Inhibitors of Mammalian Aquaporin Water Channels

Aquaporins (AQPs) are water channel proteins that are essential to life, being expressed in all kingdoms. In humans, there are 13 AQPs, at least one of which is found in every organ system. The structural biology of the AQP family is well-established and many functions for AQPs have been reported in health and disease. AQP expression is linked to numerous pathologies including tumor metastasis, fluid dysregulation, and traumatic injury. The targeted modulation of AQPs therefore presents an opportunity to develop novel treatments for diverse conditions. Various techniques such as video microscopy, light scattering and fluorescence quenching have been used to test putative AQP inhibitors in both AQP-expressing mammalian cells and heterologous expression systems. The inherent variability within these methods has caused discrepancy and many molecules that are inhibitory in one experimental system (such as tetraethylammonium, acetazolamide, and anti-epileptic drugs) have no activity in others. Some heavy metal ions (that would not be suitable for therapeutic use) and the compound, TGN-020, have been shown to inhibit some AQPs. Clinical trials for neuromyelitis optica treatments using anti-AQP4 IgG are in progress. However, these antibodies have no effect on water transport. More research to standardize high-throughput assays is required to identify AQP modulators for which there is an urgent and unmet clinical need

Stub loaded, low profile UWB antenna with independently controllable notch-bands

The design and realization of a compact coplanar waveguide (CPW) fed ultrawideband (UWB) antenna having dual-notched bands is presented in this article. The antenna possesses on demand notch bands at 4 to 5.78 GHz and 6.83 to 8.22 GHz. The presented design consists of a single iterated octagonal patch antenna designed on cheap FR4 substrate. The stub is utilized to achieve a wide impedance matching of 7.33 GHz (3.2-10.5 GHz), while the notch-bands are realized using split ring circular slots. These notch-bands are controlled independently without affecting the overall performance of the antenna. Simulated and measured results showed that the antenna offers excellent performance with an overall size of 20 × 23 mm2, high efficiency of more than 90%, and a nearly omnidirectional maximum gain of 4.8 dBi. The performance of the proposed antenna is better than the antennas presented in the literature in term of size, stable gain, and independently controllable notch bands. Besides these advantages, the compact size allows the antenna to integrate into small devices easily and help manufacturers to produce a massive number of antennas comfortably

Stub loaded, low profile UWB antenna with independently controllable notch‐bands

The design and realization of a compact coplanar waveguide (CPW) fed ultrawideband (UWB) antenna having dual-notched bands is presented in this article. The antenna possesses on demand notch bands at 4 to 5.78 GHz and 6.83 to 8.22 GHz. The presented design consists of a single iterated octagonal patch antenna designed on cheap FR4 substrate. The stub is utilized to achieve a wide impedance matching of 7.33 GHz (3.2-10.5 GHz), while the notch-bands are realized using split ring circular slots. These notch-bands are controlled independently without affecting the overall performance of the antenna. Simulated and measured results showed that the antenna offers excellent performance with an overall size of 20 × 23 mm2, high efficiency of more than 90%, and a nearly omnidirectional maximum gain of 4.8 dBi. The performance of the proposed antenna is better than the antennas presented in the literature in term of size, stable gain, and independently controllable notch bands. Besides these advantages, the compact size allows the antenna to integrate into small devices easily and help manufacturers to produce a massive number of antennas comfortably

Molecular mechanisms governing aquaporin relocalisation

The aquaporins (AQPs) form a family of integral membrane proteins that facilitate the movement of water across biological membrane by osmosis, as well as facilitating the diffusion of small polar solutes. AQPs have been recognised as drug targets for a variety of disorders associated with disrupted water or solute transport, including brain oedema following stroke or trauma, epilepsy, cancer cell migration and tumour angiogenesis, metabolic disorders, and inflammation. Despite this, drug discovery for AQPs has made little progress due to a lack of reproducible high-throughput assays and difficulties with the druggability of AQP proteins. However, recent studies have suggested that targetting the trafficking of AQP proteins to the plasma membrane is a viable alternative drug target to direct inhibition of the water-conducting pore. Here we review the literature on the trafficking of mammalian AQPs with a view to highlighting potential new drug targets for a variety of conditions associated with disrupted water and solute homeostasis

A Low Profile Ultra-Wideband Antenna with Reconfigurable Notch Band Characteristics for Smart Electronic Systems

This study describes the design and implementation of a small printed ultra-wideband (UWB) antenna for smart electronic systems with on-demand adjustable notching properties. A contiguous sub-band between 3–4.1 GHz, 4.45–6.5 GHz, or for both bands concurrently, can be mitigated by the antenna. Numerous technologies and applications, including WiMAX, Wi-Fi, ISMA, WLAN, and sub-6 GHz, primarily utilize these band segments remitted by the UWB. The upper notch band is implemented by inserting an open-ended stub with the partial ground plane; the lower notch band functionality is obtained by etching a U-shaped slot from the radiating structure. The basic UWB mode is then changed to a UWB mode, with a single or dual notch band, using two diodes to achieve reconfigurability. The antenna has a physically compact size of 17 × 23 mm2 and a quasi-omnidirectional maximum gain of 4.9 dBi, along with a high efficiency of more than 80%, according to both simulation and measurement data. A significant bandwidth in the UWB region is also demonstrated by the proposed design, with a fractional bandwidth of 180% in relation to the 5.2 GHz center frequency. Regarding compactness, consistent gain, and programmable notch features, the proposed antenna outperforms the antennas described in the literature. In addition to these benefits, the antenna’s compact size makes it simple to incorporate into small electronic devices and enables producers to build many antennas without complications