Compact Broadband Circularly Polarized CPW-Fed Antenna with Characteristic Mode Analysis

A compact circularly polarized (CP) antenna is proposed for low-profile and wideband operation based on characteristic mode analysis (CMA). A ring patch with a gap and two arc-shaped metallic stubs as the radiator is analyzed and optimized by CMA to figure out the orthogonal modes and operating frequency band for potential good axial ratio (AR) performance. The studies of these CP modes provide a physical insight into the property of broadband circular polarization. Such an in-depth understanding paves the way for the proposal of novel CP antenna with separation between the design of radiator and feeding network. A 50-Ω coplanar waveguide (CPW) is introduced and placed appropriately to excite the desired modes based on the information from CMA, which employs two asymmetric ground planes to improve the performance in terms of AR and impedance matching. The antenna with a compact size of 0.71λ0 × 0.76λ0 × 0.038λ0 (λ0 is the free-space wavelength at the center frequency of the 3-dB AR bandwidth) is fabricated and measured for validation. The realized gain varies from 1.6 to 3.1 dBic over the operating bandwidth characterized by the measured 10-dB impedance bandwidth of 83.8% (3.98–9.72 GHz) and 3-dB AR bandwidth of 70.3% (4.59–9.57 GHz), respectively.

Resistance to microtubule-stabilising agents following point mutation of human βI-tubulin

<p>Marine environments represent a rich source of bioactive secondary metabolites that may be harnessed for use in a therapeutic context. Two novel compounds, peloruside A and laulimalide, isolated from the marine sponges Mycale hentsheli and Cacospongia mycofijiensis, respectively, both demonstrate useful pharmacological properties in mammalian cells. These compounds share major similarities with microtubule-stabilising agents. Like other agents in this class, peloruside A and laulimalide bind to the β-tubulin subunit of microtubules, the primary cytoskeletal element of eukaryotic cells. These compounds enhance polymerisation dynamics between ternary microtubule structures and severely hinder necessary cytoskeletal rearrangements within the cell. Over the course of a patient’s treatment, cancerous cells may develop multi-drug resistance phenotypes. P-glycoprotein drug efflux pumps play a major role in the development of therapy resistance in many cancers, as the current generation microtubule-stabilising agents are easily removed from diseased cells by upregulated efflux mechanisms. Unlike agents already in clinical application, both peloruside A and laulimalide are poor substrates for removal by these mechanisms, making them and their synthetic derivatives interesting as potential treatments for drug-resistant tumours. Peloruside A and laulimalide exhibit potent nanomolar anti-mitotic activities in vitro and arrest cell cycle progression in G₂/M phase, leading to cell death – a characteristic mode of action among microtubule-stabilising agents. Unlike all known agents in this class, peloruside A and laulimalide share a secondary, unique binding region in β-tubulin. In the past decade our understanding of this region has developed, revealing a second, unique mechanism for stabilisation of microtubules. Using mammalian cells to model physiological tubulin, the present study investigates the predicted role of aspartic acid 297 of human βI-tubulin in the binding association of both peloruside A and laulimalide. This particular amino acid is predicted to hydrogen bond with both compounds, contributing to their activity as stabilisers. It was revealed that the introduction of a point mutation in D297 resulted in a small but highly consistent resistance phenotype to both compounds, but not to microtubule-stabilising agents that bind to the traditional, taxoid site on β-tubulin. It was concluded that aspartic acid 297 is likely to be one of the amino acids directly involved in the binding association of peloruside A and laulimalide to β-tubulin, contributing partial compound stabilisation. The rational synthesis of future analogues may benefit from these findings in the design of molecules with enhanced interactions at this particular amino acid residue.</p>