A novel phase shifting cell design is presented for microstrip reflectarrays. It uses a multiscale concept that consists of adaptively modifying the cell size over the reflectarray. A 1563deg phase ...range is demonstrated. A Ku-band reflectarray is manufactured and measured.
In this paper, the new multistructure fast computation technique based on the method of moments (MoM) is applied to the optimization of printed structures with a genetic algorithm. Simultaneous ...analysis of different structures with the new technique leads to important time savings in comparison to an equivalent direct MoM implementation. Several structures with nonintuitive shapes are fabricated and tested. Numerical and technological sensitivities for the different realized structures are compared. The bandwidth optimization of an antenna fed by electromagnetic coupling with a microstrip line is also presented. Excellent agreement between numerical and measured results is observed.
A classic synthetic issue that remains unresolved is the reaction that involves the control of N- versus O-alkylation of ambident anions. This common chemical transformation is important for ...medicinal chemists, who require predictable and reliable protocols for the rapid synthesis of inhibitors. The uncertainty of whether the product(s) are N- and/or O-alkylated is common and can be costly if undetermined. Herein, we report an NMR-based strategy that focuses on distinguishing inhibitors and intermediates that are N- or O-alkylated. The NMR strategy involves three independent and complementary methods. However, any combination of two of the methods can be reliable if the third were compromised due to resonance overlap or other issues. The timely nature of these methods (HSQC/HMQC, HMBC. ROESY, and 13C shift predictions) allows for contemporaneous determination of regioselective alkylation as needed during the optimization of synthetic routes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Combinations of direct acting antivirals (DAAs) that have the potential to suppress emergence of resistant virus and that can be used in interferon-sparing regimens represent a preferred option for ...the treatment of chronic HCV infection. We have discovered allosteric (thumb pocket 1) non-nucleoside inhibitors of HCV NS5B polymerase that inhibit replication in replicon systems. Herein, we report the late-stage optimization of indole-based inhibitors, which began with the identification of a metabolic liability common to many previously reported inhibitors in this series. By use of parallel synthesis techniques, a sparse matrix of inhibitors was generated that provided a collection of inhibitors satisfying potency criteria and displaying improved in vitro ADME profiles. “Cassette” screening for oral absorption in rat provided a short list of potential development candidates. Further evaluation led to the discovery of the first thumb pocket 1 NS5B inhibitor (BILB 1941) that demonstrated antiviral activity in patients chronically infected with genotype 1 HCV.
A new, finite-difference, time-domain (FDTD) multi-resolution strategy for surrounded antenna analysis is presented. The dual-grid, FDTD (DG-FDTD) is divided into two FDTD simulations using different ...grids. Indeed, the antenna is firstly simulated without its environment using a finely discretised FDTD, in order to determine its main characteristics and save its primary radiation. In a second step, this saved field is used as the excitation of a coarse FDTD to simulate the antenna with its environment. The application of the DG-FDTD to an ultra wide-band problem is discussed, and the DG-FDTD turns out to be an accurate and fast tool to simulate various antenna configurations. Furthermore, this method remains stable along the computational time, and is easy to implement in a classical FDTD scheme.
Significant advances have led to receptor induced-fit and conformational selection models for describing bimolecular recognition, but a more comprehensive view must evolve to also include ligand ...shape and conformational changes. Here, we describe an example where a ligand’s “structural hinge” influences potency by inducing an “L-shape” bioactive conformation, and due to its solvent exposure in the complex, reasonable conformation-activity-relationships can be qualitatively attributed. From a ligand design perspective, this feature was exploited by successful linker hopping to an alternate “structural hinge” that led to a new and promising chemical series which matched the ligand bioactive conformation and the pocket bioactive space. Using a combination of X-ray crystallography, NMR and modeling with support from binding-site resistance mutant studies and photoaffinity labeling experiments, we were able to derive inhibitor-polymerase complexes for various chemical series.
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IJS, KILJ, NUK, PNG, UL, UM
A new approach to analyse reflectarray cells is presented, which allows mutual coupling effects to be realistically accounted for by simulating each radiating cell with its actual neighbouring cells, ...either identical or not. The proposed approach is compared to more conventional approaches that consider either an infinite periodic environment or that neglect coupling effects. A comparison between reflectarray measurements and simulations leads to good agreement using the proposed approach.
A new way to carry out numerical cellular telephone simulation in the presence of the head is presented. Here, two finite-difference time-domain (FDTD) simulations with different spatial and time ...resolutions are sequentially combined to perform a dual-grid FDTD (DG-FDTD) simulation. The DG-FDTD approach has the significant advantages to remain stable along the computation and to be easy to implement in a typical FDTD code. When compared with classical FDTD analysis, the DG-FDTD approach exhibits a reduction in computation time and memory requirements by a factor of 2.3 and 3.2, respectively, while providing accurate results both in near-field and far-field radiation.
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