysis demonstrates confinement of more than 99\% of the total field intensity in the TI within at most six lattice constants from the TI interface. The proposed design hereby outperforms a reference from recent literature regarding energy transmission, field confinement and operational bandwidth.Comment: 6 pages, 5 figure

Gamma-ray absorption in the microquasar SS433

We discuss the gamma-ray absorption in the inner region of the microquasar SS433. Our investigation includes several contributions to the opacity of this system. They result from the ambient fields generated by the primary star, possibly an A-type supergiant, and a very extended disk around the black hole. Besides the sharp and dramatic absorption effect that occurs every time the star crosses the emission zone, we find in the UV photon field from the extended disk an important source of absorption for very high energy gamma-rays. This results in periodic gamma-ray observational signatures.Comment: 8 pages, 9 figures, to appear in Astropart.Phy

Designing Photonic Topological Insulators with Quantum-Spin-Hall Edge States using Topology Optimization

Designing photonic topological insulators is highly non-trivial because it requires inversion of band symmetries around the band gap, which was so far done using intuition combined with meticulous trial and error. Here we take a completely different approach: we consider the design of photonic topological insulators as an inverse design problem and use topology optimization to maximize the transmission through an edge mode with a sharp bend. Two design domains composed of two different, but initially identical, C$_\text{6v}$-symmetric unit cells define the geometrical design problem. Remarkably, the optimization results in a photonic topological insulator reminiscent of the shrink-and-grow approach to quantum-spin-Hall photonic topological insulators but with notable differences in the topology of the crystal as well as qualitatively different band structures and with significantly improved performance as gauged by the band-gap sizes, which are at least 50 \% larger than previous designs. Furthermore, we find a directional beta factor exceeding 99 \%, and very low losses for sharp bends. Our approach allows for the introduction of fabrication limitations by design and opens an avenue towards designing PTIs with hitherto unexplored symmetry constraints.Comment: 7 pages, 5 figure

The RD53 Collaboration's SystemVerilog-UVM Simulation Framework and its General Applicability to Design of Advanced Pixel Readout Chips

The foreseen Phase 2 pixel upgrades at the LHC have very challenging requirements for the design of hybrid pixel readout chips. A versatile pixel simulation platform is as an essential development tool for the design, verification and optimization of both the system architecture and the pixel chip building blocks (Intellectual Properties, IPs). This work is focused on the implemented simulation and verification environment named VEPIX53, built using the SystemVerilog language and the Universal Verification Methodology (UVM) class library in the framework of the RD53 Collaboration. The environment supports pixel chips at different levels of description: its reusable components feature the generation of different classes of parameterized input hits to the pixel matrix, monitoring of pixel chip inputs and outputs, conformity checks between predicted and actual outputs and collection of statistics on system performance. The environment has been tested performing a study of shared architectures of the trigger latency buffering section of pixel chips. A fully shared architecture and a distributed one have been described at behavioral level and simulated; the resulting memory occupancy statistics and hit loss rates have subsequently been compared.Comment: 15 pages, 10 figures (11 figure files), submitted to Journal of Instrumentatio

Derivation of diagnostic models based on formalized process knowledge

© IFAC.Industrial systems are vulnerable to faults. Early and accurate detection and diagnosis in production systems can minimize down-time, increase the safety of the plant operation, and reduce manufacturing costs. Knowledge- and model-based approaches to automated fault detection and diagnosis have been demonstrated to be suitable for fault cause analysis within a broad range of industrial processes and research case studies. However, the implementation of these methods demands a complex and error-prone development phase, especially due to the extensive efforts required during the derivation of models and their respective validation. In an effort to reduce such modeling complexity, this paper presents a structured causal modeling approach to supporting the derivation of diagnostic models based on formalized process knowledge. The method described herein exploits the Formalized Process Description Guideline VDI/VDE 3682 to establish causal relations among key-process variables, develops an extension of the Signed Digraph model combined with the use of fuzzy set theory to allow more accurate causality descriptions, and proposes a representation of the resulting diagnostic model in CAEX/AutomationML targeting dynamic data access, portability, and seamless information exchange

Clarina Howard Nichols: A rhetorical criticism of selected speeches

Thesis (M.A.)--University of Kansas, Communication Studies, 1987